bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE ROLE OF EPITHELIAL-TO-MESENCHYMAL TRANSITION AND AUTOPHAGY IN ANTITUMORAL RESPONSE OF MELANOMA CELL LINES TO TARGET INHIBITION OF MEK AND mTOR KINASES
Authors: Ryabaya O. O. , Prokofieva A. A. , Khochenkov D. A. , Akasov R. A. , Burov S. V. , Markvicheva E. A. , Stepanova E. V. 
Published: July 2019

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by downregulatoin of the EMT.Objective: to study the effect of MEK and mTOR co-inhibition on cell viability, ability to form 3D-spheroids and migratory capacity of melanoma cell lines, and correlation of these changes with EMTand autophagy-related markers.Material and Methods. Melanoma cell lines Mel Z and Mel MTP were derived from patients, who were treated at the N.N. Blokhin National Medical Research Center of Oncology. The antiproliferative effect of binimetinib and/or rapamycin was studied by the MTT -test. 3D spheroids were formed using RGD peptides. Cell migration and invasion were assessed by a Boyden chamber migration assay. The expression levels of autophagy and EMT markers were investigated by immunocytochemistry or immunoblotting.Results. Rapamycin increased cytotoxicity of binimetinib in both 2D and 3D melanoma cell line cultures. At the same time, binimetinib and rapamycin reduced invasion, but not migration capacity of melanoma cells in vitro. The effectiveness of the combination was associated with a decrease in the EMT markers (N-cadherin and β-catenin) and autophagy markers (Beclin 1, p62/SQST M1 and LC3BII ) in melanoma cells.Conclusion. Inactivation of autophagy and EMT leads to overcoming the resistance to current anti-melanoma therapy and can be considered as a promising target for the treatment of melanoma.
Discussion on stability analysis and support technology of surrounding rock of gob-side entry retaining
Authors: Zheng Wenxiang , Duan Huiqiang 
Published: July 2019

In order to further analyze the stability and control mechanism of surrounding rock in the gob-side entry retaining, the slip instability coefficient k1 and compression failure coefficient k2 are proposed by the mechanical analysis of the established filling body mechanics model, and when both k1 and k2 are less than 1, the roadside filling body can keep stable. The mechanical model of main roof is analyzed by the static equilibrium method, and the formula for calculating the maximum roof subsidence is deduced. Based on the data of haulage gateway of No. 21201 coal face of Juncheng Coal Mine, using the formula to calculate the amount of roof subsidence at the junction point of filling body and the roof, and proposes two methods to reduce roadway floor heave by increasing the roadside filling width and transferring the surrounding rock stress to the gob. Finally, the corresponding surrounding rock control technology is proposed according to the surrounding rock deformation characteristics during roadway excavation, roadway retention and roadway reuse, and then carries out field monitoring and evaluation. The results show that after adopting the corresponding supporting technology, the surrounding rock of the gob-side entry retaining has been effectively controlled from the excavation to the reuse period with the coal face advancing, the roof-to-floor convergence of roadway solid coal side is less than 220 mm, the roof-to-floor convergence of filling body side is less than 280 mm, and the convergence on the both sides of the roadway is about 190 mm. At the same time, the calculated roof subsidence with the junction point of filling body and the roof is similar to the field monitoring results, which achieves the expected control effect, and the research contents provides a certain reference for the support technology of the gob-side entry retaining.
Numerical investigation on rules of fracture propagation during hydraulic fracturing in heterogeneous coal-rock mass
Authors: Yuan Zhigang , Shao Yaohua , Xie Donghai , Huang Fei 
Published: July 2019

To investigate rules of fracture propagation during hydraulic fracturing in heterogeneous coal-rock mass, a new mathematical model for hydraulic fracturing with seepage-damage coupling and its numerical algorithm are proposed. The rules of coal-rock mass heterogeneity, confining pressure, beforehand hydraulic slotting, and non-symmetric pressure gradient on fracture propagation are investigated. Numerical results show the following: (1) Compared to homogeneous coal-rock mass, the fracture propagation pattern exhibits a more zig-zag characteristic and the fracture initiation pressure is reduced in heterogeneous coal-rock mass. (2) Fracture propagation during borehole fracturing is mainly controlled by confining pressure ratio, and the fracture would propagate along the path with least resistance in coal-rock mass. (3) During hydraulic fracturing with beforehand hydraulic slotting, fracture propagation pattern would become more complex with slotting length increasing; the propagation direction of fracture is primarily controlled by principal stress difference, the larger of principal stress difference, the more difficult of oriented fracturing. (4) Non-symmetric pressure gradient can reduce breakdown pressure and influence fracture propagation pattern, which provides a beneficial guide for oriented fracturing. The simulation results are consistent with the theoretical solutions and experimental observations, which is promising to guide field operation of hydraulic fracturing to improve coalbed methane extraction.
Lactoferrin in Bone Tissue Regeneration
Authors: Icriverzi Madalina , Dinca Valentina , Moisei Magdalena , Evans Robert W. , Trif Mihaela , Roseanu Anca 
Published: July 2019

:
Among the multiple properties exhibited by lactoferrin (Lf), its involvement in
bone regeneration processes is of great interest at the present time. A series of in vitro and
in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation
of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the
mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been
shown that its mode of action leading to the survival of osteoblasts is complemented by its
mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent
or independent manner, has been identified. Unlike the effects on osteoblasts, the
action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis.

:
Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination
with different biologically active compounds in bone tissue regeneration and the treatment of
bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology-
based strategy to improve the biological properties of Lf was developed. The investigated
formulations include incorporation of Lf into collagen membranes, gelatin hydrogel,
liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based
implants. Lf has also been coupled with other biologically active compounds such as
biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation
of bone homeostasis.

:
This review aims to provide an up-to-date review of research on the involvement of Lf in
bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.
The Ultrashort Peptide OW: A New Antibiotic Adjuvant
Authors: Al Tall Yara , Abualhaijaa Ahmad , Qaoud Mohammed T. , Alsaggar Mohammad , Masadeh Majed , Alzoubi Karem H. 
Published: July 2019

Background:The over use of current antibiotics and low discovery rate of the new ones are leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have shown promising results against multidrug-resistant bacteria.Objective:To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW).Methods:The OW hexapeptide was designed and tested against different strains of bacteria with different levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities of the hexapeptide were studied using the Biofilm Calgary method.Results:Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms of action. It showed an outstanding synergism with Rifampicin against methicillin resistant Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by 85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the MIC value of Ampicillin.Conclusion:This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential in the management of drug-resistant infectious diseases as a single agent or in combination with commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of these peptides.
The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients
Authors: Gaafar Nada A.G. , Aslani Mona , Aghazadeh Zahra , Razavi Alireza , Mirshafiey Abbas 
Published: July 2019

Background:
Rheumatoid Arthritis (RA) is a complex disease involving an unknown number
of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately
1% of the population worldwide. The safety and therapeutic efficacy of β-D-mannuronic acid
(M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in
vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to
phase I/11 and 111 in Rheumatoid Arthritis (RA) patients.

Objective:
In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000
on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase
(TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis.

Methods:
The study has included 15 RA patients who had an insufficient response to the conventional
drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a
single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15
healthy participants considered as control. Blood samples have been collected from both groups once
from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral
Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of
MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method.

Results:
The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients
after treatment with M2000 compared to before treatment. On the other hand, the gene expression level
of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared
to before treatment, but there was no significant difference between the group of RA patients before
treatment and the control group. Vice versa to other molecules, there was no significant difference in
the level of TIMP1 in compression with RA patients before and after treatment.

Conclusion:
our findings proved that the β -D- mannuronic acid) as a novel NSAID with immunosuppressive
property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2
molecules in RA patients.
Impact of Glycemic Variability and Hypoglycemia on the Mortality and Length of Hospital Stay among Elderly Patients in Brazil
Authors: Bruginski Danielle , Précoma Dalton Bertolin , Sabbag Ary , Olandowski Marcia 
Published: July 2019

Background:Glycemic variability (GV) is an alternative diabetes-related parameter that has been associated with mortality and longer hospitalization periods. There is no ideal method for calculating GV. In this study, we used standard deviation and coefficient of variation due to their suitability for this sample and ease of use in daily clinical practice.Objective:This study aimed to investigate the association between GV, hypoglycemia, and the 90-day mortality and length of hospital stay (LOS) among non-critically ill hospitalized elderly patients.Methods:The medical records of 2,237 elderly patients admitted to the Zilda Arns Elderly Hospital over a 2.5-year period were reviewed. Hypoglycemia was defined as a glucose level <70 mg/dL (hypoglycemia alert value) and represented by the proportion of days in which the patient presented with this condition relative to the LOS. The Charlson comorbidity index was used to evaluate prognosis. Data were analyzed using multiple linear and logistic multivariate regression analyses.Results:Adjusted analysis of 687 patients (305 men [44.4%] and 382 women [55.6%], mean age of 77.86±9.25 years) revealed that GV was associated with a longer LOS (p=0.048). Mortality was associated with hypoglycemia (p=0.005) and mean patient-day blood glucose level (p=0.036). Variables such as age (p<0.001), Charlson score (p<0.001), enteral diet (p<0.001), and corticosteroid use (p=0.007) were also independently associated with 90-day mortality.Conclusion:Increased GV during hospitalization is independently associated with a longer LOS and hypoglycemia in non-critically ill elderly patients, while the mean patient-day blood glucose is associated with increased mortality.
Intercycle Unplanned Hospital Admissions Due to Cisplatin-based Chemotherapy Regimen-induced Adverse Reactions: A Retrospective Analysis
Authors: Bright Heber Rew , Chandy Sujith J. , Chacko Raju Titus , Backianathan Selvamani 
Published: July 2019

Background:
Cisplatin is a commonly used chemotherapy agent known to induce serious adverse
reactions that may require hospital readmission. We aimed to analyze the extent and factors associated
with unplanned hospital admissions due to cisplatin-based chemotherapy regimen-induced adverse reactions.

Methods:
Retrospective review of medical records of those patients who received at least one cycle of
chemotherapy with cisplatin-based regimen during a six-month period from March to August 2017.

Results:
Of the 458 patients who received cisplatin during the study period, 142 patients did not meet inclusion
criteria. The remaining 316 patients had a total of 770 episodes of primary admissions for chemotherapy
administration. Overall, 187 episodes (24%) of intercycle unplanned hospital admission were recorded
of which a major proportion (n=178; 23%) was due to chemotherapy-induced adverse reactions. Underweight
patients had higher odds of unplanned admission (OR 1.77, 95% confidence interval [CI] 1.11 to
1.77). Significantly, more number of patients with cancers of head and neck and cancers of musculoskeletal
were readmitted (p<0.001). Compared to high-dose cisplatin, low- and intermediate-dose cisplatin had lesser
odds of unplanned admission (OR 0.52 and 0.77; 95% CI, 0.31 to 0.88 and 0.41 to 1.45, respectively).
Patients without concomitant radiotherapy, drug-drug interaction and initial chemotherapy cycles had lesser
odds of unplanned admission (OR 0.38, 0.50 and 0.52; 95% CI, 0.26 to 0.55, 0.25 to 0.99 and 0.32 to 0.84
respectively). Unplanned admissions were mainly due to blood-related (31%) and gastrointestinal (19%)
adverse reactions. Among chemotherapy regimens, cisplatin monotherapy (34%) and cisplatin with doxorubicin
(20%) regimens resulted in a major proportion of unplanned admissions.

Conclusion:
These findings highlight risk factors that help identify high-risk patients and suggest that therapy
modifications may reduce hospital readmissions due to cisplatin-based chemotherapy-induced adverse
reactions.
Penaksiran Heritabilitas Karakteristik Produksi dan Reproduksi Sapi Perah Friesen Holstein di BBPTU-HPT Baturraden
Authors: Krisnamurti Endah , Purwanti Dattadewi , Saleh Dadang Mulyadi 
Published: July 2019

Penelitian tentang evaluasi potensi genetik sapi Friesian Holstein (FH) telah dilaksanakan di BBPTU-HPT Baturraden Purwokerto. Penelitian ini dimulai pada bulan September sampai Desember 2018. Materi yang digunakan dalam penelitian ini sapi FH dan keturunannya F1 sebanyak 140 ekor. Metode yang digunakan dalam penelitian ini adalah menggunakan data recording mulai tahun 2010 sampai 2018. Variabel yang diamati adalah produksi susu, umur beranak pertama, kawin pertama setelah bernak, masa kosong, lama kebuntingan dan jarak beranak.Â Komponen ragam untuk menduga nilai heritabilitas sifat produksi dan reproduksi dengan menggunakan metode Regresi Anak â€“ Tetua. Hasil penelitian menunjukkan rataan produksi susu sapi FH di BBPTU-HPT Baturraden sebesar 4.733,02Â±1.181,18 kg/laktasi atauÂ 15,52Â±3,87 l/hari. Rataan sifat reproduksi (umur beranak pertama, kawin pertama setelah beranak, masa kosong, lama kebuntingan dan jarak beranak) masing-masing sebesar 772,19Â±77,51 hari; 130,03Â±70,72 hari; 201,87Â±104,67 hari; 278,05Â±14,75 hari dan 505,85Â±120,06 hari. Berdasarkan perhitungan secara umum nilai heritabilitas yang dihasilkan tergolong rendah sampai tinggi. Nilai heritabilitas produksi susu, umur beranak pertama, kawin pertama setelah beranak, masa kosong, lama kebuntingan dan jarak beranak masing-masing sebesar 0,43Â±0,19; 0,15Â±0,32; 0,10Â±0,34; 0,03Â±0,28; 0,17Â±0,30 dan 0,09Â±0,28.
Peran Protozoa pada Pencernaan Ruminansia dan Dampak Terhadap Lingkungan
Authors: Yanuartono Yanuartono , Nururrozi Alfarisa , Indarjulianto Soedarmanto , Purnamaningsih Hary 
Published: July 2019

Rumen adalah ekosistem yang sangat kompleks serta mengandung berbagai jenis mikroba. Kinerja ruminansia tergantung pada aktivitas mikroorganisme mereka untuk memanfaatkan asupan pakan. Namun demikian, aktivitas mikroba rumen juga merupakan sumber utama pembentukan gas metan dari bidang pertanian yang mengakibatkan efek rumah kaca. Protozoa rumen dengan penampilan yang cukup mencolok dianggap memiliki peran penting pada ruminansia sebagai hospes. Namun, terlepas dari kenyataan bahwa protozoa dapat menyumbang hingga 50% biomassa di rumen, peran protozoa sebagai salah satu mikroba dalam ekosistem rumen masih belum jelas. Meskipun peran protozoa masih belum jelas, namun protozoa dalam rumen terbukti memiliki hubungan dengan methanogen dan telah terbukti bahwa protozoa secara tidak langsung terlibat dalam produksi gas metan. Methanogen adalah satu-satunya mikroorganisme yang diketahui mampu memproduksi metan. Karena protozoa adalah penghasil hidrogen besar, yang digunakan sebagai substrat oleh simbion metanogennya untuk mengurangi karbon dioksida menjadi metana, dengan demikian dapat diasumsikan bahwa defaunasi mengurangi metanogenesis dengan jalan menurunkan kepadatan methanogen. Tulisan ini Â mencoba untuk mengevaluasi informasi terkini tentang peran protozoa di ekosistem mikroba rumen dan dampaknya terhadap lingkungan.
Evaluation of English language materials: One junior high school in Yogyakarta
Authors: Kiswaga Godlove Elioth , Triastuti Anita 
Published: July 2019

Teaching language in this global era demands mostly the creativity of the teachers, this is because in 21th century, students need to be critical thinkers, creative, communicative and collaborative. Therefore, the creativity of the teacher is manifested by evaluating the multiple resources and adapting or adopting them based on the contextualized learning situation including individual differences, styles and learners needs. It is also essential for the teacher to integrate the four macro skills in teaching language in order to make the students more communicative and collaborative. Hence, this paper presents the evaluation of the language teaching resources before and during applying them to the classroom contexts. The data were collected by document review, classroom observation and interview with the secondary school teacher. The data were analyzed qualitatively through interactive model. There is variation of the results based on the techniques of data collection. The interview shows that theoretically the teacher is creative to make the materials for students. Meanwhile, the observation and document review findings show that there is a need of improvement on the way to evaluate and use the English materials based on the context. Finally, we suggest that the theoretical knowledge from interview should be implemented practically in class and in evaluating the textbooks in order to adopt or adapt by adding or removing some materials to make English textbooks match with students contexts.
PHARMACOGNOSTIC STANDARDIZATION, PRELIMINARY PHYTOCHEMICAL SCREENING AND TLC FINGERPRINTING OF THE BARK OF CASCABELA THEVETIA L.
Authors: Gogoi Neelutpal , Bhuyan Biman , Deka Trinayan 
Published: July 2019

Objectives: In this study, systematic pharmacognostic study and preliminary phytochemical screening of the bark of Cascabela thevetia L. were carried out.
Methods: The selected plant part was collected, processed and stored in an airtight container. From the bark different pharmacognostic studies like macroscopic and microscopic evaluation, physicochemical parameters, fluorescence analysis were done. Powdered bark was successively extracted by petroleum ether, chloroform, ethyl acetate, and methanol using a Soxhlet apparatus and finally macerated with the hydro-alcoholic solvent system (30:70). The preliminary phytochemical analysis and thin layer chromatography of the extracts were done to find the nature and number of the different phytoconstituents present.
Results: Transverse microscopy reveals the presence of crystal oxalate, cork cell, starch granules, vascular bundle, phloem fiber, parenchyma cells, and collenchyma cells. Powder microscopy also showed the presence of cork cell, fiber and calcium oxalate crystal. Results obtained in different physicochemical analysis like total ash, acid insoluble ash, water soluble ash, alcohol-soluble extractive, water-soluble extractive, and moisture content were 8.67%, 0.83%, 5.33%, 4.53%, 12.27%, and 7.83% respectively. Phytochemical analysis showed the presence of alkaloid, flavonoid, triterpenoid, phytosterol, tannin, saponin, anthraquinone, carbohydrate and fatty acid in the different extracts. TLC (Thin Layer Chromatography) study revealed 4 spots in petroleum ether, chloroform, ethyl acetate, and methanol extracts and 3 spots in the Hydro-alcoholic extract with different solvent systems.
Conclusion: The results obtained from the study will provide a reliable basis for identification, purity, and quality of the plant.