bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERK&nbsp;Inhibitor ASN007&nbsp;Effectively Overcomes Acquired Resistance to EGFR&nbsp;Inhibitor in Non-small Cell Lung Cancer
Authors: Ku Bo Mi , Heo Jae Yeong , Kim Jinchul , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju 
Published: February 2021

Abstract
The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Thus, development of effective strategies to overcome resistance to EGFR-TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR-TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR-TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR-TKIs synergistically decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR-TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR-TKIs by overcoming acquired resistance.
Optimal Timing for Primary Early Endoscopic Dacryocystorhinostomy in Acute Dacryocystitis
Authors: Sung Jae Yun , Kim Ju Mi , Hwang Jae yul , Kim Kyoung Nam , Kim Jae young , Lee Sung Bok 
Published: February 2021

Abstract

Purpose: To evaluate the surgical outcomes of primary early endoscopic dacryocystorhinostomy (EnDCR) in acute dacryocystitis (AD) and to determine the optimal timing for surgery.Methods: A retrospective review of the medical records was performed on consecutive patients who underwent primary early EnDCR (within 1 week) for AD between May 2010 and June 2020 (AD group) and age- and gender-matched control group of NLDO patients who underwent EnDCR (non-AD group). The primary outcome measures were surgical outcomes at the final follow-up examination. The secondary outcome measure was clinical course of AD patients. Subgroup analysis was performed to determine the optimal timing of surgery by comparing outcomes of very early EnDCR (within 3 days) and those of early EnDCR (between 4 and 7 days).Results: Forty-one patients were included in the AD group and 82 patients in the non-AD group. The anatomical and functional success rates were 87.8% and 82.9% in the AD group, and 91.5% and 84.1% in the non-AD group, which were not significantly different between the two groups (p = 0.532 and p = 0.863). In the AD group, the mean times for pain relief and resolution of swelling after surgery were 2.4 and 6.5 days after surgery. In subgroup analysis according to the timing of surgery, the time for symptom resolution after diagnosis, the length of hospital stay, and the duration of antibiotics treatment were significantly shorter after very early EnDCR (all ps < 0.05), whereas the surgical outcomes were not different between the 2 groups (p = 1.000)Conclusions: Primary early EnDCR is a safe and effective procedure for the treatment of AD. In particular, very early EnDCR, performed within 3 days, leads to faster recovery and shortens the course of antibiotic treatment.
Continuous Renal Replacement Therapy in COVID-19-associated AKI: Adding Heparin to Citrate to Extend Filter Life – a Retrospective Cohort
Authors: Valle Eduardo de Oliveira , Cabrera Carla Paulina Sandoval , de Albuquerque Claudia Coimbra César , Silva Giovanio Vieira da , de Oliveira Márcia Fernanda Arantes , Sales Gabriel Teixeira Montezuma , Smolentzov Igor , Reichert Bernardo Vergara , Andrade Lucia , Seabra Victor Faria , Lins Paulo Ricardo Gessolo , Rodrigues Camila Eleuterio 
Published: February 2021

Abstract
Background: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk.Methods: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV+ AKI and COV− AKI, respectively), submitted to CRRT. Filter clotting risks in the first 72 hours were compared between groups.Results: Between January 2019 and July 2020, 248 patients were evaluated: 189 in the COV+ AKI group and 59 in the COV− AKI group. Filter clotting occurred during the first 72 hours of CRRT in 96 patients (38.7%). Heparin use conferred protection against filter clotting, resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV+ AKI patients than among the COV− AKI patients, although it was similar between the COV+ AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (6086 ng/ml). In the multivariate analysis, the protective effect of heparin against filter clotting persisted, whereas an elevated D-dimer level, high platelet count, and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was not a risk factor for filter clotting.Conclusions: In COV+ AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with low risk of complications.
Data-Driven Real-Time Prediction for Interfacial Fluid Mechanics: Droplet Evaporation
Authors: Andalib Sahar , Taira Kunihiko , Kavehpour H. Pirouz 
Published: February 2021

Abstract
Droplet evaporation plays crucial roles in biodiagnostics, microfabrication, and inkjet printing. Experimentally studying the evolution of a sessile droplet consisting of two or more components needs sophisticated equipment to control the vast parameter space affecting the physical process. On the other hand, non-axisymmetric nature of the problem, attributed to compositional perturbations, introduces challenges to numerical methods. In this work, droplet evaporation problem is studied from a new perspective. We analyze evolution of a sessile methanol droplet through data-driven classification and regression techniques. The models are trained using experimental data of methanol droplet evolution under various environmental humidity levels and substrate temperatures. At higher humidity levels, the interfacial tension and subsequently contact angle increase due to higher water uptake into droplet. Therefore, different regimes of evolution are observed due to adsorption-absorption and possibly condensation of water which turns the droplet into a binary system. We use classification algorithms to predict the regime of droplet with point-by-point analysis of droplet profile. Decision tree demonstrates a better performance compared to Na\text{\"i}ve Bayes (NB) classifier. Furthermore, through utilizing regression techniques, we predict the humidity level surrounding droplet as well as time evolution of macroscopic parameter (diameter or contact angle) of droplet. The prediction results show promising performance for four cases of methanol droplet evolution under conditions that are unseen by the model which demonstrates the capability of the model to capture the complex physics underlying binary droplet evolution.
Migrânea: revisão de literatura
Authors: Cruz Marina Coimbra da , Camargo Renan Paes de , Cruz Lucas Coimbra da , Schiefelbein Nadiane , Cruz Daniela Moreira da , Cruz Marlene Cabral Coimbra da 
Published: February 2021

Introdução: Cefaleia representa um problema de saúde pública, podendo ser primárias, quando são por si só a patologia ou secundárias quando são apenas um sintoma de uma outra patologia de base. Objetivos: Revisar as características e pontos principais da migrânea. Materiais e Métodos: revisão narrativa realizada em bases de dados digitais, livros e informações de organizações de referência mundial. Resultados: A migrânea é um tipo de cefaleia primária de alta prevalência, sendo mais comum em mulheres. Pode ser com ou sem aura – sintomas neurológicos focais que precedem a dor – ou crônica. Caracteriza-se por cefaleia pulsátil, unilateral, de intensidade de moderada a grave, associada a náusea, vomito, foto ou fonofobia e que se agrava com atividades físicas rotineiras. Deve ser diferenciada de outras cefaleias primarias e, quando na presença de sinais de alarme, também das secundárias, em especial se na terceira idade. Fatores como odores e luzes fortes, consumo de bebida alcoólica, certos alimentos, jejum prolongado, distúrbios do sono e ciclo menstrual podem desencadear uma crise. Seu tratamento pode ser farmacológico ou não, além de envolver medidas gerais; e pode ser sintomático ou profilático – mais indicado em casos mais graves ou refratários. Dentre os medicamentos utilizados durante as crises há os específicos (triptanos e derivados da ergotamina) e não específicos (analgésicos e anti-inflamatórios não esteroidais). Conclusão: Conclui-se que a migrânea deve ser reconhecida e diagnosticada correta e precocemente, objetivando uma terapêutica adequada e individualizada para que se alcance uma melhora na qualidade de vida do paciente.
The potential of ensemble WT-EEMD-kernel extreme learning machine techniques for prediction suspended sediment concentration in successive points of a river
Authors: Roushangar Kiyoumars , Aghajani Nasrin , Ghasempour Roghayeh , Alizadeh Farhad 
Published: February 2021

Abstract
Sediment transport is one of the most important issues in river engineering. In this study, the capability of the Kernel Extreme Learning Machine (KELM) approach for predicting the river daily Suspended Sediment Concentration (SSC) and Discharge (SSD) was assessed. Three successive hydrometric stations of Mississippi river were considered and based on the sediment and flow characteristics during the period of 2005–2008. Several models were developed and tested for SSC and SSD modeling. For improving the applied model efficiency, two post-processing techniques, namely Wavelet Transform (WT) and Ensemble Empirical Mode Decomposition (EEMD), were used. Also, two states of modeling based on stations' own data (state 1) and previous stations' data (state 2) were considered. The single and integrated KELM model results comparison indicated that the integrated WT and EEMD-KELM models resulted in more accurate outcomes. Results showed that data processing with WT was more effective than EEMD in increasing the models' efficiency. Data processing enhanced the models' capability by up to 15%. The results showed that the state 1 modeling led to better results, however, using the integrated KELM approaches the previous stations data could be applied successfully for SSC and SSD modeling when the stations' own data were not available.
HIGHLIGHT
The suspended sediment concentration (SSC) and suspended sediment discharge (SSD) were predicted via artificial intelligence approach in successive hydrometric stations. The data pre-processing impacts on models' efficiency improvement was assessed. The sensitivity analysis showed the most effective subseries was obtained from pre-processing models.
Effectiveness of solar disinfection for household water treatment: an experimental and modeling study
Authors: Karim Md. Rezaul , Khan Md. Habibur Rahman Bejoy , Akash Md. Abu-Sa-Ad , Shams Shahriar 
Published: February 2021

Abstract
Solar disinfection (SODIS) is a simple and low-cost household water treatment (HWT) option used for disinfection of drinking water. In this study, the bacterial inactivation potential of SODIS was evaluated under the solar irradiance observed in different seasons in Bangladesh according to WHO evaluation protocol of HWT, and the SODIS experiments were conducted for both transmissive and reflective reactors using PET bottles and plastic bags. In summer, log reduction value (LRV) more than 5 was observed for the transmissive PET reactors for 6 to 8 hr exposure to sunlight and the treated water complied with the microbial standard of zero colony forming units/100 mL in drinking water. In monsoon and winter, LRV &gt; 4 can be achieved for 16 hr and 8 hr exposure to sunlight, respectively, using reflective reactors. The plastic bag was found to be more effective than PET. A safe exposure time was estimated from the Weibull model to be maintained for SODIS application to achieve 4.0 LRV and also to prevent the re-growth of microorganisms in the treated water. A significant re-growth of microorganisms was observed in the treated water, thus SODIS with other HWT processes can be recommended for use in communities with an unsafe drinking water supply.
Detection of potentially pathogenic free-living amoebae from the Caspian Sea and hospital ward dust of teaching hospitals in Guilan, Iran
Authors: Mahmoudi Mohammad Reza , Zebardast Nozhat , Masangkay Frederick R. , Karanis Panagiotis 
Published: February 2021

Abstract
Free-living amoebae (FLA) thrive in diverse environmental conditions. The present study aimed to define the FLA distribution from the Caspian Sea as well as from hospital ward dust from Guilan, Iran. Seawater (20) and hospital ward dust samples (100) were collected from May to June 2018. Seawater samples were vacuum filtered through a 0.45 μm pore-size membrane. Dust was collected using sterile gauze, washed with sterile distilled water, with washings collected thereafter. Washings were similarly filtered as seawater samples. FLA from the filtered material was cultivated in non-nutrient agar. Molecular analysis was performed by PCR and sequencing using specific primers for Acanthamoeba, Naegleria, and Vermamoeba/Hartmanella. Culture and PCR returned 50 and 65% positivity, respectively, for seawater samples where sequencing revealed Acanthamoeba T2, T5 and T6 genotypes and A. palestinensis and A. lenticulata, as well as N. dobsoni and N. clarki. In addition, 30% amoebic growth and 16% PCR detection were observed from hospital ward dust samples where sequencing revealed Acanthamoeba T2, T4 and T11 genotypes and A. castellanii, A. palestinensis and A. stevensoni as well as N. clarki. For both seawater and dust samples, Acanthamoeba was the dominant isolate. The detection of potentially pathogenic FLA from seawater may pose a threat to the public, while the presence of the same in dust spells threats to both hospital staff and patients, in particular, immunocompromised individuals. Public education, awareness, improved sanitation and hygiene, and the crafting of diagnostic strategies for the early detection of FLA in humans are necessary for the mitigation and management of potential human infection cases.
Design and Evaluation of Sustained Release of Ornidazole by Dental Inserts
Authors: Harika Sunchu , Kumar Y. Shravan , Rao Y. Madhusudhan , Sriram Pavani , Shankar Uma 
Published: February 2021

Aim & Background:
Ornidazole is an antimicrobial drug used to treat certain types of vaginal, urinary
tract, and interstitial infections. The study aims to formulate and evaluate the dental inserts by using a drug candidate
to sustained drug release to improve patient compliance, reduce dosing frequency, reduce the risk of dose dumping,
and avoid the first-pass metabolism. They have better therapeutic efficacy and fewer side effects.

Methods:
The dental inserts were prepared using various polymers alone and in combination with the different ratios
of polymers. The evaluation parameters like thickness, drug content, content uniformity, moisture reuptake, weight
variation, swelling studies, and erosion studies of the optimized inserts were studied. The in-vivo studies were conducted
to determine the reduction of pocket depth in human volunteers.

Results:
The system containing ethylcellulose and hydroxyl methyl propyl cellulose K100M (4:1) formulation F6
was optimized because drug release was sustained up to 120 hrs concerning other formulations. Optimized formulation
followed first-order kinetics and Peppas release kinetics via fickian diffusion. There was no swelling, itching,
irritation, and no reduction in the pocket depth in in-vivo studies.

Conclusion:
The study concluded that dental inserts could extend the release of Ornidazole for many hours and also
enhance bioavailability. Furthermore, they also help in avoiding the first-pass effect. In vivo studies’ observations
showed no itching, irritation, swelling, and pocket-depth reduction.
Solvent Bar Microextraction Combined with HPLC-DAD for Simultaneous
Determination of Diuretics in Human Urine and Plasma Samples
Authors: AL-Hashimi Nabil N. , El-Sheikh Amjad H. , Alruwad Manal I. , Odeh Mohanad M. 
Published: February 2021

Background:
A simple and powerful microextraction procedure, the solvent bar microextraction
(SBME), was used for the simultaneous determination of two diuretics, furosemide and spironolactone
in human urine and plasma samples, using high-performance liquid chromatography
coupled with diode array detection (HPLC-DAD).

Methods:
The appropriate amount (2 μL) of 1-octanol as an organic solvent confined within 2.5 cm
of a porous hollow fiber micro-tube, sealed at both ends was used for this procedure. The conditions
for the SBME were optimized in water and the analytical performance was examined in spiked human
urine and plasma samples.

Results:
The optimized method exhibited good linearity (R2> 0.997) over the studied range of higher
than 33 to 104μg L-1 for furosemide and spironolactone in urine and plasma samples, illustrating a
satisfactory precision level with RSD values between 2.1% and 9.1%.

Discussion:
The values of the limits of detection were found to be in the range of 6.39 to 9.67μg L-1,
and extraction recovery ˃ 58.8% for both diuretics in urine and plasma samples. The applicability and
effectiveness of the proposed method for the determination of furosemide and spironolactone in patient
urine samples were tested.

Conclusion:
In comparison with reference methods, the attained results demonstrated that SBME
combined with HPLC-DAD was proved to be simple, inexpensive, and promising analytical technology
for the simultaneous determination of furosemide and spironolactone in urine and plasma samples.
Simple and Environment-Friendly Method for Graphene Synthesis by
Using Ultrasound
Authors: Markovska Irena , Georgiev Dimitar , Yovkova Fila , Abrashev Miroslav 
Published: February 2021

Background:
This paper proposes a technology for the production of monolayer graphene
by an easy, acscessible, and non-toxic method.

Methods:
For the preparation of graphene, a combination of chemical and physical (ultrasonic)
treatment of the original graphite precursor (purity >99%) was applied.
The precursor of graphite is placed in a beaker with a solution of KOH or H2SO4. The mixtures were
homogenized well and sonicated for 4h. The applied ultrasound has a power of 120 W, frequency 40
kHz. Due to the effects of ultrasound, complex processes take place in the solutions, which leads to the
formation of superfine graphene. Better results were obtained at samples treated with 2n H2SO4.
The physicochemical properties of the resulting graphene were characterized mainly by Raman spectroscopy,
FT-IR, TEM, SEM, and electrical conductivity measurements.

Results:
Our research was focused mainly on the field of nanotechnology, in particular on the synthesis
of graphene, which could be used as a coating on electrodes for supercapacitors. In this connection,
three series of samples were developed in which the pristine graphite was treated with 2n
H2SO4, 4n H2SO4, and 6n H2SO4, respectively, and their electrical properties were measured.

Conclusion:
The obtained graphene shows electrical resistivity 2-3 times lower than that of the precursor
of pure graphite.
Cannabis Sativa L. Flower and Bud Extracts Inhibited In vitro Cholinesterases
and β-Secretase Enzymes Activities: Possible Mechanisms of
Cannabis Use in Alzheimer Disease
Authors: Mooko Teboho , Bala Asis , Tripathy Satyajit , Kumar Chethan S. , Mahadevappa Chandrashekara P. , Chaudhary Sushil K. , Matsabisa Motlalepula G. 
Published: February 2021

Background:
There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer’s disease, but there is lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer’s disease.

Aim:
The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and β-secretase enzyme activity as one of the possible mechanisms of Alzheimer’s disease.

Methods:
The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and β-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts.

Results:
Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards β-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure.

Conclusion:
Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.
Assessment of Quantum Scaling Length Model for Cylindrical Surrounding Double-Gate (CSDG) MOSFET
Authors: Maduagwu Uchechukwu A. , Srivastava Viranjay M. 
Published: February 2021

Aim:
The aim of this study is the derivation and assessment of quantum scaling length of
Cylindrical Surrounding Double-Gate (CSDG) MOSFET with respect to Silicon body thickness.

Objectives:
To derive the quantum natural length of CSDG MOSFET with respect of Silicon body
Thickness, observe the behaviour of the CSDG MOSFET at the nanoscale regime and compare the behaviour
of the CSDG MOSFET with Cylindrical Surrounding Gate (CSG) MOSFET.

Methods:
The authors employed the mathematical analysis. The quantum energy level is analysed using
Schrodinger equation by assuming one-dimensional approach and a negligible potential well.

Results:
The analytical results obtained from classical and quantum natural length are compared with
the numerical simulations. Also, the model was compared with CSG MOSFET. Results show that proposed
analytical close-form expression that approximately matches the numerical simulation, and the
proposed CSDG MOSFET will be better than CSG MOSFET at quantum level even though it has
smaller quantum natural length than CSG MOSFET.

Conclusion:
In this research work, quantum scaling length model and quantum scaling factor have been
proposed using the quantum confinement approach. The performance assessment of the CSDG
MOSFETs provided an opportunity of determining the scaling limit of CSDG MOSFETs by evaluating
the trade-off between the quantum natural length and the classical natural length of CSDG MOSFETs.
Results obtained were compared with CSG MOSFETs to show that CSDG MOSFETs offer better device
characteristics.