bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Metabolic Pathways and Products of Ten Aconitum Alkaloids in Sanwujiao Pills
from Eight Organs of Mice by UHPLC-Q-TOF-MS/MS
Authors: Pei Wen-Han , Huang Yu-Feng , Xie Ying , Qu Yuan , He Fan , Zhou Hua 
Published: May 2023

Background:
Sanwujiao pill (SWJP) is a Chinese herbal preparation widely used in China. It is an essential
medicine for treating rheumatism and blood stasis. However, its safety in clinical use has always been the focus
of patients because it contains toxic herbs of Aconitum carmichaelii Debx. and A. vilmorinianum Kom.

Objective:
To further reveal the pharmaceutical and toxic effect substances and the action mechanism of SWJPs, the
metabolites and their pathways of ten Aconitum alkaloids (AAs) in the preparation at different time points after oral
administration in eight organs of mice were investigated.

Method:
The biosamples were investigated by a four-step strategy of UPLC-Q-TOF-MS /MS technology.

Results:
Aconitine (AC), mesaconitine (MA), and hypaconitine (HA) were not detected in any organs. The highest
concentrations of the other seven AAs occurred at 0.5 h. Yunaconitine (YAC) was not detected in the brain; all seven
AAs had the lowest concentration in the brain, and the metabolism was slow in the stomach. Twelve predicted metabolites
were identified, the kidney and stomach were their primary distribution locations, and the most metabolites
were found at 0.5h. The main metabolic pathways of the ten AAs were demethylation, deethylation, deoxygenation,
hydroxylation, and deacetylation.

Conclusion:
This is the first report about the metabolism of ten AAs in SWJPs in mice. Significantly, the metabolic
pathways and products of four hidden toxic AAs were analyzed in vivo for the first time. The results were of great
significance for the safety and effectiveness of SWJPs in clinical application.
Cholinergic Transporters Serve as Potential Targets in Alzheimer’s
Disease
Authors: Bist Renu , Bhatt D.K. 
Published: May 2023

Abstract:
Alzheimer's disease (AD) is a specific brain disease that gradually worsens
due to dementia over a long period. AD accounts for almost 60% to 80% of cases of
dementia. Any damage to neurons affects their ability to communicate, leading to
alteration in thinking, behaviour and feelings. Besides mental, motor abilities of an
individual may also be affected due to AD. Therefore, it is cardinal to understand the key
mechanisms by which either AD progression can be ceased or, after the onset of the
disease it could be reverted. Both of these steps need the identification of a particular
receptor or a molecular marker through which a drug can enter the neurons. Cholinergic
transporters are such potential targets of AD, which regulate the movement of
acetylcholine and thus regulate the nerve impulse conduction in the brain. The current
article entails information regarding a variety of cholinergic transporters, which will
provide a research gap to the global scientific community.
AmpC Inhibition: An Explicit Approach against Multi-Drug Resistance (MDR)
Authors: Kaushik Manish , Kaushik Aditi , Jain Akash , Chaudhary Jasmine , Gupta Vrinda 
Published: May 2023

Abstract:Multi-drug resistance and its transmission is a ubiquitous health issue worldwide. The beta-lactamase AmpC resistance is a major concern among all health settings like hospitals and child care centers, etc. The clinical pipeline of the new antibiotics remains dry due to the production of AmpC beta-lactamases by the bacteria to develop resistance against antibiotics. According to the global antimicrobial resistance and use surveillance system, the rate of resistance to ciprofloxacin an antibiotic commonly used to treat urinary tract infections, varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiellapneumoniae in different countries. The lack of comprehensiveness within the data makes a choice problematic for the selection of appropriate β- lactam antibiotic for the treatment of resistant microorganisms. Most experts agree it is prudent to avoid expanded-spectrum (i.e. third-generation) cephalosporins for the treatment of organisms posing the greatest risk of AmpC induction. Nonetheless, the development of specific inhibitors for the AmpC enzyme, either naturally or synthetically, is only unfolding. To date, there is no single and clinically active drug available that inhibits the AmpC enzyme and combats multidrug resistance and its transmission in individuals. The deficit of the enzyme inhibitor focused the researchers to work in the area. This present review will emphasize on the chemistry, and structure of clinically important and potent inhibitors against AmpC enzymes.
A Review of the Therapeutic Importance of Indole Scaffold in Drug
Discovery
Authors: Teraiya Nishith , Agrawal Khushbu , Patel Tarun M. , Patel Archita , Patel Samir , Shah Umang , Shah Shaileshkumar , Rathod Khushman , Patel Krupa 
Published: May 2023

Abstract:
Indole is known as a versatile heterocyclic building block for its multiple pharmacological activities and has a high probability of success in the race for drug candidates. Many natural products, alkaloids, and bioactive heterocycles contain indole as the active principle pharmacophore. These encourage the researchers to explore it as a lead in the drug development process. The current manuscript will serve as a torchbearer for understanding the structurally diverse class of indole derivatives with extensive pharmacological activity. The current manuscript describes the intermediates and their functional groups responsible for superior biological activity compared to the standard. The review is written to help researchers to choose leads against their target but also to provide crucial insight into the design of a hybrid pharmacophore-based approach in drug design with enhanced potential. The present reviews on the indole derivatives correlate the structures with biological activities as well as essential pharmacophores, which were highlighted. The discussion was explored under challenging targets like dengue, chikungunya (anti-viral), antihypertensive, diuretic, immunomodulator, CNS stimulant, antihyperlipidemic, antiarrhythmic, anti-Alzheimer’s, and neuroprotective, along with anticancer, antitubercular, antimicrobial, anti-HIV, antimalarial, anti-inflammatory, antileishmanial, anti-anthelmintic, and enzyme inhibitors. So, this review includes a discussion of 19 different pharmacological targets for indole derivatives that could be utilized to derive extensive information needed for ligand-based drug design. The article will guide the researchers in the selection, design of lead and pharmacophore, and ligand-based drug design using indole moiety.
The Role of Vitamin D in Carpal Tunnel Syndrome Risk and Supplementation Outcomes: A Systematic Review
Authors: Asgari Savadjani Shahin , Sherwin Catherine MT , Heidari-Soureshjani Saeid , Darvishi Mohammad , Mohammadian Amiri Mehdi 
Published: May 2023

Background:Carpal tunnel syndrome (CTS) is a debilitating neuropathy that accompa-nies pain and other physical limitations and disrupts the normal functioning of the victims' lives.Objective:We aimed to investigate Vitamin D's preventive and therapeutic effects on the occur-rence and remission of CTS symptoms.Methods:In this systematic review the PRISMA statement has been designed primarily. An exten-sive search was undertaken in various databases, including PubMed, Cochrane library, Web of Sci-ence, EMBASE, and Scopus. After considering the inclusion and exclusion criteria of the study, fi-nally, 19 articles were retrieved. The raw data were extracted and entered into an Excel form, and the study outcomes were investigated.Results:The main symptoms and tests, including functional score, nerve conduction, and pain, were improved after Vitamin D supplementation in CTS patients. However, they revealed worse scores in people with low Vitamin D levels. In addition, the scores of mentioned indices were worsened in people with lower serum Vitamin D levels. Nevertheless, some studies did not find a significant re-lationship between low serum 25(OH)D and more significant pain scores in CTS patients. In addi-tion, Vitamin D inserts its effects on CTS by regulating cell proliferation, nerve growth factor, sup-pression of oxidative stress and inflammatory cytokines, and improvement in cartilage and micro-vascular damage.Conclusion:Vitamin D supplementation can improve the symptoms in CTS patients, and low se-rum 25(OH)D can aggravate the symptoms of the disease and could be a risk factor for its occur-rence. However, more observational studies and clinical trials are needed.
Mixed Endometrioid Clear Cell Carcinoma of the Ovary: A Case Report
Authors: Hasanzadeh Malihe , Esmaeilpour Maryam , Mohammadi Mahdieh 
Published: May 2023

Background:
Despite the high percentage of pure forms of epithelial ovarian cancers
(EOC), mixed epithelial cancer of the ovary is extremely rare and accounts for less than 1% percent of
all epithelial ovarian cancers. Because of the low prevalence; there are only a few cases of mixed epithelial
cancers published in the literature. This study presents the case of a mixed endometrioid
(EC)/clear cell carcinoma (CCC), diagnosed in a woman with a complaint of low back pain and a history
of infertility.

Case Report:
We report the case of a 35-year-old woman who came to our clinic complaining of progressive
back pain and a history of infertility. Imaging showed a left ovarian mass that was compatible
with malignant tumors. The patient underwent open surgery and a frozen section evaluation of the tumor
was done during the operation. The pathology result demonstrated mixed CCC/EC histology in
the left ovary. We decided to perform a total abdominal hysterectomy as well as right salpingooophorectomy,
omentectomy, bilateral pelvic lymphadenectomy, and para-aortic lymphadenectomy.
Adjuvant chemotherapy was administrated postoperatively.

Conclusion:
Although epithelial cancers account for more than 90% of all ovarian cancers (OC), developing
mixed forms of epithelial cancers is extremely rare, and there are little data available in the
literature about their presentation and histopathological features. The main purpose of this article was
to report a mixed CCC/EC and to discuss different aspects of this rare histologic type of OC. More research
is needed to determine metastatic potential as well as the likelihood of recurrence of these
unique neoplasms.
Enrichment of Isaria felina Culture with Selenium Enhances its in vivo Antitumor
Effects on H22 Hepatoma via Decreasing the Expression of VEGF
Authors: Yang Xihua , Yang Yongming , Zhao Lili , Chen Lixia , Wang Jing , Yan Lei , Ma Jinfeng 
Published: May 2023

Background:
The polysaccharide extract of C. sinensis, Isaria felina (IF), has antitumor effects. Selenium
(Se) can improve disease prevention and reduce the toxicity of toxic elements, but the effect of Se-enriched IF on hepatoma
remains unknown.

Objective:
To determine the organic transformation of Se and compare the antitumor effects between Se-enriched IF
(IF-Se) and IF on xenograft H22 hepatoma-bearing mice.

Methods:
Se was added to the solid-state culture medium, and the organic Se content was detected by HPLC-ICP-MS.
Forty-two Kunming mice were randomly divided into seven groups to test the antitumor effects of low- (300 mg/kg)
and high- (600 mg/kg) doses of IF-Se and IF through xenograft. Huai’er granules were administered as the positive
control. In addition, interleukin (IL)-2 and vascular endothelial growth factor (VEGF) expressions were measured by
enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method.

Results:
The conversion rate in the IF-Se70, IF-Se140, and IF-Se280 groups were 91.5%, 93.4%, and 89.3%, respectively.
Therefore, IF-Se140 was used to carry out the subsequent experiments. The tumor inhibition rates of IF-Se were
significantly higher compared with IF (P < 0.05). Moreover, the spleen coefficient, IL-2, and VEGF expression levels
significantly decreased (all Ps < 0.05), and the thymus coefficient significantly increased (P < 0.05) in the high-dose
IF-Se group compared with the model control group.

Conclusion:
The inhibitory effects of IF on H22 hepatoma-bearing mice were enhanced after Se enrichment. Therefore,
Se-enriched IF might be a new strategy for treating hepatoma.
Nano Drug Delivery Systems: A Mini-review
Authors: Syam Kumar Valli Nachiyar , Sunkar Swetha , Selvaraj Karthick Raja Namasivayam , Nellore Jayshree 
Published: May 2023

Abstract:
Medical nanotechnology is surfacing as a challenging arena covering new biomedical applications,
such as drug delivery, treatment, nano diagnosis, controlled drug release, regenerative medicine,
and disease prevention. The recent developments in the field of Nanotechnology have enabled the
nanostructures to overcome the problems associated with drug delivery making them the promising
agents for site-specific drug delivery with reduced side effects and the best treatment outcome. These
nanodrug delivery systems are designed in such a way that they can breach the biological barrier and deliver
the drug in a site-specific manner. They enhance the effectiveness of drugs by increasing the stability
and water solubility of drugs and by increasing the rate at which these nano drug complexes are taken
up by the cells and tissues. Dendrimers, nanocrystals, nano-polymer NPs, and liposomes are futuristic
nano-based drug delivery systems. Smart polymers are future drug-delivery systems with cutting-edge
precise technology that are employed in effective cellular targeting based on temperature, pH, photoresponsive,
conductive and magnetic responsive smart polymers. This review provides a comprehensive
view of various nanostructures and their application in drug delivery.
Aluminum Nano Stars with Localized Surface Plasmon Resonance and
Field Enhancement
Authors: Sharma Chhaya , Katyal Jyoti , Singh Rina 
Published: May 2023

Aim:
The Finite Difference Time Domain approach has been used to assess the localised surface
plasmon resonance and field enhancement for Al nanostars. The structure's potential as a refractive
index sensor has been demonstrated.

Background:
Research on plasmonics has been possible in a variety of domains, including sensors,
SERS, solar cells, and others, due to a tenability in the plasmon wavelength caused by a simple change in
shape, size, or external environment. The growth of plasmonics has been greatly aided by the creation of
novel ways for creating metallic nanostructures and a large deal of work on the creation of numerical algorithms
to cope with arbitrarily shaped metallic nanostructures. The LSPR and field enhancement of an Al
nano-star were the main topics of this paper. A larger RIS factor is obtained after adjusting the refractive
index sensitivity parameter, making it appropriate for refractive index-based sensor nanostructures.

Objective:
This study's primary goal is to provide a comparative analysis of the refractive index sensitivity
factor for Al nanostars dependent on their size and number of arms.

Methods:
Al nano star's LSPR and field enhancement have been assessed using the Finite Difference
Time Domain (FDTD).

Results:
By altering the size and number of arms of the nano star, the tenability of the plasmonic peak has
been assessed, and it has been found that the peak is sensitive to the ambient dielectric constant. A study has
been done on the refractive index sensitivity parameter. A higher sensitivity of about 370 nm/RIU, which
is significantly higher than that of other metallic Nanostar (NS), is seen after adjusting the size and number of
arms. A wide range of applications is covered by the Al NS field enhancement pattern, which exhibits
stronger enhancement with no aggregation at the plasmon peak.

Conclusion:
For LSPR sensing applications, the impact of modifying the environmental dielectric constant
is examined. By changing the size and quantity of the Al NS's arms, we were able to compare the
refractive index sensitivity parameter. The bigger size NS exhibits more peaks due to the contribution of
the multipole; however, after tuning a number of parameters, better sensitivity in comparison to Au and
Ag nanostar has been attained. Al NS can therefore be a promising sensing material for refractive index
sensing employing LSPR properties.
Multi-Objective Optimization in the Presence of OGIPFC Using NSMMP Algorithm
Authors: Mallala Balasubbareddy , Papana Venkata Prasad , Palle Kowstubha 
Published: May 2023

Background:
Customers expect quality, uninterrupted power with cost-effective electricity
in the latest trend. However, outages, severe storms, old infrastructure, and cost pressures can
lead to ambiguity in power generation and transmission. To improve line power transmission capability,
the right flexible AC transmission systems (FACTS) device may save millions of dollars.

Methods:
In this study, a FACTS controller named Optimal Generalized Interline Power Flow Controller
(OGIPFC) was developed. Furthermore, for optimization, the Modified Marine Predator Algorithm
(MMPA), which is a modification of the recently developed Marine Predator Algorithm
(MPA). The optimum technique was used to evaluate a set of prioritized considered objective minimizations.
A variety of factors must be maximized, such as generation cost, emissions, and power
loss.

Results:
The performance of the proposed algorithm was analysed on benchmark test functions, and
then single objective optimization problems of standard IEEE-30 bus system were solved and compared
with the existing algorithms. The proposed algorithm was restricted to solving the single objective
problem only, so it was further implemented with non-dominating sorting to solve the multiobjective
optimization problem. The proposed multi-objective version is named as Non-dominating
Sorting Modified Marine Predator Algorithm (NSMMPA), and it was validated on benchmark test
functions and the IEEE-30 bus system.

Conclusion:
Finally, the OPF problem was solved with the incorporation of OGIPFC using the proposed
methods, which resulted in better solutions and made the system more effective in operation.
Automated System for Movie Review Classification using BERT
Authors: Rana Shivani , Kanji Rakesh , Jain Shruti 
Published: May 2023

Aims:Text classification emerged as an important approach to advancing Natural Language Processing (NLP) applications concerning the available text on the web. To analyze the text, many applications are proposed in the literature.Background:The NLP, with the help of deep learning, has achieved great success in automatically sorting text data in predefined classes, but this process is expensive and time-consuming.Objectives:To overcome this problem, in this paper, various Machine Learning techniques are studied & implemented to generate an automated system for movie review classification.Methodology:The proposed methodology uses the Bidirectional Encoder Representations of the Transformer (BERT) model for data preparation and predictions using various machine learning algorithms like XG boost, support vector machine, logistic regression, naïve Bayes, and neural network. The algorithms are analyzed based on various performance metrics like accuracy, precision, recall and F1 score.Result:The results reveal that the 2-hidden layer neural network outperforms the other models by achieving more than 0.90 F1 score in the first 15 epochs and 0.99 in just 40 epochs on the IMDB dataset, thus reducing the time to a great extent.Conclusion:100% accuracy is attained using a neural network, resulting in a 15% accuracy improvement and 14.6% F1 score improvement over logistic regression.
mHealth for the Self-management of Knee Osteoarthritis: Scoping Review
Authors: Kitagawa Takashi , Hayashi Masateru 
Published: May 2023

Background
Educating patients on the self-management of knee osteoarthritis (OA) reportedly reduces pain, improves activities of daily living, and even reduces health care costs.

Objective
This scoping review will summarize the current evidence on mobile health (mHealth) and smartphone app–based disease self-management for patients with knee OA.

Methods
PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL were systematically searched in May 2021 using the keywords “knee osteoarthritis,” “mobile health,” and “self-management.” Studies that investigated patients with knee OA based on radiography or clinical diagnosis were included. The following criteria were applied to the mobile phone apps included in the search-derived studies: the ability to (1) record and manage symptoms, (2) provide patient education, and (3) guide and record activities of daily living. Studies eligible for inclusion in this scoping review were interventional trials or observational studies published in English.

Results
This scoping review included 8 reports, of which 3 were randomized controlled trials and 1 was a conference abstract. Most studies provided data on the outcomes of pain, physical function, and quality of life.

Conclusions
An increasing number of reports are addressing the effectiveness of mHealth in patients with knee OA, and the data suggest that mHealth efficacy is similar to conventional management of health.

International Registered Report Identifier (IRRID)
RR2-10.17504/protocols.io.buuxnwxn
Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study
Authors: Plachta-Danielzik Sandra , Grasskemper Lena , Schmidt Karen , Schreiber Stefan , Bokemeyer Bernd 
Published: May 2023

Background
Filgotinib was approved in Germany for treating patients with moderate to severe active ulcerative colitis in November 2021. It represents a preferential Janus kinase 1 inhibitor. The FilgoColitis study began recruiting immediately after approval and aims to assess filgotinib effectiveness under real-world conditions with a particular focus on patient-reported outcomes (PROs). The novelty of the study design is the optional inclusion of 2 innovative wearables, which could provide a new layer of patient-derived data.

Objective
The study investigates quality of life (QoL) and psychosocial well-being of patients with active ulcerative colitis during long-term exposure to filgotinib. PROs related to QoL and psychometric profiles (fatigue and depression) are collected alongside with disease activity symptom scores. We aim to evaluate physical activity patterns collected by wearables as an addition to traditional PROs, patient-reported health status, and QoL in different phases of disease activity.

Methods
This is a prospective, single-arm, multicentric, noninterventional, observational study with a sample size of 250 patients. QoL is assessed with validated questionnaires: the Short Inflammatory Bowel Disease Questionnaire (sIBDQ) for the disease-specific QoL, the EQ-5D for the general QoL, and the fatigue questionnaire (Inflammatory Bowel Disease-Fatigue [IBD-F]). Physical activity data are collected from patients using wearables (SENS motion leg sensor [accelerometry] and smartwatch, GARMIN vívosmart 4).

Results
The enrollment started in December 2021 and was still open at the date of submission. After 6 months of study initiation, 69 patients were enrolled. The study is expected to be completed in June 2026.

Conclusions
Real-world data for novel drugs are important to assess effectiveness outside of highly selected populations represented by randomized controlled trials. We examine whether patients’ QoL and other PROs can be supplemented with physical activity patterns measured objectively. Use of wearables with newly defined outcomes represents an additional observational tool for monitoring disease activity in patients with inflammatory bowel disease.

Trial Registration
German Clinical Trials Register DRKS00027327; https://drks.de/search/en/trial/DRKS00027327

International Registered Report Identifier (IRRID)
DERR1-10.2196/42574