bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Updated Review For Hyperuricemia and Gout Management; Special Focus on the Available Drug Delivery Systems and Clinical Trials
Authors: Karantas Ioannis D. , Miliotou Androulla N. , Siafaka Panoraia I. 
Published: August 2023

Background:
Hyperuricemia belongs to metabolic syndromes where increased uric
acid levels are identified in the blood serum. Such a syndrome could be responsible for kidney
stone formation, gout, hypertension, and chronic kidney diseases. It has been reported
that cardiovascular risks have been linked with hyperuricemia. Gout is of the most frequent
manifestations due to hyperuricemia; its management involves various pharmacological available
options and dietary changes. Throughout the literature, various dosage forms are studied
as alternative options to the present drug delivery systems.

Objective:
To update and summarize the current information for gout and hyperuricemia management.

Methods:
Authors have performed a thorough literature research from 2010-2023 using keywords
such as hyperuricemia, gout, diagnosis, guidelines, drug delivery and clinical trials.
The databases used were PubMed, ScienceDirect. According to our inclusion criteria, all
studies which include the previous terms, as well as drugs or other molecules that can be applied
for gout and/or hyperuricemia management, were added.

Results:
In this article, authors have summarized the pathogenesis, diagnosis and updated
guidelines for gout and hyperuricemia management. Moreover, the authors have reviewed
and discussed current drug delivery systems found in the literature, including drugs targeting
the above disorders. Finally, the available clinical trials assessing the efficacy of newer drugs
or combinations of the past ones, are being discussed.

Conclusion:
The available drugs and dosage forms are limited, and therefore, scientific society
should focus on the development of more efficient drug delivery systems for hyperuricemia
and gout management.
Development and Validation of a Simple, Fast, and Accessible HPLC-UV
Method for Cannabinoids Determination in Cannabis sativa L. Extracts and
Medicinal Oils
Authors: Silva Sofrás Fresia Melina , Alonso Rosario , Retta Daiana Sabrina , Di Leo Lira Paola , Desimone Martin Federico , van Baren Catalina María 
Published: August 2023

Introduction:
Cannabis sativa L. is a well-recognized medicinal plant. Cannabis regulations in Argentina
are insufficient to solve the problem of patient access to full-spectrum cannabis-based products. So, the
market of artisanal products with unknown quality and dosage of cannabinoids is increasing, and so is the local
demand and need for analyzing these products. However, much of the latest validated methodologies for cannabinoid
quantification include expensive instrumentation that is not always available in laboratories of health institutions
in Argentina.

Methods:
The aim of this work was to develop and validate a simple and rapid HPLC-UV method for the identification
and quantification of principal cannabinoids in cannabis resins, inflorescences, and medicinal oils using
standard HPLC equipment. The cannabinoids selected for validation were cannabidiol acid (CBDA), cannabigerol
(CBG), cannabidiol (CBD), cannabinol (CBN), delta-9-tetrahydrocannabinol (Δ9-THC), cannabichromene
(CBC), and tetrahydrocannabinol acid (THCA). A method for the simultaneous identification and
quantification of these 7 main cannabinoids was developed and then validated. Some data parameters were comparable
to other reports with more sophisticated analytical instruments for the analysis of cannabis. The assessed
limits of detection and the limits of quantitation ranged from 0.9 to 3.66 μg/mL and 2.78 to 11.09
μg/mL, respectively. The concentration-response relationship of the method indicated a linear relationship between
the concentration and peak area with R2 values of > 0.99 for all 7 cannabinoids.

Results:
The relative standard deviation (RSD%) varied from 2.34 to 4.82 for intraday repeatability and from
1.16 to 3.15 for interday repeatability. The percentage of recovery values was between 94 to 115% (resins) and
80 to 103% (inflorescence extract). The cannabis industry is growing rapidly, and there is a need for reliable
testing methods to ensure the safety and efficacy of cannabis products. In addition, current methods for cannabinoid
analysis are often time-consuming and expensive, while the HPLC-UV method herein reported is a simple,
rapid, accurate, and cost-effective alternative for the analysis of cannabinoids in cannabis resins, inflorescences,
and medicinal oils.

Conclusion:
This method will be proposed to be included in the Cannabis sativa L. monograph of the Argentine
Pharmacopoeia.
High-Throughput Sequencing Technology Assisted Investigation of the
Correlation Between Intestinal Flora, Serum Biochemistry, Blood Lipids,
and Tumour Markers in Patients with Gastric Cancer and Healthy
Plateau Residents
Authors: Zhou Linghong , Wang Bo , Liu Linxun , Han Pei , Ji Li , Zhang Zilong , Zhang Jingni 
Published: August 2023

Aim:
The goal is to use high-throughput sequencing technology to compare and study the structure
and variety of intestinal flora in people with gastric cancer and healthy people in the Qinghai-Tibet Plateau.

Background:
Recent research has connected gut flora structure to numerous disorders. Metabolites,
endotoxins, and immunomodulatory modulation might cause gastrointestinal or other systemic diseases
and affect gastric cancer treatment and prognosis. We used the correlation study to uncover biomarkers
associated with good intestinal flora and gastric cancer groups on the plateau to investigate their involvement
in gastric cancer development.

Objectives:
To investigate the possible links between intestinal flora and gastric cancer in the Qinghai
Plateau region using a variety of clinical phenotypic data and to investigate the flora that may be linked
to gastric cancer.

Methods:
The 22 Qinghai Province tertiary hospital gastric cancer patients and 30 healthy people had
their fresh faeces collected. To examine intestinal flora diversity and composition, 52 patients underwent
16S rDNA high-throughput gene sequencing of intestinal bacteria. The correlation between clinical phenotypes
and the top 15 dominant intestinal flora at the phylum level was analyzed.

Results:
The difference in total protein TP between the healthy group and the gastric cancer group was
statistically significant (P<0.001). Globulin was significantly different (P<0.05), TC of total cholesterol
was significantly different (P<0.05). High-density lipoprotein showed statistical significance
(P<0.05).The difference in low-density lipoprotein was statistically significant (P<0.001). Alphafetoprotein
was significantly different (P<0.05). CA72-4 carbohydrate antigen (P<0.05).

Conclusion:
There were significant differences in total protein, globulin, total cholesterol, high density
lipoprotein, low-density lipoprotein, alpha-fetoprotein and carbohydrate antigen CA72-4 in patients
with gastric cancer in the plateau area compared with the healthy group, and the different clinical variables
were correlated with intestinal flora at some phylum and genus levels.
Anti-Angiogenic Agents Combined with Immunotherapy for Advanced
Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Lin Heng , Ma Chenhui , Zhong Aihong , Zang Huanping , Chen Wenxin , Li Lixiu , Le Yuyin , Xie Qiang 
Published: August 2023

Background:
Anti-angiogenic agents could enhance tumor immunity response, and anti-
angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small
cell lung cancer (NSCLC). The efficacy of this combination therapy remains controversial and obscure.

Aim:
We conducted a meta-analysis to evaluate the clinical efficacy and safety of this therapeutic
strategy in patients with advanced NSCLC and provide more guidance for treating NSCLC clinically.

Methods:
A systematic literature search was performed in PubMed, Embase, Web of Science,
CNKI, and Wanfang databases to identify relevant studies published up to December 2021. The
primary endpoint was the objective response rate (ORR). Second endpoints were progression-free
survival (PFS), overall survival (OS), and grade ≥3 AEs adverse events (AEs). The sensitivity
analysis was conducted to confirm the stability of the results. STATA 15.0 was utilized for all
pooled analyses.

Results:
Eleven studies were eventually included in the meta-analysis, involving 533 patients with
advanced NSCLC. The pooled ORR rate was 27% (95% CI 18% to 35%; I2 =84.2%; p<0.001),
while the pooled median PFS and OS was 5.84 months (95% CI 4.66 to 7.03 months; I2=78.4%;
p<0.001) and 14.20 months (95% CI 11.08 to 17.32 months; I2=82.2%; p=0.001), respectively.
Most common grade ≥3 AEs included hypertension, hand-foot syndrome, diarrhea, adrenal insufficiency,
hyponatremia, proteinuria, rash, thrombocytopenia, and fatigue.

Conclusion:
Anti-angiogenesis combined with immunotherapy demonstrated satisfactory antitumor
activity and an acceptable toxicity profile in patients with advanced NSCLC. The pooled results
of our meta-analysis provided further evidence supporting the favorable efficacy and safety of
this therapeutic strategy.
Comparative Analysis of Pharmacokinetics and Metabolites of Three Main
Terpenoids before and after Compatibility of Frankincense and Myrrh in Rats by
UHPLC-MS
Authors: Fan Ruo-ying , Gao Ru-meng , Li Jia-shang , Su Shu-lan , Shang Er-xin , Qian Da-wei , Duan Jin-ao 
Published: August 2023

Background:
3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the
main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia
8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra-
1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh.

Objective:
In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense,
myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and
provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility in vivo.

Methods:
The area under the blood concentration time curve (AUC), half-life (t1/2) and drug clearance (CL) of
AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in
rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass
spectrometry system (UHPLC-LTQ-Orbitrap-MS).

Results:
The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2
h, 2 h and 15 min, respectively. AUC0-t and t1/2 of the three components increased in varying degrees after compatibility,
and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and
phase II in rats, and there represented differences before and after compatibility.

Conclusion:
After the compatibility of frankincense and myrrh, the absorption of effective components was improved
to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating
the in vivo effect mechanism of frankincense and myrrh.
The Development of Stress Reactivity and Regulation in Children and
Adolescents
Authors: Filetti Clarissa , Kane-Grade Finola , Gunnar Megan 
Published: August 2023

Abstract:
Adversity experienced in early life can have detrimental effects on physical and mental
health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA)
axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspectives
that guide stress reactivity and regulation research, the anatomy and physiology of the axis, developmental
changes in the axis and its regulation, brain systems regulating stress, the role of genetic
and epigenetics variation in axis development, sensitive periods in stress system calibration, the social
regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiology
and development. Understanding the development of stress reactivity and regulation is crucial for
uncovering how early adverse experiences influence mental and physical health.
Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the
Treatment of Major Depressive Disorder
Authors: Su Wen-Jun , Hu Ting , Jiang Chun-Lei 
Published: August 2023

Background:
Abundant evidence suggests that inflammatory cytokines contribute to the
symptoms of major depressive disorder (MDD) by altering neurotransmission, neuroplasticity, and neuroendocrine
processes. Given the unsatisfactory response and remission of monoaminergic antidepressants,
anti-inflammatory therapy is proposed as a feasible way to augment the antidepressant effect. Recently,
there have been emerging studies investigating the efficiency and efficacy of anti-inflammatory
agents in the treatment of MDD and depressive symptoms comorbid with somatic diseases.

Methods:
In this narrative review, prospective clinical trials focusing on anti-inflammatory treatment
for depression have been comprehensively searched and screened. Based on the included studies, we
summarize the rationale for the anti-inflammatory therapy of depression and discuss the utilities and
confusions regarding the anti-inflammatory strategy for MDD.

Results:
This review included over 45 eligible trials. For ease of discussion, we have grouped them into
six categories based on their mechanism of action, and added some other anti-inflammatory modalities,
including Chinese herbal medicine and non-drug therapy. Pooled results suggest that anti-inflammatory
therapy is effective in improving depressive symptoms, whether used as monotherapy or add-on therapy.
However, there remain confusions in the application of anti-inflammatory therapy for MDD.

Conclusion:
Based on current clinical evidence, anti-inflammatory therapy is a promisingly effective
treatment for depression. This study proposes a novel strategy for clinical diagnosis, disease classification,
personalized treatment, and prognostic prediction of depression. Inflammatory biomarkers are
recommended to be assessed at the first admission of MDD patients, and anti-inflammatory therapy
are recommended to be included in the clinical practice guidelines for diagnosis and treatment. Those
patients with high levels of baseline inflammation (e.g., CRP > 3 mg/L) may benefit from adjunctive
anti-inflammatory therapy.
Role of GLP-1 Receptor Agonist in Diabetic Cardio-renal Disorder:
Recent Updates of Clinical and Pre-clinical Evidence
Authors: Seksaria Sanket , Dutta Bhaskar Jyoti , Kaur Mandeep , Gupta Ghanshyam Das , Bodakhe Surendra H. , Singh Amrita 
Published: August 2023

Abstract:
Cardiovascular complications and renal disease is the growing cause of mortality in patients
with diabetes. The subversive complications of diabetes such as hyperglycemia, hyperlipidemia
and insulin resistance lead to an increase in the risk of myocardial infarction (MI),
stroke, heart failure (HF) as well as chronic kidney disease (CKD). Among the commercially
available anti-hyperglycemic agents, incretin-based medications appear to be safe and effective in
the treatment of type 2 diabetes mellitus (T2DM) and associated cardiovascular and renal disease.
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to be fruitful in reducing
HbA1c, blood glucose, lipid profile, and body weight in diabetic patients. Several preclinical and
clinical studies revealed the safety, efficacy, and preventive advantages of GLP-1RAs against diabetes-
induced cardiovascular and kidney disease. Data from cardio-renal outcome trials had highlighted
that GLP-1RAs protected people with established CKD from significant cardiovascular
disease, lowered the likelihood of hospitalization for heart failure (HHF), and lowered all-cause
mortality. They also had a positive effect on people with end-stage renal disease (ESRD) and
CKD. Beside clinical outcomes, GLP-1RAs reduced oxidative stress, inflammation, fibrosis, and
improved lipid profile pre-clinically in diabetic models of cardiomyopathy and nephropathy that
demonstrated the cardio-protective and reno-protective effect of GLP-1RAs. In this review, we
have focused on the recent clinical and preclinical outcomes of GLP-1RAs as cardio-protective and
reno-protective agents as GLP-1RAs medications have been demonstrated to be more effective in
treating T2DM and diabetes-induced cardiovascular and renal disease than currently available
treatments in clinics, without inducing hypoglycemia or weight gain.
Flavonoids from Kalanchoe ×laetivirens Impair Survival and Immunity of
Atta sexdens (Hymenoptera: Formicidae)
Authors: Silva Melo Márcio , Santos Silva Cynthia Lhourrana , Tenório Amanda Caroline  Teles , Silva Melo Bruno , da Silva Barbosa Rone , Sarmento Renato Almeida , Holzbach Juliana Cristina , Barbosa Cruz Állefe , Nascimento Isabele Rodrigues , de Souza Danival José 
Published: August 2023

Background:
The active secondary metabolites of various Kalanchoe species are promising for
controlling insects and other agricultural pests.

Objective:
This study aimed to evaluate the mortality and immune responses of the leafcutter ant Atta
sexdens (L.) after treatment with Kalanchoe ×laetivirens (Desc.) aqueous extract. The effects on an
aquatic organism used as a bioindicator, Chironomus xanthus (Rempel), were also evaluated.

Methods:
Different K. ×laetivirens concentrations were prepared by dilution in honey to assess the toxicity
and determine the median lethal concentration (LC50) for A. sexdens workers. The haemocytes of
workers treated with a sublethal concentration (0.005 g/mL) were counted.

Results:
The plant extracts induced high mortality in A. sexdens workers. All concentrations, except 0.001
g/mL, increased mortality rates. The sublethal concentration negatively affected the immune system of A.
sexdens workers 48 and 72 h after ingestion. The flavonoids 4″″-acetylsagittatin A, sagittatin A and the
nucleosides uridine and adenosine were identified. The LC50 of the K. ×laetivirens (128.1 mg /L) was
determined for the non-target organism, C. xanthus.

Conclusion:
These natural compounds can be used in future research to plan alternative control strategies
for leafcutter ants in forests and other agroecosystems.
Chemical Composition and Biological Activities of the Extracts of Peperomia
pellucida Fractions
Authors: Men Tran Thanh , Phien Huynh Hong , Son Nguyen Hoang , Thao Truong Thi Phuong , Nhu Nguyen Thi Bich , Uyen Nguyen Thi To , De Tran Quang , Khang Do Tan 
Published: August 2023

Background:
Peperomia pellucida is a medicinal and vegetable plant used worldwide, representing
a multi-purpose vegetable with applications in the pharmaceutical, food and cosmetic industries.

Objective:
This study evaluated the antioxidant, antibacterial, antifungal, anti-inflammatory, and antidiabetic
potential of fractional extracts from P. pellucida plant derived from Can Tho City, Vietnam.

Methods:
Four fractional extracts were prepared using different polarity solvents (hexane, dichloromethane,
ethyl acetate) and used to determine the best extract for each biological property. The fractions’
total alkaloid, phenolic, and flavonoid content were observed. The four extracts were evaluated for their
potential bioactivities: antioxidant, antibacterial, antifungal, anti-inflammatory, and antidiabetic.

Results:
Correspond with the hexane, dichloromethane, ethyl acetate, and aqueous fractions, the total
content of alkaloids was determined to be 255 ± 23.8; 157 ± 14.0; 219 ± 6.55; 221 ± 6.23 (mg AE/g extract),
the total phenolic content was 112 ± 3.34; 141 ± 1.77; 234 ± 29.5; 123 ± 5.04 (mg GAE/g extract),
whereas the total content of flavonoids was 84.49 ± 4.53; 33.77 ± 1.26; 367.8 ± 3.37; 34.49 ± 4.53 (mg
QE/g extract), respectively. The ethyl acetate fraction gave the best efficiency in DPPH, ABTS, iron reduction,
and TAC methods (IC50 = 334 ± 2.10 μg/mL; 51.4 ± 0.41 μg/mL; 79.1 ± 0.40 μg/mL; and 83.0 ±
0.17 μg/mL, respectively). Antibacterial activity was investigated on 5 strains of Bacillus cereus, Escherichia
coli, Staphylococcus aureus, Salmonella typhimunum, Pseudomonas aeruginosa; the results
showed that the extracts were resistant to 5 strains of bacteria, especially best resistant in 2 fractions of
ethyl acetate and aqueous. The minimum inhibitory concentration (MIC) value ranged from 0.5 to 32
mg/mL, while the minimum bactericidal concentration (MBC) value ranged from 16 to 64 mg/mL. The
best anti-inflammatory activity was ethyl acetate with an IC50 value of 216.7 ± 7.2 μg/mL, close to that of
Diclofenac at 205.4 ± 0.5. The antidiabetic activity was investigated based on the ability to inhibit α-
amylase and α-glucosidase enzymes. The results showed that the best α-amylase inhibitors were hexane
and dichloromethane (IC50 = 208.83 ± 2.41 and 191.60 ± 1.27 μg/mL, respectively), roughly equal to the
acarbose (155.68 ± 2.59 μg/mL). The best α-glucosidase inhibitory fraction was ethyl acetate (IC50 of
157.04 ± 0.23 μg/mL), close to that of acarbose (116.45 ± 0.21 μg/mL).

Conclusion:
Fractional extracts from P. pellucida distributed in gardens of Can Tho City, Vietnam, contain
potential antioxidant, antibacterial, antifungal, anti-inflammatory, and antidiabetic bioactive compounds.
A Robust Adaptive Control Strategy for Electro-hydraulic Servo Based on
Friction Compensation
Authors: Yue Luyou , Wang Zhiqing , Huang Hua , Rao Junsen , Zhu Xunyi , Zhang Xinxing , Zhang Bing 
Published: August 2023

Background:
The electro-hydraulic servo system has the advantages of high stiffness, fast response speed, high precision and power-to-weight ratio.

Objective:
In this patent, an adaptive robust control strategy based on friction compensation is proposed for insufficient control accuracy due to a large number of nonlinearities and uncertainties in the system.

Methods:
In this patent, the mathematical relationship between the physical quantities of the valve-controlled cylinder is analyzed. Then the mathematical model of valve controlled cylinder considering the main nonlinearity and uncertainty of the system is established. The fuzzy proportion-integral-derivative, deterministic robust, and adaptive robust single-cylinder trajectory tracking controllers are designed and the tracking performance of different reference trajectories is analyzed by MATLAB/Simulink software.

Results:
In this patent, all the three controllers can track the reference trajectories smoothly. Adaptive robust control strategy can make the uncertain parameters of system converge and approach truth value.

Conclusion:
In this patent, the adaptive robust control strategy has the function of online parameter adjustment. When tracking accuracy is taken as the index, its tracking effect is better than fuzzy proportion-integral-derivative and deterministic robust.
Chromene as Antioxidants
Authors: Kamal Kant Arya Rajeshwar , Kumar Arun , Guglani Anchala , Bisht Dheeraj , Kumar Deepak 
Published: August 2023

Chromene is a heterocyclic compound that contains oxygen in its ring. It is
widely obtained naturally from both animals and plants, and it is an integral part of
alkaloids, tocopherol, anthocyanins, and flavonoids. The 2-oxo-2H-chromene is called
coumarins, and coumarins have excellent antioxidant potential due to the presence of
the phenol group, more than 1300 coumarins have been identified to date. The
chromene scaffold in coumarins has the structural modification ability that makes it the
structure of choice for medicinal purposes. Various medicines can be synthesized by
using a chromene scaffold e.g. asthma, hypertension, antifungal, and antimicrobial.
Chromene shows a good antioxidant potential that depends on its hydrogen ion releasing capacity and stabilizes hydrogen with the help of a high resonating structure.
The bond length between bonds also enhances the free radical scavenging function. In
this chapter, we have discussed some chromene derivatives and their antioxidant
potential, and the effect of cyclic structure on the antioxidant’s function.