bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Effects of Blood Metabolites and Obstructive Sleep Apnea: A
Mendelian Randomization Study
Authors: Wu Jing-Hao , Yang Ying-Hao , Wang Yun-Chao , Yu Wen-Kai , Li Shan-Shan , Mei Yun-Yun , Ce-Zong  , Zhou Zi-Han , Zhu Hang-Hang , He Liu-Chang , Li Xin-Yu , Shi Chang-He , Li Yu-Sheng 
Published: December 2023

Background:
Obstructive sleep apnea (OSA) is one of the most common forms of
sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important
role in the pathophysiology of OSA. However, the causal relationship between these metabolites
and OSA remains unclear.

Aims:
We use a mendelian randomization (MR) approach to investigate the causal associations
between the genetic liability to metabolites and OSA.

Methods:
We performed a 2-sample inverse-variance weighted mendelian randomization analysis
to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity
analyses were performed to assess pleiotropy. We used multivariate mendelian randomization
analyses to assess confounding factors and mendelian randomization Bayesian model averaging to
rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway
analysis to identify potential metabolic pathways.

Results:
We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12
unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids(
1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate,
Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3),
3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins
[Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also
identified several metabolic pathways that involved in the pathogenesis of OSA.

Conclusion:
MR (mendelian randomization) approach was performed to identify 6 protective factors
and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant
risk factors for OSA. Our study also confirmed several significant metabolic pathways that were
involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways
were the most significant metabolic pathways that were involved in the pathogenesis of
OSA.
In Silico Screening of Some Active Phytochemicals to Identify Promising
Inhibitors Against SARS-CoV-2 Targets
Authors: Alagarsamy V. , Solomon V. Raja , Murugesan S. , Sundar P. Shyam , Muzaffar-Ur-Rehman MD. , Chandu A. , Aishwarya A. Dharshini , Narendhar B. , Sulthana M.T. , Ravikumar V. 
Published: December 2023

Background:
There are very few small-molecule drug candidates developed against
SARS-CoV-2 that have been revealed since the epidemic began in November 2019. The typical
medicinal chemistry discovery approach requires more than a decade of the year of painstaking research
and development and a significant financial guarantee, which is not feasible in the challenge
of the current epidemic.

Objective:
This current study proposes to find and identify the most effective and promising phytomolecules
against SARS-CoV-2 in six essential proteins (3CL protease, Main protease, Papain-
Like protease, N-protein RNA binding domain, RNA-dependent RNA polymerase, and Spike receptor
binding domain target through in silico screening of 63 phytomolecules from six different
Ayurveda medicinal plants.

Methods:
The phytomolecules and SARS-CoV-2 proteins were taken from public domain databases
such as PubChem and RCSB Protein Data Bank. For in silico screening, the molecular interactions,
binding energy, and ADMET properties were investigated.

Results:
The structure-based molecular docking reveals some molecules' greater affinity towards
the target than the co-crystal ligand. Our results show that tannic acid, cyanidin-3-rutinoside, zeaxanthin,
and carbolactone are phytomolecules capable of inhibiting SARS-CoV-2 target proteins
in the least energy conformations. Tannic acid had the least binding energy of -8.8 kcal/mol, which
is better than the binding energy of its corresponding co-crystal ligand (-7.5 kcal/mol) against 3 CL
protease. Also, it has shown the least binding energy of -9.9 kcal/mol with a more significant number
of conventional hydrogen bond interactions against the RdRp target. Cyanidin-3-rutinoside
showed binding energy values of -8.8 and -7.6 kcal/mol against Main protease and Papain-like protease,
respectively. Zeaxanthin was the top candidate in the N protein RBD with a binding score of -
8.4 kcal/mol, which is slightly better when compared to a co-crystal ligand (-8.2 kcal/mol). In the
spike, carbolactone was the suitable candidate with the binding energy of -7.2 kcal/mol and formed
a conventional hydrogen bond and two hydrophobic interactions. The best binding affinity-scored
phytomolecules were selected for the MD simulations studies.

Conclusion:
The present in silico screening study suggested that active phytomolecules from medicinal
plants could inhibit SARS-CoV-2 targets. The elite docked compounds with drug-like properties
have a harmless ADMET profile, which may help to develop promising COVID-19 inhibitors.
An Insight into Different Experimental Models used for Hepatoprotective
Studies: A Review
Authors: Babu Sucharita , Ranajit Santosh K , Pattnaik Gurudutta , Ghosh Goutam , Rath Goutam , Kar Biswakanth 
Published: December 2023

Abstract:
Numerous factors, including exposure to harmful substances, drinking too much alcohol,
contracting certain hepatitis serotypes, and using specific medicines, contribute to the development
of liver illnesses. Lipid peroxidation and other forms of oxidative stress are the main mechanisms by
which hepatotoxic substances harm liver cells. Pathological changes in the liver include a rise in the
levels of blood serum, a decrease in antioxidant enzymes, as well as the formation of free radical
radicals. It is necessary to find pharmaceutical alternatives to treat liver diseases to increase their
efficacy and decrease their toxicity. For the development of new therapeutic medications, a greater
knowledge of primary mechanisms is required. In order to mimic human liver diseases, animal models are developed. Animal models have been used for several decades to study the pathogenesis of
liver disorders and related toxicities. For many years, animal models have been utilized to investigate
the pathophysiology of liver illness and associated toxicity. The animal models are created to imitate
human hepatic disorders. This review enlisted numerous hepatic damage in vitro and in vivo models
using various toxicants, their probable biochemical pathways and numerous metabolic pathways via
oxidative stressors, different serum biomarkers enzymes are discussed, which will help to identify
the most accurate and suitable model to test any plant preparations to check and evaluate their hepatoprotective properties.
A Critical Sojourn of Hyaluronic Acid-based Hydrogels in the Wound Healing Process: Current Advances and Future Prospects
Authors: Markandeywar Tanmay Sudhakar , Singh Dilpreet , Narang Raj Kumar 
Published: December 2023

Abstract:"Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG), is a significant component of the epidermal extracellular matrix (ECM). It plays multiple roles in the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. Due to its inherent characteristics, including non-immunoreactivity, exceptional biocompatibility, biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity, HA has found applications in the production of wound dressings. HA's synergistic role in enhancing deeper penetration into chronic wounds and its biofunctional properties in the healing process have been harnessed. HA-based wound dressings, often incorporating biomolecules or drugs to improve the dressing's biochemical performance during wound healing, have been developed. In this review, we explore the current state of knowledge regarding hydrogels based on HA, focusing on their biofunctional properties and delivery mechanisms. We present the latest developments in the research and development of HA-based hydrogels for the treatment of skin wounds."
Multisystem Inflammatory Syndrome in Children (MIS-C) in a
Low-income Country: What Treatment Should be Adopted in Case
of a Lack of Immunoglobulin?
Authors: Abdeladim Babakhouya , Massilia Bouhmidi , Aziza Elouali , Zohair Elhaddar , Ayad Ghanam , Maria Rkain 
Published: December 2023

Introduction:
In multisystem inflammatory syndrome (MIS-C), children typically
present high-grade fever, gastrointestinal symptoms, Kawasaki-like symptoms, and even a toxic
shock-like syndrome days to weeks after recovering from SARS-CoV-2 infection. It is important
to raise awareness of this condition in order to have early diagnosis and immediate treatment of
patients. We have, herein, reported 44 cases of MIS-C with various risk factors and symptoms.
Furthermore, we have emphasized the efficacy of experience in treating children with MIS-C
with high-dose corticosteroids as an alternative to immunoglobulin in low-income countries.

Methods:
We conducted a targeted survey of MIS-C from early May 2020 to October 2022 on
44 children and adolescents with characteristics of multisystem inflammatory syndrome admitted
to the pediatric department of the university hospital center in Oujda, Morocco, to which patients
diagnosed with MIS-C were referred. The case definition included six criteria: serious illness
leading to hospitalization, age under 18 years, fever of at least 24 hours, laboratory evidence of
inflammation, multi-organ involvement, biological inflammatory syndrome, and evidence of
coronavirus infection based on polymerase chain reaction, antibody testing or exposure to people
with COVID-19 in the past month. The criteria used to diagnose myocarditis were impaired left
ventricular function, central mitral leak, and elevation of BNP or pro-BNP. Coronary
involvement was assessed by the z-score and the criteria for its presence was a z-score equal to
or greater than 2.5.

Results:
Our study included 44 children and adolescents with MIS-C in our hospital, with male
predominance (79%) and a median age of six years. Cardiovascular involvement was present in
91%, mucocutaneous in 78%, gastrointestinal in 70%, hematologic in 84%, and respiratory in
2% of patients. Coronary abnormalities (z-score ≥ 2.5) were documented in 21 cases (48%).
Glucocorticoids were frequently used in comparison to immunoglobulin, which were
uncommonly available and expensive.

Conclusion:
The therapeutic protocol that was adopted was high doses of short-term prednisone
(Cortancyl) at 4mg/kg/day for 4 days. Favorable outcome was noted in all patients over a 2-year
period.
Screening and Identification of ESR1 as a Target of Icaritin in Hepatocellular
Carcinoma: Evidence from Bibliometrics and Bioinformatic Analysis
Authors: Zhou Yinghui , Gu Jia , Yu Huiying , Chen Fengyang , Long Chao , Maihemuti Maiweilan , Chen Tingsong , Zhang Wei 
Published: December 2023

Background::
In 2022, icaritin a Traditional Chinese Medicine with estrogen-like activities was recommended by the CSCO guidelines as a systematic treatment
for patients with advanced HCC due to its clinical safety and efficacy. However the mechanism and targets of icaritin are unclear. In this study we
aimed to reveal the target of icaritin in HCC

Methods::
First literature related to icaritin was downloaded from the Web of Science. The software programs “Rstudio” “VOSviewer” and “Mendeley
Desktop” were used to analyze the distribution of icaritin publications and research hotspots. Meanwhile icaritin-related genes were obtained by
combining them with the PubChem database. Second transcriptome data of HCC patients were obtained from the TCGA database. The proteinprotein
interaction (PPI) analysis of icaritin-related genes was performed using the String data platform and the visualization and network topology
analysis were performed using Cytoscape. Cox regression analyses were combined to screen the hub target and verified it through cell experiments.

Results::
A total of 239 icaritin-related articles were obtained HCC is a new hotspot in the icaritin field. 292 icaritin-related genes were obtained and a core
module containing 34 genes was obtained by module division. Among them ESR1 was an independent prognostic factor. Molecular docking
showed that ESR1 and icaritin had a high affinity. Functional studies revealed that ESR1 inhibits HCC cell malignant proliferation and improves
the sensitivity of HCC cells to icaritin.

Conclusion::
We propose that ESR1 as a target of icaritin may be conducive to improving icaritin therapy.
New Drug for Management of Severe Uncontrolled Asthma: Tezepelumab
Authors: Sharma Manvi , George Prince P. , Kumar Ranjeet , Sharma Amit 
Published: December 2023

Abstract:
Tezepelumab is a first-in-class human IgG2λ monoclonal antibody used to treat severe, uncontrolled asthma. Tezepelumab acts by hindering the
action of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine that triggers an immunological response by binding to TSLP and
thereby preventing its binding with the TSLP receptor complex. TSLP has a critical role in Th2 immunity and plays an important role in the
pathogenesis of asthma because it stimulates the production of Th2-associated inflammatory mediators, such as interleukin-4, interleukin-5,
interleukin-9, and interleukin-13. It is the first biologic with no phenotypic or biomarker restrictions that has been approved for use in severe
asthma. Tezepelumab is indicated in severe, uncontrolled asthma patients due to its safety, tolerability, and efficacy. Adults with severe,
uncontrolled asthma experienced considerably lower annualised asthma exacerbation rates (AAERs) when administered with tezepelumab
compared to a placebo. These preliminary results indicated that the TSLP-induced release of T2 inflammatory mediators may be reduced, and the
sustained inhibition was maintained over a 52-week treatment period. In this review, we have summarised various phase III clinical trials and the
mechanism of action of tezepelumab in severe, uncontrolled asthma.
Synthesis and Anti TB Screening of α-Acyloxy Carboxamides via Passerini MCRs Prompted by GaCl3 and PEG-400 Media
Authors: Piludiya Reshmabanu I. , Sriram Dharmarajan , Kumari Jyothi , Kapadiya Khushal M. 
Published: December 2023

Aims:
The Isocyanides based Multi-component reactions (IMCRs), and Passerini reactions were performed by using GaCl3 and PEG-400 media to generate a library of new scaffolds.

Background:
The Isocyanides Multi-component reactions (IMCRs) have proven their importance due to their major advantages in synthetic and medicinal areas. Among various IMCRs, Passerini stands for their pertinency in the novel adducts articulation and generates an amide functionality which shows unbeatable efficiency towards the generation of lead scaffolds. In the research fields, PEG is acting as a versatile greener solvent due to its beneficial economic advantages. In general, chiral-based separation is always a headache for the chemist and researchers tend to generate routes with major products such as single isomers. Most MCRs studied with metal-based synthesis and rather use Au or Pt-based catalyst, Gallium that has been widely explored in chiral Lewis acid catalysis, organo-catalysis, or cooperative catalysis to generate a library of compounds with high stereoselectivity with mild reaction conditions.

Objective:
To find diverse scaffolds in the field of organic chemistry using easily accessible metal catalysts.

Methods:
In this article, Enantiomerically pure, 2-(((1H-benzo[d][1,2,3]triazol-1-yl)methyl)amino)-2-oxo-1-substitutedphenylethyl pyrazine-2-carboxylate (4a-4j), produced through a three-component passerine coupling reaction under GaCl3 as a Lewis acid-promoted conditions with diastereose-letivity ranging from moderate to good.

Results:
The designed approach exhibited an in situ single-step-economical path to enantiomerically pure, α-acyloxy carboxamides with pyrazine and 1H-benzo[d][1,2,3]triazole fragments employing the greener way of media through “PEG-400”. In an anti-TB screening against H37Rv, the withdrawing groups showed excellent activity compared to the donating groups

Conclusion:
It was expected that the Lewis acid-PEG pairs could serve as the best catalytic transfor-mations in eco-friendly ways and enrich the pure enantiomer of the adduct. On the medicinal side, the isolated library of compounds was screened for their biological activity against “Mycobacterium Tubercu-losis H37Rv” and 4f featuring “4-F” as a substituent was found to be most active [MIC: 12.5 μg/mL].
Nanosuspension as a Novel Nanovehicle for Drug Delivery: A Recent
Update on Patents and Therapeutic Applications
Authors: Rani Asha , Verma Ravinder , Kumar Manish , Tiwari Abhishek , Tiwari Varsha , Bhatt Shailendra , Mittal Vineet , Kaushik Deepak 
Published: December 2023

Abstract:
Solubility is a critical factor for the therapeutic action of drugs and does not depend on the administration of routes. Various conventional methods are used to enhance the solubility of the drug, which show limited applicability. Nanotechnology is used to improve the solubility and bioavailability of drugs that belong to BCS classes II and IV. Nanosuspension is the dispersion of pure drug nanoparticles in aqueous with a minimum amount of surfactant, stabilizing the formula-tion. Various techniques, such as the bottom-up approach, dissocubes, nanopure, nanoedge, nano-jet process, supercritical fluid, dry co-grinding, milling media, and nanoprecipitation, have been used to formulate nanosuspension. Nanosuspension can be administered orally, inhalation, trans-dermal, ocular, injectable, topical, and pulmonary. To resolve the problem of solubility and stabil-ity, nanosuspension has received much attention because of its technical simplicity, cost-effectiveness, and ease of significant scale-up. Nanosuspension can control particle size surface charge properties and release the drug at specific sites at an optimal rate. Recently, more than 100 patents have been published on nanosuspension. This review article covers the different prepara-tion methods, formulation composition, marketed products, characterization, and recent patents on nanosuspension. The various benefits and evaluation of the parameters of nanosuspension are discussed briefly. This patent-based review will enhance the knowledge of control drug delivery and related patents on nanosuspension.
Nanotechnological Carriers in the Treatment of Cancer: A Review
Authors: Gautam Darsh , Talwan Poonam , Kumar Sanjay , Joshi Gaurav , Singh Ranjit 
Published: December 2023

Abstract:
There is an urgent need of advanced techniques/technologies for the treatment of can-cer as it is becoming the major cause of mortality and morbidity worldwide. The improvement of the cancer drug delivery system has been made possible by the formation of novel nanomaterials and nanocarriers. The nanocarriers prevent rapid degradation of the drug and thereby deliver the drug to a specific tumor site at therapeutic concentrations, meanwhile reducing the adverse/side effects by avoiding the delivery of the drug to normal sites. The antitumor activity can be en-hanced by increasing the tumoral uptake of nanocarriers. By delivering the nanocarriers either by active or passive targeting, the tumoral uptake can be increased. The pharmacokinetics, pharma-codynamics, and safety profile of the drug are determined by structural and physical factors like size, charge, shape, and other surface characteristics, hence the design of the nanoparticles is an important factor. In the present review, the mechanism of cellular targeting, along with the differ-ent nanoparticles used in cancer therapy is discussed. Nanotechnology have gained huge ground due to improved diagnosis and treatment additionally saving the time and resources, which makes this technology to get more landscape for researchers/ oncologists.
Behavior Change Approaches in Digital Technology–Based Physical Rehabilitation Interventions Following Stroke: Scoping Review
Authors: Gooch Helen J , Jarvis Kathryn A , Stockley Rachel C 
Published: December 2023

Background
Digital health technologies (DHTs) are increasingly used in physical stroke rehabilitation to support individuals in successfully engaging with the frequent, intensive, and lengthy activities required to optimize recovery. Despite this, little is known about behavior change within these interventions.

Objective
This scoping review aimed to identify if and how behavior change approaches (ie, theories, models, frameworks, and techniques to influence behavior) are incorporated within physical stroke rehabilitation interventions that include a DHT.

Methods
Databases (Embase, MEDLINE, PsycINFO, CINAHL, Cochrane Library, and AMED) were searched using keywords relating to behavior change, DHT, physical rehabilitation, and stroke. The results were independently screened by 2 reviewers. Sources were included if they reported a completed primary research study in which a behavior change approach could be identified within a physical stroke rehabilitation intervention that included a DHT. Data, including the study design, DHT used, and behavior change approaches, were charted. Specific behavior change techniques were coded to the behavior change technique taxonomy version 1 (BCTTv1).

Results
From a total of 1973 identified sources, 103 (5%) studies were included for data charting. The most common reason for exclusion at full-text screening was the absence of an explicit approach to behavior change (165/245, 67%). Almost half (45/103, 44%) of the included studies were described as pilot or feasibility studies. Virtual reality was the most frequently identified DHT type (58/103, 56%), and almost two-thirds (65/103, 63%) of studies focused on upper limb rehabilitation. Only a limited number of studies (18/103, 17%) included a theory, model, or framework for behavior change. The most frequently used BCTTv1 clusters were feedback and monitoring (88/103, 85%), reward and threat (56/103, 54%), goals and planning (33/103, 32%), and shaping knowledge (33/103, 32%). Relationships between feedback and monitoring and reward and threat were identified using a relationship map, with prominent use of both of these clusters in interventions that included virtual reality.

Conclusions
Despite an assumption that DHTs can promote engagement in rehabilitation, this scoping review demonstrates that very few studies of physical stroke rehabilitation that include a DHT overtly used any form of behavior change approach. From those studies that did consider behavior change, most did not report a robust underpinning theory. Future development and research need to explicitly articulate how including DHTs within an intervention may support the behavior change required for optimal engagement in physical rehabilitation following stroke, as well as establish their effectiveness. This understanding is likely to support the realization of the transformative potential of DHTs in stroke rehabilitation.