bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transition Towards Antibiotic Hybrid Vehicles: The Next Generation
Antibacterials
Authors: Kuppusamy Rajesh , Browne Katrina , Suresh Dittu , Do Rosario Romano Maximo , Chakraborty Sudip , Yang Sandy , Willcox Mark , Black David , Chen Renxun , Kumar Naresh 
Published: June 2022

Abstract:
Antibiotic resistance is a growing global health problem when the discovery and development of novel antibiotics are diminishing. Various strategies have been proposed to address the problem of growing antibacterial resistance. One such strategy is the development of hybrid antibiotics. These therapeutic systems have been designed for two or more pharmacophores of known antimicrobial agents. This review highlights the latest development of antibiotic hybrids comprising of two antibiotics (cleavable and non-cleavable) and combinations of biocidal and novel compounds to treat bacterial infections. The approach of dual-acting hybrid compounds has a promising future to overcome drug resistance in bacterial pathogens.
IGF2BP3 Worsens Lung Cancer through Modifying Long Non-coding
RNA CERS6-AS1/microRNA-1202 Axis
Authors: Yan An , Song Xiaowei , Liu Bao , Zhu Kaibin 
Published: June 2022

Background:
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) can epigenetically regulate lung cancer progression, but its regulatory mechanism in the disease lacks sufficient exploration.

Objective:
The study was conducted to probe the regulatory function of IGF2BP3 in lung cancer via modulating long non-coding RNA CERS6-AS1/microRNA-1202 (CERS6-AS1/miR-1202) axis.

Methods:
Clinical samples were collected to evaluate IGF2BP3, CERS6-AS1, miR-1202 and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels. The interactions among IGF2BP3, CERS6-AS1, miR-1202 and GDPD5 were assessed. IGF2BP3-, CERS6-AS1-, and miR-1202-related vectors were transfected into lung cancer cells to determine cell biological functions. Cell tumor formation ability was further detected in vivo.

Results:
High expression of IGF2BP3, CERS6-AS1 and GDPD5, and low expression of miR-1202 levels were witnessed in lung cancer tissues. Suppression of IGF2BP3 restrained lung cancer progression. IGF2BP3 positively modulated CERS6-AS1 to regulate miR-1202-targeted GDPD5. Inhibition of CERS6-AS1 or promotion of miR-1202 depressed lung cancer aggravation. CERS6-AS1 silencing or miR-1202 overexpression reversed the impacts induced by IGF2BP3 on lung cancer.

Conclusion:
IGF2BP3 facilitates the development of lung cancer cells via binding to the CERS6-AS1 promoter and down-regulating miR-1202, which may be related to GDPD5 upregulation.
Synthesis of β-Amino Carbonyl 6-(Aminomethyl)- and
6-(Hydroxymethyl)pyrazolopyrimidines for DPP-4 Inhibition Study
Authors: Chung Cheng-Yen , Tseng Ching-Chun , Li Sin-Min , Zeng Wei-Zheng , Lin Yu-Ching , Hu Yu-Pei , Jiang Wen-Ping , Huang Guan-Jhong , Tsai Henry J. , Wong Fung Fuh 
Published: June 2022

Background:
Type-2 diabetes is a chronic progressive metabolic disease resulting
in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors
had been conceived as a favorable class of agents for the treatment of type 2 diabetes due
to the minimal side effects.

Methods:
Sitagliptin is the first medicine approved for the DPP-4 inhibitor. Its structure
involved three fragments: 2,4,5-triflorophenyl fragment pharmacophore, enantiomerically
β-amino carbonyl linker, and tetrahydrotriazolopyridine. Herein, we are drawn to the
possibility of substituting tetrahydrotriazolopyridine motif present in Sitagliptin with a series
of new fused pyrazolopyrimidine bicyclic fragment to investigate potency and safety.

Results:
Two series of fused 6-(aminomethyl)pyrazolopyrimidine and 6-(hydroxymethyl)
pyrazolopyrimidine derivatives containing β-amino ester or amide as linkers
were successfully designed for the new DPP-4 inhibitors. Most fused 6-methylpyrazolopyrimidines
were evaluated against DPP-4 inhibition and selectivity capacity. Based
on research study, β-amino carbonyl fused 6-(hydroxymethyl)pyrazolopyrimidine possesses
the significant DPP-4 inhibition (IC50 ≤ 59.8 nM) and presents similar with Sitagliptin
(IC50 = 28 nM). Particularly, they had satisfactory selectivity over DPP-8 and
DPP-9, except for QPP.

Conclusion:
β-Amino esters and amides fused 6-(hydroxymethyl)pyrazolopyrimidine
were developed as the new DPP-4 inhibitors. Those compounds with a methyl group or
hydrogen in N-1 position and methyl substituted group in C-3 of pyrazolopyrimidine moiety
showed better potent DPP-4 inhibition (IC50 = 21.4-59.8 nM). Furthermore, they had
satisfactory selectivity over DPP-8 and DPP-9 Finally, the docking results revealed that
compound 9n was stabilized at DPP-4 active site and would be a potential lead drug.
Cannabinoids and Brain Damage: A Systematic Review on a Frequently
Overlooked Issue
Authors: Scopetti Matteo , Morena Donato , Manetti Federico , Santurro Alessandro , Fazio Nicola Di , D’Errico Stefano , Padovano Martina , Frati Paola , Fineschi Vittorio 
Published: June 2022

Background:
Although cannabinoid consumption represents a current social and health
problem, especially in a historical context characterized by an open orientation for recreational and
therapeutic purposes, risks regarding the neurotoxicity of such substances are frequently overlooked.

Objective:
The present systematic review aims to summarize the available evidence regarding the
mechanism of cannabinoids-induced brain damage as a substrate of neurological, psychiatric, and
behavioral effects. Another objective is to provide support for future investigations and legislative
choices.

Methods:
The systematic literature search through PubMed and Scopus and a critical appraisal of the
collected studies were conducted. Search terms were “(("Cannabinoids" OR "THC" OR "CBD")
AND "Brain” AND ("Damage" OR "Toxicity"))” in the title and abstracts. Studies were included
examining toxic effects on the brain potentially induced by cannabinoids on human subjects.

Results:
At the end of the literature selection process, 30 papers were considered for the present
review. The consumption of cannabinoids is associated with the development of psychiatric, neurocognitive,
neurological disorders and, in some cases of acute consumption, even death. In this sense,
the greatest risks have been related to the consumption of high-potency synthetic cannabinoids, although
the consumption of phytocannabinoids is not devoid of risks.

Conclusion:
The research carried out has allowed to highlight some critical points to focus on, such
as the need to reinforce the toxic-epidemiologic monitor of new substances market and the importance
of information for both medical personnel and general population, with particular attention to
the mostly involved age groups.
ceRNA Network Analysis Reveals AP-1 Transcription Factor Components
as Potential Biomarkers for Alzheimer’s Disease
Authors: Wei Rui , Hu Qi , Lu Yanjun , Wang Xiong 
Published: June 2022

Background:
Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting
the elderly, characterized by decreased cognitive function. Non-coding RNAs contribute to AD
pathogenesis.

Objective:
To identify potential therapeutic targets for AD, competing endogenous RNA (ceRNA)
networks were constructed using the hippocampus of 6-month-old amyloid precursor protein/
presenilin 1 double transgenic (APP/PS1) and wild-type mice.

Methods:
RNA-seq data (GSE158995), generated from the hippocampus of APP/PS1 and wild-type
mice, were analyzed with the limma R package to identify significantly differentially expressed
mRNAs and circRNAs (DEMs and DECs, respectively). DEM Gene Ontology (GO) and Kyoto Encyclopedia
of Genes and Genomes (KEGG) analyses were performed using Enrichr
(https://maayanlab.cloud/Enrichr/). Correlations between DEMs and DECs were determined using
the ggcorrplot R package. Main clusters and hub DEMs were selected using the STRING database
and Cytoscape software. ceRNA interactions were predicted with the miRTarbase and Starbase tools
and constructed with the ggalluvial R package and Cytoscape software. ceRNA networks were validated
using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western
blot.

Results:
198 DEMs and 90 DECs were differentially expressed in APP/PS1 vs. wild-type hippocampus.
DEM GO analysis revealed significant enrichment in transcription regulation, which was subdivided
into three main clusters: transcription regulation, synaptic plasticity, and protein refolding.
Within the transcription regulation cluster, AP-1 transcription factor components serve as hub genes.
The mmu_circ_0001787(circGLCE)/miR-339-5p/Junb and mmu_circ_0001899(circFAM120C)/
miR-181a-5p/Egr1 ceRNA networks were established based on qRT-PCR and Western blot analysis.

Conclusion:
Two AP-1 transcription factor component-related ceRNA networks, circGLCE/miR-
339-5p/Junb and circFAM120C/miR-181a-5p/Egr1, were constructed using a mouse model of AD.
These ceRNA networks may contribute to transcription regulation in AD and provide potential biomarkers
for AD diagnosis and treatment.
Synthesis and Biological Evaluation of Some New Chalcone Derivatives as
Anti-inflammatory Agents
Authors: Saini Pooja , Rehman Zia Ur , Kumar Sushil 
Published: June 2022

Aim:
The present research work aims to prepare a series of 1-(4-(2-(1H-indol-1-yl)-2-
oxoethoxy)phenyl)-3-phenylprop-2-en-1-one derivatives.

Method:
The major compound was achieved by the reaction of indole with chloroacetylchloride in
benzene afforded 2-chloro-1-(indoline-1-yl) ethanone which reacts o- hydroxy acetophenone in presence
of acetonitrile to form 2-(4-acetylphenoxy)-1-(1H-indol-1-yl)ethan-1-one then goes through aldol
condensation to give various final derivatives.

Results and conclusion:
After the synthesis of compounds, the synthesized compounds were characterized
by checking their solubility, melting point, thin layer chromatography, IR, 1HNMR spectral
data and elemental analysis. All of the prepared derivatives were evaluated for their anti-inflammatory
activity on wistar albino rats by following the carrageenan-induced Rat Hind Paw Edema model.
Nano-Based Drug Delivery of Anticancer Chemotherapeutic Drugs Targeting
Breast Cancer
Authors: Behl Akanksha , Chhillar Anil K. 
Published: June 2022

Background:
Chemotherapeutic drugs are principally intended to treat breast cancer. However, sooner or later in tumor drug resistance developed. These chemo drugs are effectual, but with numerous side effects. Breast cancer care may be extremely difficult since recurring cancer is frequently pre-treated with powerful agents, and cancer cells acquire high resistance to earlier therapies, necessitating the use of alternative and more powerful drugs. Nanoparticles(NPs) as a medication delivery technology can overcome medication resistance in breast cancer and significantly reduce the effective dose. The off-targeted nature of chemo drugs can be resolved by encapsulating or attaching chemo drugs in nanocarrier which targets specifically breast cancer cells.

Objectives:
In this review, we highlight various chemo drugs for breast cancer and their encapsulation or bioconjugation with nanoparticles for its targeted delivery.

Conclusion:
Nanoparticles may subsist valuable abet in breast cancer management in this regard. Given that traditional chemotherapy, approaches have been demonstrated to have several side effects and defects during treatment, the NPs-mediated Drug delivery mechanism is a possible contender for replacement as a new technique.
A Comprehensive Review on Journey of Pyrrole Scaffold Against Multiple Therapeutic
Targets
Authors: Mir Reyaz Hassan , Mir Prince Ahad , Mohi-ud-din Roohi , Sabreen Saba , Maqbool Mudasir , Shah Abdul Jalil , Shenmar Kitika , Raza Syed Naeim , Pottoo Faheem Hyder 
Published: June 2022

Abstract:
Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes.
Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic
molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological
molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold
is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered
heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds.
Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial,
antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological
profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore
it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives
against multiple therapeutic targets.
Antihypertensive Activity of Prunus armeniaca in Hypertensive Rats
Authors: Eddouks Mohamed , Bouadid Ismail , Akdad Mourad 
Published: June 2022

Aims:The goal of this work was to evaluate the antihypertensive activity of Prunus armeniaca.Background:Prunus armeniaca is known for its beneficial medicinal properties.Objective:This study aimed to evaluate the effect of the aqueous extract of Prunus armeniaca L. (P. armeniaca) leaves (PAAE) on arterial blood pressure in normotensive and hypertensive rats.Materials and Methods:In the in vivo examination, N-omega-Nitro-L-arginine methyl ester hydrochloride( L-NAME)-induced hypertensive and normotensive rats received PAAE (160 and 100 mg/kg) orally for the acute experiment spanning 6 hours and for seven days for the subchronic treatment; their blood pressure parameters were also evaluated. In the in vitro experiment, isolated intact thoracic aortic rings were precontracted with KCl (80 mM) and epinephrine (EP) (10 μM), and vascular dilatation was assessed.Results:PAAE lowered blood pressure parameters in L-NAME-induced hypertensive without affecting normotensive rats following oral administration, suggesting that PAAE possesses an antihypertensive effect. In addition, PAAE (0.25-1 mg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted by EP (10 μM), and this effect was especially reduced in the presence of glibenclamide or nifedipine. However, PAAE (0.25-1 mg/mL) had only a minimal vasorelaxant effect on thoracic aortic rings precontracted by KCl (80 mM).Conclusion:The results demonstrate that the P. armeniaca aqueous extract possesses potent antihypertensive and vasorelaxant activity, and its vasorelaxant activity seems to be mediated through the opening of ATP-sensitive K+ channels and inhibition of L-type calcium channels.
Small-Signal Stability Improvement of Grid Integrated DFIG and SOFC
System with SSSC-POD Using Coordinated Optimization Approach
Authors: He Ping , Jin Haoran , Fang Qiyuan , Qi Pan , Gong Zhijie , Ji Yuqi 
Published: June 2022

Background:
Focusing on the stability problems brought by integrated wind power and fuel cell, the objective of this paper is to analyze small-signal stability and improvement of a hybrid renewable energy system connected with doubly-fed induction generators (DFIGs) and solid oxide fuel cells (SOFCs) energy with the static series synchronous compensator (SSSC) and power-oscillation damper (POD).

Methods:
For this purpose, a SSSC-POD controller is designed and the state-space representation of such a hybrid power system for modal analysis is developed. Then an approach of coordination and optimization of SSSC-POD parameters based on genetic algorithm (GA) and modal analysis is proposed to further improve the power system small-signal stability.

Results:
Several designed scenarios, including changing the tie-line power, POD input signal and SOFC power output, are considered in IEEE two-area system to test the proposed method through small-disturbance eigenvalue analysis and time-domain simulations.

Conclusion:
Simulation results demonstrate that the proposed approach can effectively suppress the local and inter-area oscillations and improve power system stability.
Associations Between Family Member Involvement and Outcomes of Patients Admitted to the Intensive Care Unit: Retrospective Cohort Study
Authors: Gray Tamryn F , Kwok Anne , Do Khuyen M , Zeng Sandra , Moseley Edward T , Dbeis Yasser M , Umeton Renato , Tulsky James A , El-Jawahri Areej , Lindvall Charlotta 
Published: June 2022

Background
Little is known about family member involvement, by relationship status, for patients treated in the intensive care unit (ICU).

Objective
Using documentation of family interactions in clinical notes, we examined associations between child and spousal involvement and ICU patient outcomes, including goals of care conversations (GOCCs), limitations in life-sustaining therapy (LLST), and 3-month mortality.

Methods
Using a retrospective cohort design, the study included a total of 858 adult patients treated between 2008 and 2012 in the medical ICU at a tertiary care center in northeastern United States. Clinical notes generated within the first 48 hours of admission to the ICU were used with standard machine learning methods to predict patient outcomes. We used natural language processing methods to identify family-related documentation and abstracted sociodemographic and clinical characteristics of the patients from the medical record.

Results
Most of the 858 patients were White (n=650, 75.8%); 437 (50.9%) were male, 479 (55.8%) were married, and the median age was 68.4 (IQR 56.5-79.4) years. Most patients had documented GOCC (n=651, 75.9%). In adjusted regression analyses, child involvement (odds ratio [OR] 0.81; 95% CI 0.49-1.34; P=.41) and child plus spouse involvement (OR 1.28; 95% CI 0.8-2.03; P=.3) were not associated with GOCCs compared to spouse involvement. Child involvement was not associated with LLST when compared to spouse involvement (OR 1.49; 95% CI 0.89-2.52; P=.13). However, child plus spouse involvement was associated with LLST (OR 1.6; 95% CI 1.02-2.52; P=.04). Compared to spouse involvement, there were no significant differences in the 3-month mortality by family member type, including child plus spouse involvement (OR 1.38; 95% CI 0.91-2.09; P=.13) and child involvement (OR 1.47; 95% CI 0.9-2.41; P=.12).

Conclusions
Our findings demonstrate that statistical models derived from text analysis in the first 48 hours of ICU admission can predict patient outcomes. Early child plus spouse involvement was associated with LLST, suggesting that decisions about LLST were more likely to occur when the child and spouse were both involved compared to the involvement of only the spouse. More research is needed to further understand the involvement of different family members in ICU care and its association with patient outcomes.
Utilization of Coffee Pulp Waste Composted with Cellulolytic Actinomycetes to Enhance Chili Plant Growth
Authors: Fatmawati Umi , Sari Dewi Puspita , Indrowati Meti , Santosa Slamet , Wiraswati Sri Martina , Harlita Harlita 
Published: June 2022

The abundant volume of coffee bean pulp as a by-product of the post-harvest processing is an important source of soil organic matter if it is properly handled. The alternative way to use coffee bean pulp waste to reduce the impact of environmental pollution is composting. This study aims to determine the ability of actinomycetes to degrade coffee pulp, to identify the physical and chemical characteristics of coffee pulp compost, and to evaluate the effect of coffee pulp compost on chili plant growth. The results showed that 7 isolates of actinomycetes were able to hydrolyze coffee pulp in vitro with a hydrolytic index of 1.7-3.81. The treatment of coffee pulp compost with the addition of a starter of cellulolytic actinomycetes (P2) at the end of the three-week incubation period showed the highest organic N (25 mg/kg), P (7.05 mg/kg), and K (33 mg/kg), t compared to other treatments. The effect of giving coffee pulp compost towards the growth of chili plants shows that the coffee pulp composted with zeolite 5% (w/w) increased the height of the chili plants by 37.6%, while in coffee pulp composted by cellulolytic actinomycetes 5% (v/w) increased the number of leaves by 96% and plant biomass by 25%. Based on the results of this research, coffee pulp compost has the potential to be used as biological fertilizer to increase plant growth, both composted by zeolite and cellulolytic actinomycetes
Strategi Adaptasi Masyarakat selama masa Pandemi Covid-19: Studi di Desa Tegaltirto Kecamatan Berbah Kabupaten Sleman
Authors: Rahman Fathin Aulia , Ruslanjari Dina , Giyarsih Sri Rum 
Published: June 2022

Dalam berbagai studi sering menunjukkan bahwa dalam situasi krisis berbagai bentuk kemampuan manusia dalam beradaptasi atau strategi bertahan hidup untuk keluar dari kesulitan. Hal ini terbukti ketika pandemi Covid-19 telah menyerang masyarakat seluruh dunia, termasuk Indonesia. Studi ini akan membahas dan menganalisis bagaimana strategi dan bentuk adaptasi masyarakat selama pandemi Covid-19, secara khusus di Desa Tegaltirto,Kecamatan Berbah, Kabupaten Sleman. Desa Tegaltirto menarik untuk diteliti karena desa ini menjadi akses utama dan jalur perdagangan antar kecamatan dan kabupaten. Sebagian besar masyarakatnya bekerja pada sektor informal yang rentan terhadap perubahan dan krisis. Penelitian ini merupakan jenis penelitian kuantitatif dengan metode survei dengan sampel populasi diambil di Dusun Kadisono, Sompilan dan Semoya dengan teknik sampling menggunakan stratified random sampling, jumlah sampel proporsional dengan jumlah populasi.Teknik analisis data menggunakan metode deskriptif kuantitatif. Hasil penelitian menunjukkan seluruh rumah tangga di Desa Tegaltirto menerapkan strategi bertahan hidup, bentuk strategi paling banyak dilakukan yaitu melakukan kontrol terhadap pemasukan dan pengeluaran. Pada strategi konsolidasi mayoritas rumah tangga menerapkan strategi menyesuaikan pengeluaran antar waktu dengan cara mengambil tabungan, mencari pinjaman, menggadai barang dan/atau menjual aset yang dimiliki. Sedangkan rumah tangga yang lainnya menerapkan strategi akumulasi dengan meningkatkan pemasukan melalui peningkatan produksi usaha yang dimilikinya
Health-Seeking Behavior of People in Five Sub-Districts in Karawang Regency
Authors: Azis Iqbal Ainnun , Arisanti Nita , Mariani Helni , Agustian Dwi , Mayasari Wulan , Sujatmiko Budi 
Published: June 2022

Background: Health-seeking behavior is an individual’s action to maintain and improve their degree of health and/or search for treatment, and it is influenced by many factors. The objectives of this study were to identify the preferences and reasons of people to visit healthcare facilities.Methods: This study was a descriptive study, conducted on November 5th 2019 at five sub-districts in Karawang Regency. Data were collected from all respondents using a guided questionnaire by trained enumerators. The respondents who did not complete the questionnaire were excluded from this study. Data were analyzed using Microsoft Office Excel 2013 and presented in percentages.Results: Out of 430 subjects, 18.6% were male and 81.4% were female, who were mostly in the age range of ≥ 18 years (99.5%). The sub-district health community center (Puskesmas) was the healthcare facilities most frequently visited and most preferred (39.7% and 40.9%), followed by a private clinic (21.3% and 22.3%) and a midwife (18.1% and 17.9%). Additionally, accessibility, affordability of the treatment cost, and waiting time were the main factors that influence people’s decision in using the healthcare facilities.Conclusion: The sub-district health community center was the healthcare facilities most frequently visited and most preferred by respondents. Accessibility, cost affordability, and waiting time were the factors that influence people’s decision in using the healthcare facilities.