bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating two GIS-based semi-distributed hydrological models in the Bhagirathi-Alkhnanda River catchment in India
Authors: Kumar Dilip , Bhattacharjya Rajib Kumar 
Published: October 2020

Abstract
The hydrological models are used for simulating the runoff of a river basin based on available rainfall data and other parameters. Over the years, several hydrological models have been developed in different parts of the world. Two such semi-distributed hydrologic models are SWAT and HEC-HMS. In this study, a comparative analysis has been carried out to evaluate the performance of these two distributed hydrological models as a flood forecasting tool. The Alkhnanda and Bhagirathi rivers, which flow into the Tehri Reservoir, Uttarakhand and pass through Tehri, Uttarkashi and Chamoli districts of Uttarakhand, India, are selected for the analysis. The performance of these two models is evaluated by using standard statistical methods. The comparative analysis of these two models shows that the SWAT model is performing slightly better in comparison to the HEC-HMS model, especially in the lean period. The underestimation of peak discharge may be due to the contribution of significant snowmelt discharge during the rainy season. The models are also used to predict future discharge under different climate change scenarios. The future prediction shows that the peak discharge of Alkhnanda may be increased by 27 and 47% under RCP4.5 and RCP8.5, respectively.
Removal of sulfamethizole from aqueous solution using advanced oxidation processes: effects of pH and salinity
Authors: Wang A. M. , Wu C. H. , Huang E. H. 
Published: October 2020

Abstract
This study investigates the removal of sulfamethizole (SFZ) in ozone (O3), O3/Na2S2O8 (sodium persulfate), UV/Na2S2O8, UV/O3, and UV/O3/Na2S2O8 systems. The effects of pH and salinity on SFZ mineralization were evaluated. The mineralization of SFZ followed pseudo-first-order kinetics. At pH 5, the rate constants of SFZ mineralization in O3, O3/Na2S2O8, UV/Na2S2O8, UV/O3, and UV/O3/Na2S2O8 systems were 0.576, 0.924, 0.702, 1.26, and 5.21 h−1, respectively. The SFZ mineralization rate followed the order pH 5 &gt; pH 7 &gt; pH 9 in all tested advanced oxidation processes. Salinity increased the rate of SFZ mineralization in O3 and O3/Na2S2O8 systems and decelerated it in UV/Na2S2O8, UV/O3, and UV/O3/Na2S2O8 systems. UV/O3/Na2S2O8 was the best system for mineralizing SFZ, and sulfate radicals were the predominant species in UV/O3/Na2S2O8.
Chalcones Acting as Inhibitors of Cholinesterases, β-Secretase and β- Amyloid Aggregation and other Targets for Alzheimer’s Disease: A Critical Review
Authors: Antoniolli Giorgio , Almeida Wanda P. , Frias Camila C. , de Oliveira Tiago B. 
Published: October 2020

Background:
Alzheimer's disease (AD) involves an irreversible and progressive
neurodegeneration, with multifactorial pathophysiology, including the cholinergic
deficit, amyloid plaques, neurofibrillary tangles, oxidative stress, and neurodegeneration.
Despite the severity of the disease, the therapeutic arsenal is limited, arousing the interest
of researchers to search for substances that can act on these markers.

Objective:
In this review, we highlight some relevant points: the ability of chalcones to act on different targets related to the
pathophysiology of Alzheimer's disease: cholinesterases, amyloid peptide, beta-secretase and other biomarkers.

Method:
This mini-review covered the literature concerning chalcones bioactivity from 2010 until now. In addition to the
theoretical review, we included the prediction of physicochemical properties, using SwissADME software.

Results:
We found that the majority of the chalcones have been tested against cholinesterases, with moderate to good potencies, but in recent years, the number of publications related to targets of the amyloid hypothesis has been growing. Regarding the physicochemical properties, chalcones have a good profile, except the water solubility, which is not favorable.

Conclusion:
The most important characteristic of these molecules,is the given that many of the examples mentioned here
act on more than one target, characterizing them as multi-target compounds. Regarding predicted properties, solubility
stands out as the most problematic one, however these structures can incorporate functional groups that circumvent this
problem of solubility without interfering in the biological activity.
Improving Cytotoxicity against Breast Cancer Cells by Using Mixed-Ligand Ruthenium(II) Complexes of 2,2'-Bipyridine, Amino Acid, and Nitric Oxide Derivatives as Potential Anticancer Agents
Authors: Gaspari Ana P.S. , da Silva Roberto Santana , Carneiro Zumira A. , de Carvalho Marcelo Rodrigues , Carvalho Ivone , Pernomian Laena , Ferreira Lucimara P. , Ramos Loyanne C.B. , de Souza Gabriel Aguiar , Formiga André L.B. 
Published: October 2020

Background:
Several metal-based molecules that display cytotoxicity against multiple cell lines have
been pursued in an attempt to fight against cancer and to overcome the typical side effects of drugs like cisplatin.
In this scenario, ruthenium complexes have been extensively studied due to their activity in both in vitro and in
vivo biological systems, including various cancer cell strains.

Objective:
We aimed to develop a method to synthesize novel [Ru(NO)(bpy)2L2]2+ complexes containing amino
acid ligands by using an alternative Click Chemistry approach, namely the copper azide-alkyne cycloaddition
reaction (CuAAC reaction), to construct nitrosyl/nitrite complexes bearing a modified lysine residue.

Methods:
We synthesized a new ligand by Click Chemistry approach and new compounds bearing the
unprecedented ligand. Cytotoxicity was assessed by the classical MTT colorimetric assay. MCF-7 and MDAMB-
231 cells were used as breast cancer cell models. MCF-10 was used as a model of healthy cells.

Results:
Amino acid ligands related to N3-Lys(Fmoc) and the new pyLys were successfully synthesized by the
diazotransfer reaction and the CuAAC reaction, respectively. The latter reaction involves coupling between
N3-Lys(Fmoc) and 3ethynylpyridine. Both N3-Lys(Fmoc) and the new pyLys were introduced into the ruthenium
bipyridine complex I, or cis-[RuII(NO)(NO2)(bpy)2]2+, to generate the common nitro-based complex III, which
was further converted to the final complex IV. Results of the MTT assay proved the cytotoxic effect of cis-
[RuII(NO)(pyLysO-)(bpy)2](PF6)2 against the mammalian breast cancer cells MCF-7 and MDA-MB231.

Conclusion:
The viability assays revealed that complex IV, bearing a NO group and a modified lysine residue,
was able to release NO and cross tumor cell membranes. In this work, Complex IV was observed to be the most
active ruthenium bipyridine complex against the mammalian breast cancer cells MCF-7 and MDA-MB231: it
was approximately twice as active as cisplatin, whilst complexes I-III proved to be less cytotoxic than complex
IV. Additional tests using healthy MCF 10A cells showed that complexes II-IV were three- to sixfold less toxic
than cisplatin, which suggested that complex IV was selective against cancer cells.
The Pattern of Calculated Inflammation Ratios as Prognostic Values in Patients with Colorectal Cancer
Authors: Ciocan Andra , Bolboacă Sorana D. , Drugan Cristina , Ciocan Răzvan A. , Graur Florin , AL Hajjar Nadim 
Published: October 2020

Aim:
In our study, we evaluated the prognostic value of four calculated inflammatory ratios in patients with colorectal cancer.

Material and methods:
A six-year retrospective study was conducted on subjects admitted for
colorectal cancer at "Prof. Dr. Octavian Fodor" Regional Institute of Gastroenterology and
Hepatology Cluj-Napoca, Romania, from January 2014 until September 2019. The medical charts
of patients diagnosed with colorectal cancer were used as the source of raw data and for the
calculation of four ratios (neutrophil-to-lymphocyte ratio-NLR, derived neutrophil-to-lymphocyte
ratio-dNLR, platelet-to-lymphocyte ratio-PLR, and systemic immune-inflammation index-SII),
considered as prognostic markers related to mortality in colorectal cancer.

Results:
One thousand six hundred and eighty-eight patients, with ages ranging from 17 to 98 years,
were evaluated. NLR and dNLR displayed significantly higher values among patients who died
(NLR: 4.2 for deceased vs. 3.4 for alive, P-value=0.0224; dNLR: 2.7 for deceased vs. 2.3 for alive, Pvalue=
0.0566). Ischemic cardiomyopathy (odds ratio (OR)=2.70), liver cirrhosis (OR=7.84), postoperative
complications (OR=2.39), and neutrophil-to-lymphocyte ratio (OR=1.08) proved to be
significant prognostic factors for the primary outcome, independent of age and gender.

Conclusions:
Patients with high NLR, postoperative complications, ischemic cardiomyopathy an
d/or liver cirrhosis are the
candidates to a less favorable outcome among subjects with colorectal cancer regardless the age and gender.
Prognostic Significance of Hematopoietic-cell Serglycin for the Survival of Hepatocellular Carcinoma: A Single-center Retrospective Study
Authors: Li Yue , Chen Hongjie , Lu Huiqiong , Zou Zengcheng , Li Yongwei 
Published: October 2020

Aim and Objective:
Inflammation-related changes in peripheral blood cells and blood proteins are prognostic factors for survival in hepatocellular carcinoma (HCC), but their usefulness is limited by active bacterial infection. This study
investigated whether infection interfered with the predictive value of serglycin, a proteoglycan found in hematopoietic cells,
on survival in HCC.

Materials and Methods:
Patients with hepatitis B virus (HBV)-induced HCC, 100 without and 30 with bacterial infection,
and 30 healthy adult controls were enrolled retrospectively. Baseline clinical data collected before treatment with transarterial chemoembolization (TACE) was evaluated and serglycin expression was assayed by flow cytometry. Receiver operating
characteristic (ROC) curve analysis identified serglycin cutoff values for patient stratification. Cox regression and Kaplan–
Meier analyses were performed to identify predictors of overall survival (OS).

Results:
Serglycin levels in peripheral blood cells were higher in both groups of HCC patients than in the control group.
Cholinesterase, lung metastasis, average neutrophil serglycin fluorescence intensity, and aspartate aminotransferase levels
were associated with survival risk. Barcelona Clinic Liver Cancer stage A was associated a good prognosis of OS.

Conclusion:
The intensity of serglycin fluorescence in peripheral neutrophils was independently predictive of survival in
HCC and its value was not limited by bacterial infection. The method presented here is a simple and feasible way to predict
prognosis in HCC patients with TACE.
Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology
Authors: Vieira Cristina , Nery Lucas , Martins Ludimila , Jabour Luiz , Dias Raphael , Simões e Silva Ana Cristina 
Published: October 2020

Background::
The Coronavirus Disease 2019 (COVID-19) is becoming the major health
issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research
and old experience with other coronaviruses highlighted a probable underlying mechanism
of disturbance of the renin-angiotensin system (RAS) that is associated with the intrinsic effects of
SARS-CoV-2 infection.

Objective::
In this review, we aimed to describe the intimate connections between the RAS components,
the immune system and COVID-19 pathophysiology.

Methods::
This non-systematic review article summarizes recent evidence on the relationship between
COVID-19 and the RAS.

Results::
Several studies have indicated that the downregulation of membrane-bound ACE2 may exert
a key role for the impairment of immune functions and for COVID-19 patients’ outcomes. The
downregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced
by the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating
more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor
with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune
system, which leads to a reduction of ACE2 receptor expression.

Conclusion::
Recent research provides evidence of a reduction of the components of the alternative
RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II
can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis
and angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions
of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.
Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues
Authors: Ahsan Mohamed Jawed , Saini Deepak , Sharma Piush , Jadav Surender Singh , Bakht Mohammad Afroz , Salahuddin  , Alluri Ramesh , Faiyazuddin Md 
Published: October 2020

Cancer is one of the leading causes of death. The aim of the present study was to synthesize
and investigate the anticancer and antioxidant activities of some 3,5-bis(substituted benzylidene)-
1-ethylpiperidin-4-one analogues (4a-g).

The 3,5-bis(substituted benzylidene)-1-ethylpiperidin-4-one analogues (4a-g) were prepared from
the precursor, piperidin-4-one hydrochloride (1). The initial step involved the synthesis of intermediates,
3,5-bis(substituted benzylidene)piperidin-4-one analogues (3a-g) followed by their ethylation
with C2H5I in acetone and K2CO3 to obtain the title compounds (4a-g). The Fourier transform
infrared (FTIR), nuclear magnetic resonance (1H & 13C NMR), mass spectrometry and microanalysis
were used to characterize the title compounds (4a-g). All the compounds were further
evaluated for their anticancer activity by SRB assay and NCI US protocol, while the antioxidant
activity was evaluated by DPPH free radical assay. All the title compounds (4a-g) were subjected
to molecular docking studies against EGRF tyrosine kinase, a potential target for anticancer agents,
to study the possible mode of interaction of our compounds with the molecular target.

:
The compound 4g showed significant anticancer activity with GI50 of 28.2 μM against MCF-7
(Breast cancer cell line). The antioxidant activity of compound 4g (IC50 = 14.98±0.91 μM) was
found to be comparable to the standard drug ascorbic acid. The binding modes of compounds 4a-g
against the molecular target EGFR tyrosine kinase were also studied. The structure-activity relationship
(SAR) was also studied.

:
The compound 4g showed significant anticancer activity with GI50 of 28.2 μM against MCF-7
(Breast cancer cell line). The antioxidant activity of the compound, 4g was found to be comparable
to the standard drug ascorbic acid, while its anticancer activity was found to be less than that of the
standard drug adriamycin.
In Vitro Characterization of a Novel Consensus Bacterial 6-Phytase and One of its Variants
Authors: Christensen Trine , Dersjant-Li Yueming , Sewalt Vincent , Mejldal Rie , Haaning Svend , Pricelius Sina , Nikolaev Igor , Sorg Robin A. , de Kreij Arno 
Published: October 2020

Background::
Microbial phytases are added to animal feed to hydrolyze phytic acid (myoinositol
hexakisphosphate, IP6) and phytate (salt of phytic acid) increasing phosphorus bioavailability.
Novel phytases with enhanced bio-efficacy are being developed.

Objective::
To characterize the biochemical and enzymatic properties of a novel consensus bacterial 6-
phytase and its variant (PhyG), produced in Trichoderma reesei.

Methods::
The in vitro specific activity, kinetic parameters, pH-activity profiles (relative to pH5.5), IP6
degradation, hydrolysis products and phosphate release of the phytases were determined using sodium
phytate substrate. Melting point (Tm) was determined by differential scanning calorimetry and thermostability
assessed by measuring residual activity at different temperatures. In vivo effects of PhyG
supplementation at 0 to 1,000 FTU/kg on ileal IP6 digestibility and IP ester concentrations were determined
in piglets.

Results::
Both phytases exhibited pH optima of 3.5-4.5, high relative activity over a wide pH range
(pH2.0-5.0), and substantial relative activity at pH1.5. At pH3.0, the specific activity of the PhyG variant
was 1487 U/mg protein and at pH3.5 the kinetic constants were 240 μM (Km) and 1873 s-1 (Kcat).
The hydrolysis of IP6 by both phytases was rapid. The major initial hydrolysis product was DLI(
1,2,3,4,5)P5, designating the phytases as bacterial 6-phytases (EC 3.1.3.26). Hydrolysis occurred at
the D-3 (L-1) position in ~30% of instances, indicating a dual-specificity.

Conclusion:
Both phytases showed high thermostability compared to wild type and existing commercial
bacterial 6-phytases; PhyG exhibited 95% residual activity after 20 min incubation at 85.4ºC
(pH5.5), Tm50 of ~93.2ºC and Tm of 98.8ºC. In vivo, PhyG at 1,000 FTU/kg achieved an ileal digestibility
of IP6 of 89.3%.
Pengembangan modul online untuk meningkatkan hasil belajar Ilmu Pengetahuan Sosial (IPS)
Authors: Arriany Ike , Ibrahim Nurdin , Sukardjo Mochammad 
Published: October 2020

Tujuan dari penelitian ini adalah mengembangkan modul online yang efektif untuk meningkatkan ketuntasan hasil belajar Ilmu Pengetahuan Sosial (IPS) di SMP. Modul online ini dikembangkan untuk membantu siswa Sekolah Menengah Pertama (SMP) dalam mencapai standar kompetensi yang ditetapkan pada mata pelajaran IPS. Metode penelitian yang digunakan adalah metode penelitian dan pengembangan. Model yang digunakan untuk mengembangkan modul online untuk meningkatkan hasil belajar IPS adalah model Rowntree dan web based design. Data pada penelitian dan pengembangan ini dikumpulkan berdasarkan quesioner, interview, dokumen hasil belajar, dan test. Hasil uji validasi ahli materi, media, desain instruktional dan uji satu-satu menunjukkan bahwa modul online masuk dalam kategori sangat baik dan layak digunakan dalam pembelajaran IPS. Hasil uji keterbacaan dengan menggunakan fog-index juga menunjukkan teks pada modul online pembelajaran IPS mudah untuk dipahami. Hasil uji lapangan dengan menggunakan perhitungan t-test menunjukkan terdapat perbedaan signifikan terhadap hasil belajar siswa sebelum dan sesudah menggunakan modul dengan kata lain modul online untuk pembelajaran IPS dinilai efektif dan dapat meningkatkan ketuntasan hasil belajar siswa. AbstractThe purpose of this research is to develop an effective online learning module to enhance student learning results. The development of the module aims at assisting junior high school students to achieve expected competencies in social studies. This research applies Research and Development method. Rowntree and web-based design models are used to develop online modules. All data are collected by document study, questionnaires, tests, and interviews. Based on the expert matter, media expert, instructional design expert, and face to face tryouts, the validity evaluation shows that the online module is appropriate and feasible to use in learning. Moreover, readability judgment using a fog-index score shows that the text is easy to understand. The result of the field trials using the t-test equation shows that there is a significant increase in students’ learning results before and after using the module. In conclusion, online module learning is effective to improve students’ learning results in order to achieve expected competencies.
Towards The Automated, Empirical Filtering of Drug-Drug Interaction Alerts in Clinical Decision Support Systems: Historical Cohort Study of Vitamin K Antagonists
Authors: Chazard Emmanuel , Boudry Augustin , Beeler Patrick Emanuel , Dalleur Olivia , Hubert Hervé , Tréhou Eric , Beuscart Jean-Baptiste , Bates David Westfall 
Published: October 2020

Background
Drug-drug interactions (DDIs) involving vitamin K antagonists (VKAs) constitute an important cause of in-hospital morbidity and mortality. However, the list of potential DDIs is long; the implementation of all these interactions in a clinical decision support system (CDSS) results in over-alerting and alert fatigue, limiting the benefits provided by the CDSS.

Objective
To estimate the probability of occurrence of international normalized ratio (INR) changes for each DDI rule, via the reuse of electronic health records.

Methods
An 8-year, exhaustive, population-based, historical cohort study including a French community hospital, a group of Danish community hospitals, and a Bulgarian hospital. The study database included 156,893 stays. After filtering against two criteria (at least one VKA administration and at least one INR laboratory result), the final analysis covered 4047 stays. Exposure to any of the 145 drugs known to interact with VKA was tracked and analyzed if at least 3 patients were concerned. The main outcomes are VKA potentiation (defined as an INR≥5) and VKA inhibition (defined as an INR≤1.5). Groups were compared using the Fisher exact test and logistic regression, and the results were expressed as an odds ratio (95% confidence limits).

Results
The drugs known to interact with VKAs either did not have a statistically significant association regarding the outcome (47 drug administrations and 14 discontinuations) or were associated with significant reduction in risk of its occurrence (odds ratio<1 for 18 administrations and 21 discontinuations).

Conclusions
The probabilities of outcomes obtained were not those expected on the basis of our current body of pharmacological knowledge. The results do not cast doubt on our current pharmacological knowledge per se but do challenge the commonly accepted idea whereby this knowledge alone should be used to define when a DDI alert should be displayed. Real-life probabilities should also be considered during the filtration of DDI alerts by CDSSs, as proposed in SPC-CDSS (statistically prioritized and contextualized CDSS). However, these probabilities may differ from one hospital to another and so should probably be calculated locally.