bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis and Spectroscopic Characterizations of Medicinal Hydrazide
Derivatives and Metal Complexes of Malonic Ester
Authors: Parveen Sajidah , Shah Habib-Ur-Rehman , Ashfaq Muhammad , Naseem Hafiza Ammara , Ahmad Khalil , Aziz Tariq , Rauf Abdul 
Published: December 2021

Background:
A new series of malonic acid-based hydrazide derivatives (BPMPDH, 2HPMPDH, 3HPMPDH, 4HPMPDH, DMPDH) are successfully synthesized by the reaction of malonic ester hydrazide with various substituted aldehydes like salicylaldehyde, benzaldehyde, 4-hydroxy benzaldehyde, 3-hydroxy benzaldehyde and formaldehyde)

Methods:
metal complexes of prepared hydrazide derivatives were prepared using metals like Cu+2, Zn+2 and Ni+2 via a mild, efficient and convenient method. Newly synthesized compounds were characterized by IR, NMR (1H & 13C), UV/VIS and mass spectrometry. The presence of –C=N- peak at 1600-1700 cm-1 with the absence of NH2 peak at 3500 cm-1 in FTIR spectra. In 1HNMR peak at, 11.00-13.00 ppm for –OH protons and 7.00-9.50 ppm for –NH verified the synthesis of new hydrazide derivatives. The presence of a C-OH sharp peak at 180-190 ppm, a C=O peak at 160-170 ppm and a C=N peak at 140-150 ppm confirmed synthesis. In mass spectra, the molecular ion peaks at 308 m/z, 340 m/z and 156 m/z confirmed synthesis. Synthesized compounds have also been analyzed for their antioxidant, antibacterial, antifungal, chymotrypsin and tyrosinase inhibition activities

Result and Conclusion:
The results revealed that the 2HPMPDH, 3HPMPDH, 4HPMPDH and their Cu+2 and Zn+2 metal complexes showed more successful inhibition against standard drugs, based on structure activity relationship.
The Inhibitory Effect of Hydroalcoholic Extract from the Algerian Echium trygorrhizum Pomel Roots on α-amylase Activity
Authors: Nouri Allaoua , Gasmi Lakhder , Bensouici Chawki , Harzallah Daoud , Khennouf Seddik , Dahamna Saliha 
Published: December 2021

Background:Species of Echium trygorrhizum Pomel are used traditionally in Algeria folk medicine for the treatment of Diabetes, Jaundice and Tonsillitis. To our knowledge, no previous study has been conducted on the pharmacological activities of this species.Objective:The objective of the present research was to evaluate the content of polyphenols, flavonoids and condensed tannins compounds and to assess in vitro the antioxidant activity and the inhibitory effect of the hydroalcoholic extract of this plant on α-amylase activity, an enzyme responsible for digestion of carbohydrate before the process of intestinal absorption.Methods:Polyphenols, flavonoids and condensed tannins were evaluated spectrophotometrically using Folin-Ciocalteu, the Aluminum chloride and vanillin methods, respectively. The antioxidant activity using DPPH radical scavenging, ABTS, Ferric reducing antioxidant power and β-carotene bleaching tests and the assessment of in vitro α-amylase inhibitory potential by an Aspergillus oryzae α- amylase have been studied.Results:The hydroalcoholic crude extract was able to inhibit the α-amylase enzyme in vitro, with an IC50 of 0.56 ± 0.044 mg/ml, in addition, the contents of polyphenols and flavonoids were found to be 157.403 ± 0.835 μg GAE/mg extract and 30.156±2.634μg Q E / mg extract, respectively, Whereas the amount of tannins was 65.293 ± 0.883μg Cat E/ mg of dry extract.Conclusion:The present study revealed that the extract is rich in phenolic compounds, which play a really important role in the scavenging of free radicals. The inhibitory capacity of hydroalcoholic roots extract on Aspergillus oryzae α-amylase enzyme has been reported and might be used as a natural agent within the management of diabetes mellitus.
β-estradiol Induces Mitochondrial Apoptosis in Cervical Cancer through the Suppression of AKT/NF-κB Signaling Pathway
Authors: Zhang Enxin , Chen Jiaxu , Deng Lijuan , Huang Yuqing , Chen Shouguo , Lei Yuhe , Chung Chiwing , Chan Meiching , Chen Lei , Zhong Yinqin 
Published: December 2021

Background:
Cervical cancer is the fourth most prevalent gynecological cancer worldwide,
which threatens women's health and causes cancer-related mortality. In the search for effective
anticervical cancer drugs, we discovered that β-estradiol (E2), a potent drug for estrogen deficiency
syndrome treatment, displays the most potent cytotoxicity against HeLa cells.

Objective:
This study aims to evaluate the growth inhibitory effect of β-estradiol on HeLa cells and
explore its underlying mechanisms.

Methods:
CCK-8 assay was used to evaluate the cytotoxicity of 6 compounds against HeLa cells.
Flow cytometric analysis and Hoechst 33258 staining assay were performed to detect cell cycle arrest
and apoptosis induction. The collapse of the mitochondrial potential was observed by the JC-1
staining assay. The expression levels of proteins were examined by western blotting.

Results:
β-Estradiol, at high concentration, displays potent cytotoxicity against HeLa cells with an
IC50 value of 18.71 ± 1.57 μM for 72 h treatment. β-Estradiol induces G2/M cell cycle arrest
through downregulating Cyclin B1 and p-CDK1. In addition, β-estradiol-induced apoptosis is accompanied
by the loss of mitochondrial potential, activation of the Caspase family, and altered
Bax/Bcl-2 ratio. β-Estradiol markedly decreased the expression level of p-AKT and p-NF-κB.

Conclusion:
This study demonstrated that β-estradiol induces mitochondrial apoptosis in cervical
cancer through the suppression of AKT/NF-κB signaling pathway, indicating that β-estradiol may
serve as a potential agent for cervical cancer treatment.
Network Pharmacology-based Prediction and Verification of Shikonin for Treating Colorectal Cancer
Authors: Song Peng , Duan Dongzhu , Guo Wenjing , Wang Zefeng , Cui Qianfei , Shi Ling , Zhang Meiling 
Published: December 2021

Background:
Shikonin (SKN), a naturally occurring naphthoquinone, is a major active
chemical component isolated from Lithospermum erythrorhizon Sieb Zucc, Arnebia euchroma
(Royle) Johnst, or Arnebia guttata Bunge, and commonly used to treat viral infection, inflammation,
and cancer. However, its underlying mechanism has not been elucidated.

Objective:
This study aims to explore the antitumor mechanism of SKN in colorectal cancer (CRC)
through network pharmacology and cell experiments.

Methods:
SymMap database and Genecards were used to predict the potential targets of SKN and
CRC, while the cotargets were obtained by Venn diagram. The cotargets were imported into the
website of String and DAVID, constructing the protein-protein interaction (PPI) network, performing
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment
analyses, the Compound-Target-Pathway (C-T-P) network was generated by connecting potential
pathways with the corresponding targets.

Results:
According to the results of network pharmacological analysis, the cell experiments were
used to verify the key signal pathway. The most relevant target of SKN for the treatment of CRC
was PI3K/Akt signaling pathway. SKN inhibited CRC cells (HT29 and HCT116) proliferation, migration,
and invasion, and promoted cell apoptosis by targeting IL6 and inhibiting the
IL6R/PI3K/Akt signaling pathway. SKN promotes apoptosis and suppresses CRC cells’ (HT29
and HCT116) activity through the PI3K-Akt signaling pathway.

Conclusion:
This research not only provided a theoretical and experimental basis for more in-
-depth studies but also offered an efficient method for the rational utilization of a series of Traditional
Chinese medicines as anti-CRC drugs.
Synthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative
on a Heart Failure Model
Authors: Lauro Figueroa-Valverde , Maria López-Ramos , Francisco Díaz-Cedillo , Marcela Rosas-Nexticapa , Virginia Mateu-Armad Maria , Magdalena Alvarez-Ramirez , Tomas Lopez-Gutierrez , Idalia Arakachi-Cruz 
Published: December 2021

Background:
Several drugs with inotropic activity have been synthesized; however,
there is very little information on biological activity exerted by steroid derivatives in the cardiovascular
system.

Objective:
The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect
it exerts on left ventricular pressure and characterize its molecular interaction.

Methods:
The first stage was carried out through the synthesis of a steroid-pyridine derivative using
some chemical strategies. The second stage involved the evaluation of the biological activity of
the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the
absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin,
and nifedipine.

Results:
The results showed that steroid-pyridine derivative increased left ventricular pressure in a
dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only
by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced
by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological
activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP
concentration.

Conclusion:
It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative
involves a different molecular mechanism compared to other positive inotropic drugs. Therefore,
this steroid could be a good candidate for the treatment of heart failure.
Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats
Authors: Rezai Marzieh , Hajizadeh Mohammad Reza , Mahmoodi Mehdi , Torabizadeh Seyedeh Atekeh , Karimabad Mojgan Noroozi 
Published: December 2021

Background:
Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats

Methods:
I Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats

Results:
According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to significant reduction in the expression of BDNF and CREB genes at VTA as well as BDNF serum level compared with control group.

Conclusion:
It was concluded that methadone, like morphine, causes significant reduction in the expression of BDNF and CREB genes in brain VTA area of rat as well as BDNF serum level compared with control group.
Evaluation Effects of Quercetin on Streptozotocin-treated RINm5F
Pancreatic β-cells in vitro
Authors: Mazraesefidi Maryam , Sadeghipour Maryam Mohammad , Khorramdelazad Hossein , Mahmoodi Mahdi , Khoshdel Alireza , Fahmidehkar Mohammadali , Hosseiniara Reza , Hajizadeh Mohammad Reza 
Published: December 2021

Background and objectives:
Quercetin is a naturally occurring phenolic compound abundantly present in plants as a secondary metabolite. The purpose of this study was to investigate the effect of quercetin on improving RINm5F β-insulinemia cell viability, glucose-stimulated insulin secretion (GSIS), and cell insulin content in the presence or absence of streptozotocin (STZ).

Methods:
This experimental study was conducted on RINm5F β-insulinemia cell line. The cell viability was evaluated by MTT assay. The necrosis was confirmed by flowcytometry and insulin ELISA kit was used to measure the GSIS level and cell insulin content. It should be noted that for testing of cells by 50μM of quercetin, simultaneous treatment and pre-treatment of quercetin were performed in the presence of STZ (20mM).

Results:
The quercetin was able to improve the viability of RINm5F cells in the presence of STZ and to increase the GSIS level and cell insulin content under STZ and glucotoxic conditions

Conclusion:
The quercetin seems to have beneficial effects on β-cells, especially the synthesis and secretion of insulin. In addition to the therapeutic effect, given the low toxicity of this flavonoid and the results of this study, the quercetin as a preventive agent may play an important role in maintaining the health of β-cells in people at risk of diabetes.
Detection of Oncometabolite Nicotine Imine in the Nail of Oral Cancer Patients; Predicted as an Inhibitor of DNMT1
Authors: Dutta Anwesha Deep , Kumar Ajay , Lokhande Kiran Bharat , Mitruka Manmohan , Swamy K. Venkateswara , Pal Jayanta K. , Sarode Sachin C. , Sharma Nilesh Kumar 
Published: December 2021

Background:Nicotine-metabolized product nicotine imine is suggested to play a role in metabolic changes in oral cancer. There is a significant gap in the detection of oncometabolite nicotine imine in biological fluids and nails of oral cancer patients. Oncometabolites are designated as metabolites those are usually elevated in cancer cells over normal cells. Interestingly, a direct or indirect link is missing that establishes a role of nicotine imine in pro-cancer cellular events including global DNA hypomethylation, a potential metabolic-epigenetic axis in oral cancer.Methods:A novel vertical tube gel electrophoresis (VTGE) system assisted purification and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based identification of nicotine imine in the nails of oral cancer patients. Further, nicotine imine was evaluated for its molecular interactions with various methyltransferases including DNA methyltransferase 1 (DNMT1) by molecular docking and molecular dynamics (MD) simulations.Results:Data suggested the presence of nicotine imine in the nails of oral cancer patients. Molecular docking and MD simulations revealed a specific binding affinity by nicotine imine with DNMT1. Binding by nicotine imine is within the CXCC regulatory domain of DNMT1 including key residues as ARG690, PRO574, VAL658, PRO692 and ALA695. Similar binding residues are displayed by DNMT1 inhibitor 5'-Aza-2'-deoxycytidine.Conclusion :Nicotine imine is suggested as a predictive biomarker for oral cancer patients in nails and this finding is a first report. Molecular docking and dynamics simulation propose the role of nicotine imine as an inhibitor of DNMT1. This work supports the involvement of synergistic pro-tumor metabolic-epigenomic axis by nicotine imine that may contribute towards potential mutagenesis of normal squamous epithelium.
Virtual Endocrinology Care Emphasizing Data-Driven Insights and Continuous Engagement and Its Impact on Glycemic Outcomes in Patients With Uncontrolled Diabetes: A Real-world Retrospective Case Series
Authors: Wu Calvin C , Wu Karin C , José Aimée S , Novin Niloufar 
Published: December 2021

Background
Steady Health’s novel virtual care model incorporates continuous glucose monitoring (CGM) and a multidisciplinary approach to timely person-centered diabetes care.

Objective
This real-world retrospective case series explores the early glycemic outcomes of its patients with uncontrolled diabetes.

Methods
All patients of Steady Health who had an initial time in range (TIR) below 70% from their first 4 weeks of available CGM data and who had completed onboarding by February 2021 were included in this analysis. We compared the change in TIR, time below range, and average blood glucose from their first 4 weeks with their latest 4 weeks of available CGM data. Hemoglobin A1c (HbA1c) values at baseline and at the end of the study were also compared. Patients completed a questionnaire assessing their satisfaction with Steady Health’s intervention.

Results
A total of 53 patients (n=35, 66% with type 1 diabetes; n=44, 83% treated with insulin) were included in this analysis. This cohort had a median baseline TIR of 53.0% (IQR 40.9%, 61.7%) and saw a median change in TIR of +16.6% (IQR +6.0%, +27.9%; P<.001) over a median duration of care of 11 months, amounting to nearly 4 more hours spent between 70 to 180 mg/dL a day. Of the 27 patients who had both baseline and follow-up HbA1c results, their median baseline HbA1c was 8.6% (IQR 7.5%, 11.4%; 70 mmol/mol), while their median change in HbA1c was –1.2% (IQR –2.6%, –0.2%; P=.001). Importantly, these glycemic improvements were achieved with a median decrease in the time below range by –0.3% (IQR –1.1%, 0.0%; P<.001), regardless of whether patients were started on an automated insulin delivery system. A total of 40 (75.5%) patients improved TIR by ≥5%, and 27 (50.9%) achieved TIR≥70% by the end of the study. Glycemic improvements were greatest among patients with the lowest baseline TIR and those who collaborated most intensively with Steady Health’s clinicians. A total of 25 of these patients responded to a questionnaire assessing levels of satisfaction with their care, and all of them agreed that Steady Health had a positive impact on their diabetes management.

Conclusions
Our findings suggest that patients with uncontrolled diabetes can achieve significant glycemic improvements by working with a virtual multidisciplinary care team that uses CGM to provide continuous clinical feedback and support.
Health Care Analytics With Time-Invariant and Time-Variant Feature Importance to Predict Hospital-Acquired Acute Kidney Injury: Observational Longitudinal Study
Authors: Chua Horng-Ruey , Zheng Kaiping , Vathsala Anantharaman , Ngiam Kee-Yuan , Yap Hui-Kim , Lu Liangjian , Tiong Ho-Yee , Mukhopadhyay Amartya , MacLaren Graeme , Lim Shir-Lynn , Akalya K , Ooi Beng-Chin 
Published: December 2021

Background
Acute kidney injury (AKI) develops in 4% of hospitalized patients and is a marker of clinical deterioration and nephrotoxicity. AKI onset is highly variable in hospitals, which makes it difficult to time biomarker assessment in all patients for preemptive care.

Objective
The study sought to apply machine learning techniques to electronic health records and predict hospital-acquired AKI by a 48-hour lead time, with the aim to create an AKI surveillance algorithm that is deployable in real time.

Methods
The data were sourced from 20,732 case admissions in 16,288 patients over 1 year in our institution. We enhanced the bidirectional recurrent neural network model with a novel time-invariant and time-variant aggregated module to capture important clinical features temporal to AKI in every patient. Time-series features included laboratory parameters that preceded a 48-hour prediction window before AKI onset; the latter’s corresponding reference was the final in-hospital serum creatinine performed in case admissions without AKI episodes.

Results
The cohort was of mean age 53 (SD 25) years, of whom 29%, 12%, 12%, and 53% had diabetes, ischemic heart disease, cancers, and baseline eGFR <90 mL/min/1.73 m2, respectively. There were 911 AKI episodes in 869 patients. We derived and validated an algorithm in the testing dataset with an AUROC of 0.81 (0.78-0.85) for predicting AKI. At a 15% prediction threshold, our model generated 699 AKI alerts with 2 false positives for every true AKI and predicted 26% of AKIs. A lowered 5% prediction threshold improved the recall to 60% but generated 3746 AKI alerts with 6 false positives for every true AKI. Representative interpretation results produced by our model alluded to the top-ranked features that predicted AKI that could be categorized in association with sepsis, acute coronary syndrome, nephrotoxicity, or multiorgan injury, specific to every case at risk.

Conclusions
We generated an accurate algorithm from electronic health records through machine learning that predicted AKI by a lead time of at least 48 hours. The prediction threshold could be adjusted during deployment to optimize recall and minimize alert fatigue, while its precision could potentially be augmented by targeted AKI biomarker assessment in the high-risk cohort identified.
Instrumentos de Evaluación de las Influencias Socioculturales en la Interiorización de Ideales Corporales en Población Hispana
Authors: Vázquez Arévalo Rosalia 
Published: December 2021

El interés por la imagen corporal tiene cerca de cien años, ya en 1920, Mead (como se citó en Cash y Pruzinsky, 2002), mencionaba que ésta podría definirse como la “habilidad del cerebro para detectar peso, limitar forma y tamaño e incorporar éstos dentro de los esquemas mentales “(pág. 3). Dicho interés por la imagen corporal se acentuó en la década de 1970 cuando se observó que la interiorización de un modelo corporal predominante puede estar asociado a psicopatologías como la anorexia y bulimia nerviosas en las mujeres. En el caso de los varones la preocupación generalizada por el cuerpo o cierto tipo de figura es más reciente, hace 20 años aproximadamente; no obstante, también tiene consecuencias graves en algunos casos, como el desarrollo del trastorno dismórfico corporal.Bajo el concepto de influencias socio-culturales se estudia una serie de factores culturales y sociales que han promovido y validado valores estéticos como la delgadez para mujeres y la musculatura para varones, por lo que es importante la construcción de medidas o instrumentos que valoren este constructo, por ello, el objetivo de esta investigación fue describir y analizar la utilización de los dos cuestionarios más conocidos en la literatura que tienen como finalidad medir las influencias culturales en la asimilación de los modelos estéticos; el CIMEC y el SATAQ.
CURRENT ISSUES OF FORMATION AND IMPLEMENTATION OF THE TOURISM DEVELOPMENT PROGRAM IN CHERKASY REGION
Authors: Herman Iryna 
Published: December 2021

Peculiarities of formation of program tasks of tourism development in Cherkasy region are investigated. The analysis of indicators for compiling and determining the results of the implementation of tourism development programs in Ukraine for a number of years is carried out. The main directions of tourism development in current business conditions are highlighted. The topical issues of formation and implementation of the program of tourism development in Cherkasy region are determined taking into account the influence of a complex of factors, in particular those of economic, ecological, social character.
It is substantiated that in the basis of formation of program tasks for the purpose of assistance to the development of tourism in Cherkasy region it is necessary to consider strategic plans of development both of Ukraine as a whole, its regions, and features and priorities of separate administrative-territorial communities.
Emphasis is placed on the need to develop appropriate identifiers and indicators to characterize individual general indicators of tourism development in the respective territories, cluster units and to form a single base of potential and actual subject-object units of the tourism segment of the region's economy.
To this end, the article proposes a model for the formation of criteria for assessing the objectivity of the formation of strategic regional objectives in the field of tourism and the results of program tasks in the tourism segment of the region's economy.
The analysis of methodology of the formation of program tasks at the state level and criteria of taking into account obligatory indicators of an estimation of their performance on the basis of the achievement of corresponding qualitative and quantitative indicators both at the all-Ukrainian, and at regional level is carried out.
Proposals are made to improve the procedure taking into account the interests of local governments, administrative-territorial communities and professional public associations in the direction of improving adaptive program indicators for tourism development.