bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of Multitarget Inhibitors as Tracheal Smooth Muscle Relaxants
Authors: Bhatia Neela M. , Bhatia Manish S. , Mohanty Sibaprasad K. , Parulekar Rishikesh S. , Joshi Amruta V. , Ashtekar Snehal S. 
Published: February 2023

Introduction:
Asthma complications and adverse effects associated with steroidal therapy
highlight the need for non-steroidal compounds intercepting asthmatic pathophysiology at multiple
targets. The present investigation was carried out to evaluate the tracheal smooth muscle relaxant effect
of virtually designed, combinatorially synthesized polyfunctional N-heteroarylamides.

Methods:
Virtual screening and molecular docking studies of designed compounds were performed
using PyRx and AUTODOCK 4.2 software against molecular targets viz. FLAP, LTB4, and H1 receptor.
Cross-validation of virtual screening results and active site, confirmation was performedusingVlife
MDS software version 3.5. The combinatorial approach was used to synthesize designed compounds in
which heterocyclic amines were reacted with substituted aromatic acid chlorides by nucleophilic substitution
reaction to obtain a 5x5 mini-library. The structures of synthesized leads were confirmed by
infrared and proton magnetic resonance spectroscopic analysis. Synthesized compounds were evaluated
for their smooth muscle relaxation effect on isolated goat tracheal smooth muscle.

Results:
Results were calculated as a percent decrease in contraction response observed using histamine
and LTB4. The tested compounds produced anticipated tracheal smooth muscle relaxant activity.
Based on the results of screening the structure-activity relationships (SAR) have been reported.

Conclusion:
Present study concluded that synthesized polyfunctional N-heteroarylamides have a tracheal
smooth muscle relaxant effect. The mode of action is predicted from the analysis of virtual
screening results. A good correlation was observed between virtual screenings and biological activities
of lead molecules suggesting the rationale used to optimize the structural requirements of a ligand for
selected targets is appropriate.
Stem Cells and Tumor-Killing Virus to Target Brain Tumor: In Pursuit to
Bring a Potential Delivery Vehicle for the Central Nervous System Tumors
Authors: E. Vignesh Balaji , Ranganath Pai K. Sreedhara 
Published: February 2023

Abstract:
To target brain cancer, various therapeutic options are present to fight against cancer cells.
But the existing therapies are not showing a proper curation of cancer patients. Henceforth, activating
the immune cells and targeting oncogenes/proteins might be an emerging therapeutic approach to target
and destroy malignant brain tumor. Stem cells (SCs) are considered potential immunomodulators that
trigger the highly suppressed immune system in the tumor microenvironment. Also, engineered SCs can
repress the aberrantly expressed oncoproteins that cause tumor cell proliferation and growth. SCs have
an excellent migration capability to reach the infected site and support the regeneration of damaged
blood vessels and tissues. Likewise, oncolytic virotherapy (OVT) is a promising novel therapeutic molecule
in which genetically modified viruses can selectively replicate and destroy cancer cells without
harming healthy cells. Same as SCs, oncolytic viruses (OVs) tend to stimulate the host's innate and
adaptive immune response to battle against the advanced brain tumor. In clinical studies, various OVs
have shown good immunogenic responses with a high safety profile and tolerability against cancer patients
with reduced morbidity and mortality rate. SCs act as an attractive cargo for OVs which helps to
influence the tumor site and destroy the tumor volume. SCs protect the OVs from systemic degradation
and promote therapeutic efficacy against cancer cells. SCs carried OVs might be a potential therapeutic
way to bring an effective treatment option for brain tumors.
Nature-derived Alkaloids as a Promising Bioactive Compound in Drug Discovery to Meet Global Leishmania Needs
Authors: Sharifi Fatemeh , Mohamadi Neda , Abiri Ardavan , Sharifi Iraj , Harandi Majid Fasihi , Sharififar Fariba 
Published: February 2023

Background:Natural products have been important resources for potential drug development. Among the many classes of natural products, alkaloids have the most therapeutic applications. Treatment of leishmaniasis by chemical drugs remains a challenge because of toxic side effects, limited efficacy, and drug resistance. This review focuses to embrace all researches on leishmanicidal alkaloids over a specific range of time, with special consideration the molecular mechanism of action, and structure-related activity.Methods:All publications (in English) from Web of Science, PubMed, Science Direct, Scopus, and Google Scholar from 2000-2021 using a variety of keywords such as natural alkaloids, herbal alkaloids, marine alkaloids along with leishmaniasis were included in the present study. In this summary, the focus is mainly on natural alkaloids of plant, mineral, marine origin, etc., which have empirically demonstrated the antileishmanial effect.Results:Fourteen categories of alkaloids with anti-leishmaniasis activity were extracted from the articles. The highest number of alkaloids belonged to isoquinoline, indole, and quinoline alkaloids (21.78%, 20.67%, and 16.48% respectively). This review indicated that the mentioned alkaloids are able to inhibit the proliferation of parasites, the respiratory chain and protein synthesis, arrest the cell cycle, disrupt the mitochondrial membrane integrity, inhibit leishmanial topoisomerase, induce mitochondrial dysfunction, and changes in the parasite morphology.Discussion:The present study highlighted antileishmanial alkaloids that are active against different species of Leishmania in vitro and some of them are also active in visceral and cutaneous leishmaniasis models. However, more clinical studies are needed to clarify the anti-leishmanial activity of alkaloids against leishmania in detail.Conclusion:Among the reported compounds, two main classes of alkaloids including isoquinoline and indole alkaloids cover a wider range of anti-parasitic compounds, and structure-activity relationships (SAR) studies of these molecular skeletons may be good lead compounds and afford the structural clues to develop novel medicines with more selective therapeutic profiles.
Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review
Authors: Sharma Ravikant , Suravarjhula Lalitha , Banerjee Madhuparna , Kumar Gautam , Kumar Nitesh 
Published: February 2023

Abstract:
Targeted cancer therapy acts on targeted molecules, is less toxic to normal cells, and
acts more specifically on cancer cells. The two primary strategies for preventing malignancy
growth are the blocking of T-cell repression signals or forwarding of T-cell to tumor target with
both T and tumor-specific antibodies. The CAR comprises three domains, the extracellular antigen
recognition domain and the intracellular T-cell signaling domain, which participate in activating
T-cells. The two most common adverse effects of CAR T-cell treatment are cytokine release syndrome
(CRS) and cell-associated neurotoxicity syndrome (CANS). The adaptability of intracellular
signaling domains inside CARs allows the cell to counterbalance the downregulation of costimulatory
molecules produced by tumor cells, either indirectly or directly. The major disadvantage
of CAR-T cell therapy is off-target toxicity. Treatment with CARs expressing CD3,
CD123, Lewis Y, CLL-1, CD44v6, FLT3, and folate receptors showed promising results in preclinical
models of acute myeloid leukemia (AML). A recent study has revealed that B7-H3 CART
cells exhibit significant anticancer efficacy in a variety of solid tumor preclinical models, including
PDAC, ovarian cancer, neuroblastoma, and various pediatric malignancies. The notion of
SUPRA CAR, with its unique capacity to alter targets without the need to re-engineer, is a recent
innovation in CAR. Given the importance of NK cells in tumor development and metastatic defence,
NK cell-based immunotherapies, including adoptive transfer of NK cells, have garnered a
lot of interest. With the advancement of improved cellular manufacturing methods, novel cellular
engineering strategies, precision genome editing technologies, and combination therapy approaches,
we firmly believe that CAR-T cells will soon become an off-the-shelf, cost-effective, and potentially
curative therapy for oncogenesis.
Ursolic Acid: Historical Aspects to Promising Pharmacological Actions for
the Treatment of Central Nervous System Diseases
Authors: Singh Aditya , Ansari Vaseem A. , Mahmood Tarique , Ahsan Farogh , Wasim Rufaida 
Published: February 2023

Abstract:
Ursolic acid (UA) has been utilized to improve memory-related cognitive processes and
intellectual functions. This study aims to examine the ethnobotanical uses, phytochemical composition,
toxicity, and central nervous system activities of UA. It promotes learning and memory and
has biological effects against Alzheimer's disease, Parkinson's disease, and cognitive impairment,
according to pharmacological investigations. UA did not cause any death, abnormal body weight,
or pathological diseases at any of the test doses. Furthermore, no behavioral, neurotoxin, coagulation,
haematological, or clinical chemistry changes were seen as a result of UA treatment. UA is
also used as a cosmeceutical product to improve skin functions. This article examines all
knowledge that has become available at this time for revealing the chemistry of the current has
been extensively investigated based on the data, resulting in UA derivatives with improved potency,
bioavailability, and stability being used to treat a number of non-communicable diseases. The
pharmacological activity of UA has been exploited to improve learning and memory and treat depression,
emotional stress, fatigue, anxiety, insomnia, Alzheimer’s disease, Parkinson’s disease,
epilepsy, and schizophrenia. The effects of UA on the central nervous system detailed in this review.
The majority of UA studies have been preclinical evaluations of cellular mechanisms in the
central nervous system, and more translational clinical research is needed to assess the drug's safety
and efficacy, as well as its favorable, biodistribution, which could be targeted using different
pathways and administration routes. Several in vitro and in vivo studies have investigated the
pharmacological properties of UA reporting neuroprotective effects and improvements in cognitive
function. These effects are attributed to its antioxidant, antiapoptotic, and anti-inflammatory
actions.
A Perspective into “TEL”-Tenofovir, Emtricitabine and Lamivudine
Antileprotic Activities by Drug Repurposing and Exploring
the Possibility of Combination Chemotherapy with Drug Rescued
Molecules for a Leprosy Free Mankind
Authors: Thangaraju Pugazhenthan , Yella Sree Sudha Tanguturi , Ramamurthy Vijayakumar Arumugam , Navabshan Irfan , Mohamed Thameemul Ansari Lappathai Habeeb 
Published: February 2023

Background:
Since leprosy bacilli cannot grow in vitro, testing for
antimicrobial resistance against Mycobacterium leprae or assessing the anti-leprosy
activity of new drugs remains hard. Furthermore, developing a new leprosy drug through
the traditional drug development process is not economically captivating for
pharmaceutical companies. As a result, repurposing existing drugs/approved medications
or their derivatives to test their anti-leprotic potency is a promising alternative. It is an
accelerated method to uncover different medicinal and therapeutic properties in approved
drug molecules.

Aims:
The study aims to explore the binding potential of anti-viral drugs such as
Tenofovir, Emtricitabine, and Lamivudine (TEL) against Mycobacterium leprae using
molecular docking.

Methods:
The current study evaluated and confirmed the possibility of repurposing antiviral
drugs such as TEL (Tenofovir, Emtricitabine, and Lamivudine) by transferring the
graphical window of the BIOVIA DS2017 with the Crystal Structure of a
phosphoglycerate mutase gpm1 from Mycobacterium leprae (PDB ID: 4EO9). Utilizing
the smart minimizer algorithm, the protein's energy was reduced in order to achieve a
stable local minima conformation.

Results:
The protein and molecule energy minimization protocol generated stable configuration
energy molecules. The protein 4EO9 energy was reduced from 14264.5
kcal/mol to -17588.1 kcal/mol.

Conclusion:
The CHARMm algorithm-based CDOCKER run docked all three molecules
(TEL) inside the 4EO9 protein binding pocket (Mycobacterium leprae). The interaction
analysis revealed that tenofovir had a better binding molecule with a score of -
37.7297 kcal/mol than the other molecules.
EFFECT OF ATTENDANCE ON THE ACADEMIC ACHIEVEMENT OF GIRLS AND BOYS IN SELECTED SCHOOLS OF CHANDIGARH
Authors: Mann Manpreet . , Zarabi Dazy . 
Published: February 2023

Schools play an important role in development of children and regular attendance in school helps in academic achievement, well being, self-esteem of children. This research studied 242 students for their academic achievement and their attendance in school. The results show that attendance in school is positively correlated with academic achievement. Key words: School attendance, academic achievement, School going adolescents.	Schools play an important role in overall development of children and adolescents. Schools have been sites for resilience oriented programming because of the easy access they provide to youth and are the link between academic success, school engagement and other child development goals like well-being, self-esteem and self-efficacy (Ungar et al 2004).	Research shows that attendance in school is an important factor in student achievement. Attendance in classrooms and in schools ensures continuity in the students learning process. When a student is absent from class whether unexcused or excused, it has an adverse effect on their academic performance and academic achievement. To understand the correlation between academic achievement and attendance, a study was carried out on school-enrolled adolescent girls and boys in schools across Chandigarh.
Predicting Patient Mortality for Earlier Palliative Care Identification in Medicare Advantage Plans: Features of a Machine Learning Model
Authors: Bowers Anne , Drake Chelsea , Makarkin Alexi E , Monzyk Robert , Maity Biswajit , Telle Andrew 
Published: February 2023

Background
Machine learning (ML) can offer greater precision and sensitivity in predicting Medicare patient end of life and potential need for palliative services compared to provider recommendations alone. However, earlier ML research on older community dwelling Medicare beneficiaries has provided insufficient exploration of key model feature impacts and the role of the social determinants of health.

Objective
This study describes the development of a binary classification ML model predicting 1-year mortality among Medicare Advantage plan members aged ≥65 years (N=318,774) and further examines the top features of the predictive model.

Methods
A light gradient-boosted trees model configuration was selected based on 5-fold cross-validation. The model was trained with 80% of cases (n=255,020) using randomized feature generation periods, with 20% (n=63,754) reserved as a holdout for validation. The final algorithm used 907 feature inputs extracted primarily from claims and administrative data capturing patient diagnoses, service utilization, demographics, and census tract–based social determinants index measures.

Results
The total sample had an actual mortality prevalence of 3.9% in the 2018 outcome period. The final model correctly predicted 44.2% of patient expirations among the top 1% of highest risk members (AUC=0.84; 95% CI 0.83-0.85) versus 24.0% predicted by the model iteration using only age, gender, and select high-risk utilization features (AUC=0.74; 95% CI 0.73-0.74). The most important algorithm features included patient demographics, diagnoses, pharmacy utilization, mean costs, and certain social determinants of health.

Conclusions
The final ML model better predicts Medicare Advantage member end of life using a variety of routinely collected data and supports earlier patient identification for palliative care.
The Effects of Online Self-management Interventions for Patients With Mood Disorders: Protocol for a Systematic Review and Meta-analysis
Authors: Ahn Junggeun , Kim Jiu 
Published: February 2023

Background
Self-management has become important as a complementary approach to the recovery of patients with mood disorders, and the need for a remote intervention program has been revealed in relation to the COVID-19 pandemic.

Objective
The aim of this review is to systematically review the studies for evidence on the effects of online self-management interventions based on cognitive behavioral therapy or psychoeducation for patients with mood disorders and to verify the statistical significance of the effectiveness of the interventions.

Methods
A comprehensive literature search will be conducted using a search strategy in nine electronic bibliographic databases and will include all randomized controlled trial studies conducted up through December 2021. In addition, unpublished dissertations will be reviewed to minimize publication bias and to include a wider range of research. All steps in selecting the final studies to be included in the review will be performed independently by two researchers, and any discrepancies will be resolved through discussion.

Results
Institutional review board approval was not required because this study was not conducted on people. Systematic literature searches, data extraction, narrative synthesis, meta-analysis, and final writing of the systematic review and meta-analysis are expected to be completed by 2023.

Conclusions
This systematic review will provide a rationale for the development of web-based or online self-management interventions for the recovery of patients with mood disorders and will be used as a clinically meaningful reference in terms of mental health management.

International Registered Report Identifier (IRRID)
DERR1-10.2196/45528
The Impact of COVID-19 Pandemic on Homestays and Optimism in Kepulauan Seribu on Tourism Future through Smart Tourism
Authors: Ismail Ervan , Sumardjo Sumardjo , P. Lubis Djuara , A. Kinseng Rilus 
Published: February 2023

Tourism stakeholders must seek out innovative tactics to survive and thrive in the face of adversity. Switching to digital media and developing new digital inventions is thought to be the best option (Heliany, 2019; Irwan & Novianti, 2021). Based on this, we consider it important to see the impact of the COVID-19 pandemic on Kepulauan Seribu tourism and its relation to digital communication as an effort to minimize the impact of the pandemic which aims to see the optimism of homestay owners. This article provides an overview of the COVID-19 pandemic impact on tourism business owners of homestays in Kepulauan Seribu until 2021Objectives: This article provides an overview of the COVID-19 pandemic impact on tourism business owners of homestays in Kepulauan Seribu until 2021. This study aims to measure the awareness level of health protocols and the decline in income for homestay owners. This study also aims to describe the future recovery opportunities through the readiness of digital communication towards smart-tourism in Kepulauan Seribu and the optimism of homestay owners in developing their homestays in the future.Methodology: This study uses a quantitative descriptive approach. The collection of questionnaire data uses cluster sampling starting on June 23, 2021 until October 7, 2021 with a total of 308 respondents based on collected questionnaires. The study was carried out on 9 islands during the COVID-19 pandemic and under the policy of Restrictions towards Community Activities (abbreviated to PPKM) by Indonesia’s government. The presentation of descriptive data analysis uses SPSS Version 24. To strengthen the analysis, in-depth interviews were carried out with key informants.Finding: The results of data analysis show a 60% decrease in homestay income and the number of tourists during the COVID-19 pandemic. The biggest use of digital marketing is for imaging activity, followed by digital transaction activity, marketing, and receiving criticism and suggestions as only less than 50% of homestay owners have attended training. Although affected by the COVID-19 pandemic, homestay owners are optimistic to continue to develop the capacity of their homestay in the future.Conclusion: The availability of infrastructure to support smart tourism is sufficient. The readiness of human resources in the form of skills in maximizing the use of digital communication for tourism still needs to be supported through continuous digital communication training programs and assistance by tourism-aware groups. Keywords: COVID-19 pandemic; digital communication; Kepulauan Seribu; smart-tourism
Do Overconfidence and Herding Affect Stock Investment Decision? Indonesian Cases During Pandemic Covid-19
Authors: Tamara Dewi 
Published: February 2023

Objective: To analyze the effect of overconfidence and herding on stock investment decision-making with risk perception as a mediating variable and financial literacy as a moderating variable.Methodology: The survey was launched and replied by 99 stock investors. The data is analyzed using Structural Equation Modeling with the software Smartpls 3.0.Findings: The results show that herding had a positive and significant effect on stock investment decisions. Overconfidence does not have either a direct or indirect effect on stock investment decisions. Risk perception also does not mediate overconfidence in stock investment decisions. The Herding variable has an effect on stock investment decisions. However, financial literacy does not moderate herding and stock investment decisions. This research contributes in several ways. Firstly, overconfidence is not proven to indirectly affect stock investment decisions through risk perception. In other words, risk perception does not have a mediation effect. Overconfidence also does not affect stock investment decisions directly. Secondly, herding affects stock investment decisions positively. Finally, financial literacy does not moderate herding and stock investment decisions.Conclusion: The result showed that there was a significant positive effect of herding on stock investment decisions. Risk perception does not mediate overconfidence and stock investment decisions. Financial literacy does not moderate herding and stock investment decisions. Overconfidence also does not have a relation to stock investment position. In this research, the stock investment decision is mostly influenced by herding.