bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Mycophenolic Adenine Bis{phosphonate)s as Potential
Immunosuppressants
Authors: Pankiewicz K. W. , Malinowski K. , Jayaram H.  N. , Lesiak­ Watanabe K. , Watanabe K. A. 
Published: April 2022

Abstracts:
Mycophenolic acid (MPA) is the most potent and specific inhibitor of inosine monophosphate dehydrogenase (IMPDH). This compound was reported to bind the NAD site of IMPDH and mimic the binding of nicotinamide moiety of nicotinamide adenine dinucleotide. We linked MPA derivatives with the adenine moiety of NAD through a methylenebis(phosphonate) bridge to form novel mycophenolic adenine dinucleotides (MADs) which resemble well the intact natural cofactor. The MAD analogues differ by the length of the side chain (linker) between the aromatic ring of mycophenolic derivative and the -phosphorus atom of the adenosine bis(phosphonate) moiety. Regardless of the linker size, MADs were found to be
potent inhibitors of human IMPDH type I and type II with Ki's = 0.25-0.52 f..LM, an order of
magnitude less potent than MPA itself (Ki = 0.01-0.04 f..LM). The growth of K562 cells was inhibited by MPA (IC50 = 0.3 f..LM) and the MAD analogues (IC50 = 0.1-1.5 f..LM) with a similar
potency. Accordingly, a suppression of alloantigen-induced proliferation of human lymphocytes by the MAD analogues at concentration of 10-20 f..LM was equally effective as that observed for MPA. In contrast to MPA, MAD analogues were found to be resistant to glucuronidation in vitro. Since therapeutic potential of MPA is limited by its undesirable glucuronidation, the glucuronidation-resistant MAD analogues may be superior immunosuppressants if they are not glucuronidated in vivo.
Recent Advances in the Enantioselective Synthesis of β-Amino Acids
Authors: Juaristi Eusebio , López-Ruiz Heraclio 
Published: April 2022

Abstract:
The introductory section of this review presents some of the currently most compelling β-amino acid targets, according to their structural types: (α and β-aryl substituted, olefinic and alkynyl, α,α- and α,β-disubstituted, 'cyclic and conformationally restricted, fluorine­ containing, and phosphonic analogous β-amino acids. The main section highlights some of the very new (1996-1998), promising methodology for the enantioselective synthesis of β-amino acids, with especial emphasis on catalytic and enzymatic processes, as well as methods based on "chiral pool", "self-regeneration of stereogenic centers", diastereoselective nucleophilic additions to prochiral double bonds, and enantioselective reactions in the presence of chiral additives.
The Zinc-dependent HDACs: Non-histone Substrates and Catalytic Deacylation Beyond Deacetylation
Authors: Zheng Weiping 
Published: April 2022

Abstract:
Protein lysine side chain N(epsilon)-acylation and -deacylation play an important regulatory role in both epigenetic and non-epigenetic processes via a structural and functional regulation of histone and non-histone proteins. The enzymes catalyzing deacylation were traditionally termed as the histone deacetylases (HDACs) since histone proteins were the first substrates identified and the deacetylation was the first type of deacylation identified. However, it has now been known that, besides the seven sirtuins (i.e. SIRT1-7, the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent class III HDACs), several of the other eleven members of the mammalian HDAC family (i.e. HDAC1-11, the zinc-dependent classes I, II, and IV HDACs) have been found to also accept nonhistone proteins as native substrates and to also catalyze the removal of the acyl groups other than acetyl, such as formyl, crotonyl, and myristoyl. In this mini-review, I will first integrate the current literature coverage on the non-histone substrates and the catalytic deacylation (beyond deacetylation) of the zinc-dependent HDACs, which will be followed by an address on the functional interrogation and pharmacological exploitation (inhibitor design) of the zinc-dependent HDAC-catalyzed deacylation (beyond deacetylation).
Chromenes - A Novel Class of Heterocyclic Compounds: Recent Advancements and Future Directions
Authors: Chaudhary Anurag , Singh Kalpana , Verma Nishant , Kumar Sachin , Kumar Deepak , Sharma Prince Prashant 
Published: April 2022

Abstract:Chromenes are an important class of oxygen-containing heterocyclic compounds with intriguing biological activity, a simple structure with mild adverse effects. Chromenes are abundantly found in nature in the form of alkaloids, tocopherols, flavone, and anthocyanins. The Chromene nucleus is an important moiety for the discovery of new drug candidates. Chromene derivatives have shown various pharmacological activities like antiviral, anticancer, anti-inflammatory, antitumour, antimicrobial, antiproliferative, anticholinesterase, EPR-1 (Effector cell Protease Receptor-1) antagonist and MAO (Mono-Amine Oxidase) inhibitors. In SAR (Structure Activity Relationship) studies with chromene nucleus, it was found that 4-aryl moiety, 3-cyano group, and 2-amino group are essential for the cytotoxic activity. Substitution at the 7th position with electron donating group enhances the pharmacological activity whereas the electron withdrawing group decreases the pharmacological activity. Structural modifications at the chromene ring, middle aliphatic portion, and terminal aromatic ring yielded more potential 5-HT1A (5-Hydroxytryptamine 1A) receptor affinity and antidiabetic activity. Chromenes with cyclic secondary amine and 4-hydroxy phenyl substituents yielded potent antimicrobial compounds. This review summarizes the importance of chromenes in rational drug design and the development of novel molecules with a variety of pharmacological activities.
Analysis of Prognostic Risk Factors for Ischemic Stroke in China: A Multicentre
Retrospective Clinical Study; A National Survey in China
Authors: Wang Yongjun , Cao Yuting , Chen Ying , Zhang Xiaoli 
Published: April 2022

Background:
Stroke is a serious disease that threatens human health both in China and
worldwide. Identifying and establishing its risk factors are prerequisites for intervention and evaluation
of prognosis. Over the years, risk factors, such as age, diabetes, and hypertension, have gradually
been established. However, at present, there is no consensus on the influence of sex on the prognosis
of ischaemic stroke.

Aims:
The aims of our research was to analyse the correlation between sex and poststroke prognosis
based on the results of the Third China National Stroke Registry [CNSR-III], as well as the influence
of other risk factors that may be confounded by sex on ischaemic stroke and potential interventions.

Methods:
The CNSR-III recruited 14146 acute ischaemic stroke [AIS] patients between 2015 and
2018. Our study included 13,972 patients who had complete follow-up information. This research
analysed basic information, socioeconomic status, lifestyle habits, medical history, and poststroke
prognosis.

Results:
There was a conspicuous relationship between sex and functional prognosis, stroke recurrence
and all-cause death due to ischemic stroke in univariate analysis. Male stroke patients had a
better prognosis than female patients. In multivariate analysis, we found that age, atrial fibrillation
[AF], diabetes, hypertension and the severity of stroke had adverse effects on ischemic stroke prognosis.
After adjustment for other risk factors, the functional prognosis of female patients at 3 months
was worse than that of male patients [odds ratio [OR] 1.16, 95% confidence interval [CI], 1.025-
1.314]. Sex had a nonsignificant association with stroke recurrence at 3 months [hazard ratio [HR]
1.141, 95% CI, 0.975-1.336]. Furthermore, compared to male patients, female stroke patients had a
lower cumulative death rate at 12 months [HR 0.777, 95% CI, 0.628-0.963].

Conclusion:
Our study identified sex differences in stroke-related disability, recurrence, and death
and attempted to explain the causes of these differences. Our study clearly showed that a large proportion
of this difference could be attributed to age, socioeconomic factors, lifestyle habits, and
medical history, confounded by sex differences rather than sex per se.
Targeting the HIV-1 Tat and Human Tat Protein Complex through Natural
Products: An In Silico Docking and Molecular Dynamics Simulation
Approach
Authors: Kumar Vipin , Mishra Ayushi , Singh Vinay Kumar , Singh Anchal 
Published: April 2022

Background:
Tat protein is considered essential for substantial HIV-1 replication, and is also
required to break HIV-1 latency, resulting in productive HIV replication. The multifaceted regulatory role
of HIV Tat and the fact that it is expressed in the early stages of HIV infection justify its potential as an
anti-HIV drug target.

Objective:
The present study was undertaken with the aim to target HIV-1 Tat protein with natural compounds
which could help in identifying potential inhibitors against HIV-1 Tat.

Methods:
In this study, we compared the binding of Tat protein and Human P-TEFb Tat protein complex
(TPC) with phyto-steroids and terpenes to evaluate their potential for HIV-1 treatment. The docking ability
of plant products with HIV-1 Tat and TPC was studied with respect to dissociation constant, geometric
shape complementary score, approximate interface area, and binding energy using Patch dock and
YASARA. Molecular dynamics simulation was set up to investigate the interactions of the natural compounds
with Tat protein and human tat protein complex (TPC).

Results:
The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A
with Tat and TPC were comparable to antiretroviral drugs, Maraviroc and Emtricitabine. The natural
products, Diosgenin, Ginkgolide A and Catharanthine, showed the highest binding energy and were stable
with Tat protein and TPC in the entire MD simulation run.

Conclusion:
The natural products, Diosgenin, Ginkgolide A and Catharanthine, showed highest binding
energy and were stable with Tat protein and TPC in the entire MD simulation run. The binding energy
and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC were comparable
to antiretroviral drugs, Maraviroc and Emtricitabine.
Safety and Effectiveness of Sorafenib in the Treatment of Advanced Hepatocellular
Carcinoma
Authors: Vijayan Meenu , Prasanthan Ardra Thottarath , Raju Dona , Vinayakumar Syamaprasad Thachethukunnil , Jacob Mary , Chandran Anand , Keechilatu Pavithran 
Published: April 2022

Background:
Hepatocellular carcinoma (HCC) is the most prevalent kind of primary liver
cancer and a significant cause of cancer-related mortality across the world. Sorafenib is considered
the approved drug of choice in advanced HCC, which is an oral multikinase inhibitor with effective
antiproliferative and antiangiogenic effects. In India, there is currently insufficient data on the safety
and efficacy of sorafenib in the treatment of HCC.

Objective:
The study aims to evaluate the safety and effectiveness of sorafenib therapy in advanced
HCC.

Methods:
A prospective study of 66 patients administered with sorafenib for advanced HCC
between June 2016 and May 2017 was carried out in a single center with a mean follow-up of 3
months. The adverse events (AEs) were graded using the Common Terminology Criteria for
Adverse Events (CTCAE), version 4.0. Effectiveness was analyzed based on alpha-fetoprotein
(AFP) levels from laboratory findings. The median age was 63 years (range 61-70), with the male to
female ratio of 16:1.

Results:
The most commonly observed adverse events were fatigue (31.81%), hand-foot syndrome
(24.24%), and diarrhea (24.24%). A statistically significant decline in AFP levels was observed with
sorafenib treatment (p= <0.001).

Conclusion:
Sorafenib appears to be beneficial for individuals with advanced HCC, regardless of the
baseline condition.
Enhancement of Drug Penetration Rate by Enriching Skin Hydration: A
Novel Amalgamation of Microemulsion and Supersaturation
Authors: Chavda Dipika , Shukla Atindra , Soni Tejal 
Published: April 2022

Background:
The evolving need and facilitation of topical formulations have risen in the
present era. Topical industries are continually striving to satisfy patients with newer and innovative
products. However, dry skin is the critical factor contributing to drug penetration into the skin.

Objective:
The current research aims to develop cost-effective and commercially feasible industrial
scale microemulsion of wheat germ oil to enrich skin hydration, enhancing the drug permeation rate.

Methods:
The Pseudo-ternary phase diagram was constructed for screening of microemulsion components.
Wheat germ oil containing O/W microemulsion was prepared and evaluated for physicochemical
parameters, thermodynamic stability study, globule size determination, enhancement of skin hydration,
and skin permeation rate by ex vivo study.

Results:
The wheat germ oil containing microemulsion was prepared by incorporating tween 20 [surfactant]
and ethanol [co-surfactant]. All physicochemical parameters were in the ideal range. Following
the thermodynamic stability study, the TEM study showed globule size of optimized microemulsions
in the range of 69.64 nm to 84.42 nm. The skin moisture tester showed a high hydration level for
more than eight hours. An Ex vivo study revealed higher drug flux [Jss] of Pomegranate peel Extract
[17.99 μg/cm2/h] with an enhancement ratio of 1.69.

Conclusion:
The topical formulation application has become challenging for researchers due to the
skin's dryness and lower water content. However, the developed WGO microemulsion aids more penetration
and is helpful in achieving higher drug flux. In addition, it is a cost-effective, easy to prepare,
and patient-friendly drug delivery system.
Nurse-led and Interdisciplinary Secondary Cardiovascular Prevention
Programmes: Spanish Cohort of the EUROACTION Project
Authors: Buigues Cristina , Trapero Isabel , Velasco Jose Antonio , Salvador-Sanz Antonio , Jennings Catriona , Wood David , Queralt Ana 
Published: April 2022

Background:
Cardiovascular prevention and rehabilitation programmes (CVPRP) are a
preventive tool, which can reverse unhealthy behaviours and improve risk factor management.
They have been successfully implemented in a variety of settings in patients with coronary heart
disease (CHD).

Objective:
The objective of this study is to evaluate an interdisciplinary and nurse-led
cardiovascular prevention and rehabilitation programme in patients with coronary heart disease.

Method:
Six pairs of hospitals were randomised between intervention (INT) and usual care (UC)
patients. The interdisciplinary team in the intervention hospital carried out a 16-week CVPRP to
reach European risk factor goals. The trial is registered as ISRCTN 71715857.

Results:
The proportion of patients achieving European cardiovascular recommendations in Spain
increased in the intervention hospital, mainly regarding fruit and vegetable consumption (INT 98%
vs. UC 53%, p<0.001), oily fish consumption (INT 42% vs. UC 19.5%, p<0.001), self-reported
physical activity (INT 31% vs. UC 12.4%, p=0.04), blood pressure (INT 69% vs. UC 47.1%) p<
0.05) and LDL concentrations (INT 86.1% vs. UC 67.6%, p=0.04).

Conclusion:
The EUROACTION nurse-led model of CVPR programme has shown that
therapeutic goals in cardiovascular disease prevention are affordable and sustainable in everyday
clinical practice. EUROACTION model adapted in Spain has produced a healthier lifestyle.

Clinical Trial:
Trial registration No. ISRCTN 71715857.
Interventions to Promote Rehabilitation Programmes for Youth with Violent Behaviours in Limpopo Province: A Systematic Literature Review
Authors: Ramakulukusha Tshilidzi O. , Babalola Sunday S. , Mashau Ntsieni S. 
Published: April 2022

Background:
A rehabilitation strategy aims to reshape the individual and prepare them to enter society with a different state of mind and start a new life after incarceration.

Objective:
The purpose of this systematic literature review was to identify and describe the intervention strategies to promote rehabilitation programmes for youth with violent behaviours, guided by Rodger’s evolutionary concept analysis framework.

Methods:
A comprehensive database search was conducted from 2010 to 2020. The review focused on quantitative and qualitative studies and reports obtained from GOOGLE SCHOLAR, SABINET, SAGE, EBSCO-HOST, and SCIENCE DIRECT. Keywords and search strategies were also taken into consideration. The researchers systematically reviewed the literature, and 250 articles and 25 reports were obtained; their content was screened for relevance, and 50 articles and 11 reports were found to be suitable and relevant; these were then reviewed. A thematic analysis was performed to identify antecedents, attributes, and consequences of rehabilitation on youth with violent behaviours. The study findings were then used to inform the development of the conceptual framework.

Results:
The results show that antecedents of these rehabilitation strategies on violent youth behaviours include family structure, increased bullying due to gangs, and gender and environmental factors. The identified attributes were motivation, contextual differences, transformation, opportunity, and ineffective rehabilitation programmes in addressing violent behaviours in youths.

Conclusion:
Youth is regarded as the most vulnerable group in society, holding a high percentage of the population. As a result, it is always vital to protect them.
Optimization of Site-exploration Programs in Slope Designs Using 3D
Conditional Random Fields
Authors: Ou-Yang Jia-Yi , Liu Yong , Chen Guan 
Published: April 2022

Background:
In situ soil properties exhibit inherent spatial variability, which is often
described by a 3D random field. Soil properties at particular portions are available by site investigation.
Wider site investigation scope provides a more accurate description of the geologic profile.
However, limited by budget, choosing an effective site exploration scope is of significance.

Objective:
This study introduces a framework to determine the optimal site investigation strategy in
the 3D domain, which yields the lowest mean risk of slope designs.

Method:
The mean risk of slope designs is considered to be a function of the costs of site investigation,
under-design, and over-design. The unconditional random fields are generated by the spectral
representation method initially. Subsequently, the sampled data are incorporated into the random
fields via the Kriging algorithm, and the conditional random fields are simulated. A 3D undrained
slope is evaluated for illustration.

Results:
The effects of sampling locations and spacing on the risk of slope designs are examined.
The results indicate that the optimal sampling location is close to the zone where slope failure may
occur. Moreover, there exists an optimal sampling spacing that minimizes the mean risk of slope
designs.

Conclusion:
This investigation can provide guidance for determining the optimal site exploration
programs on the 3D domain with knowledge of the associated risks.
Natural Approach in Osteoarthritis Therapy
Authors: Grigore Alice , Vulturescu Virginia 
Published: April 2022

Abstract:
Osteoarthritis (OA) is the most common joint disease worldwide, and its rising prevalence is supported by factors such as obesity and sedentariness. At the molecular level, it is considered an inflammatory disease that leads to the destruction of articular cartilage. Effective therapy to end the degenerative process of arthritis remains elusive, and most therapeutic tools prevent the progress or alleviate the symptoms. By now, medicines for OA are available for oral, topical, or intra-articular (IA) therapy and include analgesics, nonsteroidal anti-inflammatory drugs, corticosteroids, and hyaluronic acid. Compared with conventional oral administration, IA therapy has multiple advantages in terms of bioavailability, efficacy, and toxicity. This review aims to study the underlying beneficial effects of herbal medicine in OA therapy and to open new research perspectives. Herbal medicine administered orally or topically exhibits pharmacological properties that could be relevant for their beneficial effect in OA, mainly anti-inflammatory and antioxidant effects. There are few studies regarding IA injections of plant extracts/ compounds and none related to any combination with agents already used in the clinic. Designing natural pharmaceutical formulations with increased bioavailability that are safe, lack side effects, and are specifically tested, would be a plus for research on medicinal plants and a novelty for the clinic.
IMPLEMENTASI KEBIJAKAN KARTU INDONESIA PINTAR (KIP) DALAM UPAYA MENGURANGI ANAK PUTUS SEKOLAH DI SMP N 1 PONCOWARNO
Authors: Saputri Vikin Ade 
Published: April 2022

The Smart Indonesia Card Policy in reducing the number of children who drop out of school is not optimal. The purposes of this research are to describe: 1) The implementation of the Smart Indonesia Card Policy in reducing the number of children who drop out of school at SMP N 1 Poncowarno, 2) The impact of the implementation of the Smart Indonesia Card in an effort to reduce the number of children who drop out of school at SMP N 1 Poncowarno, and 3) Factors that support and hinder the implementation of KIP policies at SMP N 1 Poncowarno.This research uses a descriptive qualitative approach. Data collection techniques are interviews, observation and documentation. The subjects of this research were staff of the Kebumen district office planning, school principals, school KIP managers, students of KIP recipient, parents of KIP recipients, and students who had dropped out of school. The data analysis technique used Milles and Huberman’s model, namely interactive analysis. The data validity used source and technique triangulation.The results showed: 1) Smart Indonesia Cards are communicated through regular socialization. Supporting equipment resources are computers and Wi-Fi. The number of managers at school is deemed insufficient. School plays a role as the person in charge. 2) KIP has not maximally reduced APS. 3) Supporting factors: good communication, coordination, socialization and cooperation among policy implementers, as well as supporting facilities. The inhibiting factors are lack of management personnel, student negligence and not being on target. Keywords: Policy Implementation, Smart Indonesia Card, children who drop out of school
EVALUASI SISTEM REAL TIME ONLINE DALAM PROGRAM PENERIMAAN PESERTA DIDIK BARU DI DINAS PENDIDIKAN KOTA YOGYAKARTA
Authors: Firlani Heru Dyah 
Published: April 2022

This study aims to describe the evaluation of the Real-time Online system in the new student admission program at the Yogyakarta City Education Office. The method in this study is a qualitative descriptive study with the CIPP evaluation model. The data collection techniques used in this study are documentation, interviews, and observations. The research data were analyzed using the Miles and Huberman model. The validity test of the data used triangulation of sources and techniques. The results of the study show that: (1) Context aspect, policies for implementing the new student admission program with the Real-Time Online system in the Yogyakarta City Education Office are relevant and have referred to Yogyakarta Mayor regulation number 24 of 2018. (2) Input aspect, the availability of human resources has been fulfilled. The completeness and feasibility of infrastructure are still lacking, such as a network that had problems. (3) The process aspect, the implementation of the program is by following the guidelines for the admission of new students to the education, it is being objective, accountable, transparent, and non-discriminatory. (4) Aspects of results, the data of students who register with the capacity for elementary schools have been met, however, for junior high school there are still empty seats. Keywords: real time online system, the new students admission