bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Induction of Apoptosis in ESCC (Esophageal Squamous-Cell Carcinoma) by Betula pendula Roth Stem Cell Extract Containing Triterpenoids Compared to Doxorubicin
Authors: Nazari Jamile , Payamnoor Vahide , Sadeghzadeh Zahra , Asadi Jahanbakhsh , Kavosi Mohammad R. 
Published: August 2020

Background:
Esophageal Squamous-Cell Carcinoma (ESCC) is one of the most life-threatening
malignancies worldwide, with a growing incidence in Iran higher than the global average.

Objective:
The present study, for the first time under patent number (97668), introduces a method using in vitro
production of activated-Birch stem cells using biotechnological techniques of tissue culture and plant stem cell
culture from Betula pendula Roth (Birch) bark.

Methods:
In the first step, Birch stem cells were produced in large amounts using tissue culture, and then the
amount of triterpenoids of its extract was measured by the HPLC method. In the second step, the cytotoxicity
was evaluated by MTT, and the IC50 was calculated. The cellular apoptosis in response to the extract compared
to doxorubicin was measured using the Annexin V kit and the flow cytometry method.

Results:
The optimized method introduced in the current study efficiently produced plant stem cells containing
triterpenoids in large quantities over a period of 2-4 months. Our findings indicated that the growth of ESCC
cells decreased by induction treatment 3 times (24, 36, 48 hours). IC50 values were obtained in 24 hours for the
natural bark extract, Birch stem cell extract, doxorubicin and interactions of two extracts with doxorubicin at
300μg/mL, 1700μg/mL, 0.5μM, 150μg/mL, 1800μg/mL, respectively. In the flow cytometric test, the Birch
stem cell extract showed the highest percentage of apoptosis, with 92.5% for total apoptosis. The percentage of
total apoptosis in doxorubicin treatment was 85.33%, and the combination of doxorubicin with Birch stem cell
extract was 88.33%. Natural bark extract and its combination with a lower percentage (69.33% and 70.33%,
respectively) caused apoptosis of esophageal cancer cells.

Conclusion:
Owing to the extinction of Birch in Iran and its inaccessibility and exploitation, Birch stem cells
can be cultured as an appropriate alternative source to produce valuable triterpenoids for pharmaceutical
purposes. Additionally, according to the results of this study, stem cells can be used to enhance the treatment of
esophageal cancer and supplementation with chemotherapy.
Nuciferine Inhibits Skin Cutaneous Melanoma Cell Growth by Suppressing TLR4/NF-κB Signaling
Authors: Xu Jingxing , Ying Anxin , Shi Tongxin 
Published: August 2020

Background:
Melanoma causes more than 80% of deaths from all dermatologic cancers. Hence,
screening and identifying effective compounds to inhibit the growth of melanoma have crucial importance in
basic and clinical treatment.

Methods:
High throughput screening was performed to screen and identify compounds that have anti-melanoma
ability. Melanoma cell and mouse allograft models were used to examine the anti-tumor effects of Nuciferine
(NCFR). Western blot, qPCR, and lentivirus overexpression were applied to detect the activation of the
TLR4/NF-κB signaling pathway.

Results:
NCFR administration significantly suppressed melanoma cell growth and tumor size by inhibiting the
phosphorylation of p65. NCFR treatment also could suppress TNF-α-induced activation of NF-κB signaling.
The anti-tumor effect of NCFR might be mediated by targeting Toll-like receptors 4.

Conclusion:
NCFR inhibits melanoma cell growth and suppresses tumor size, which provides potential therapeutic
strategies for melanoma treatment.
Leaf Extract of Nerium oleander L. Inhibits Cell Proliferation, Migration and Arrest of Cell Cycle at G2/M Phase in HeLa Cervical Cancer Cell
Authors: Mohapatra Shubhasmita , Biswal Anil K. , Dandapat Jagnehswar , Debata Priya R. 
Published: August 2020

Background:
Cervical cancer is one of the most common gynaecological malignant tumors reported
in women. Although a number of early screening and treatment options are available, mortality due to cervical
cancer remains high. Nerium oleander L. is a potential medicinal plant that possesses a wide spectrum of pharmacological
and physiological activities including anticancer activities.

Objective:
This study aims to evaluate the antiproliferative activity, inhibition of cell migration and cell cycle
arrest by the chloroform extract of leaves of Nerium Oleander L. in HeLa cervical cancer cells. The chloroform
extract of Catharanthus roseus which contains anti-cancer compounds, Vinblastin and Vincristin, was used as a
positive control for this study.

Methods:
The chloroform extracts of Nerium oleander L. and Catharanthus roseus were prepared using the
standard protocol. The cytotoxic effects were studied by MTT assay. Cell migration was studied by in vitro
scratch assay. Analysis of the cell cycle was carried out by Propidium iodide staining and Flow Cytometry. The
expression level of various proteins was evaluated by immunocytochemistry.

Results:
In this study, we showed that the leaf extract of Nerium oleander inhibited the growth of HeLa cervical
cancer cells in culture and inhibited cell migration. Besides, it arrested the cell cycle at the G2/M phase. The
Epidermal Growth Factor Receptor (EGFR) expression and phosphorylated p-Rb (Ser 780) level were significantly
downregulated by leaf extract of Nerium oleander.

Conclusion:
The extract of Nerium oleander L. contains potential bioactive compounds that inhibit HeLa cell
proliferation, cell migration and arrest cell cycle at the G2/M phase.
Antiproliferative Activity and Apoptotic Efficiency of Syzygium cumini Bark Methanolic Extract against EAC Cells In Vivo
Authors: Siddika Ayesha , Das Plabon K. , Asha Saharia Y. , Aktar Suraiya , Tareq Abu R.M. , Siddika Ayesha , Rakib Abdur , Islam Farhadul , Khanam Jahan Ara 
Published: August 2020

Background:
Syzygium cumini is one of the evidence-based traditional medicinal plant used in the
treatment of various ailments.

Objectives:
Herein, the antioxidant property and anticancer property of Syzygium cumini against Ehrlich Ascites
Carcinoma (EAC) cells were examined to find effective chemotherapeutics.

Methods:
In vitro assays, and phytochemical and chromatographic analyses were used to determine antioxidant
properties and chemical constituents of Syzygium cummini Bark Methanolic Extract (SCBME). Functional assays
were used to measure the anticancer activity of SCBME. Fluorescence microscopy and RT-PCR were used
to examine morphological and molecular changes of EAC cells followed by SCBME treatment.

Results:
Phytochemical and GC-MS analyses confirmed the presence of compounds with antioxidant and anticancer
activities. Accordingly, we have noted a strong antioxidant activity of SCBME with an IC50 value of
~10μg/ml. Importantly, SCBME exerted a dose-dependent anticancer activity with significant inhibition of EAC
cell growth (71.08±3.53%; p<0.001), reduction of tumor burden (69.50%; p<0.01) and increase of life span
(73.13%; p<0.001) of EAC-bearing mice at 75mg/kg/day. Besides, SCBME restored the blood toxicity towards
normal in EAC-bearing mice (p<0.05).

Discussion:
SCBME treated EAC cells showed apoptotic features under a fluorescence microscope and fragmented
DNA in DNA laddering assay. Moreover, up-regulation of the tumor suppressor p53 and pro-apoptotic
Bax and down-regulation of NF-κB and anti-apoptotic Bcl-2 genes implied induction of apoptosis followed by
SCBME treatment.

Conclusion:
The antiproliferative activity of SCBME against EAC cells is likely due to apoptosis, mediated by
regulation of p53 and NF-κB signaling. Thus, SCBME can be considered as a useful resource in cancer chemotherapy.
Self-emulsifying Drug Delivery System Improve Oral Bioavailability: Role of Excipients and Physico-chemical Characterization
Authors: Zhu Yujin , Ye Jing , Zhang Quan 
Published: August 2020

:
Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation
composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion
(micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed
emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in
SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore,
SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble
drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous
system, consequently being suitable for large-scale production and more stable than
conventional emulsion. However, the role of formulation aspects in the biological property
of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug
bioavailability, we need to fully understand the various factors that affect the in vivo behavior
of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant
and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also
discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS
on the oral drug bioavailability enhancement. This review would provide an approach to
develop a rational SEDDS to improving oral drug bioavailability.

Lay Summary:
Self-emulsifying drug-delivery system (SEDDS) has been proven to be
promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review
highlighted the influence of excipients and physicochemical property of SEDDS on the
formation of emulsion and the oral absorption of drugs in the body.
Microwave-assisted Homogeneous Gold Catalyzed Organic Transformations
Authors: Panda Biswajit 
Published: August 2020

:
Microwave chemistry is an emerging area of science mainly focusing on various applications
of microwave energy into chemical processes. Microwave irradiation has enormous potential to
provide controlled energy directly to the molecules of interest. On the other hand, homogeneous gold
catalysis has emerged in the last two decades or so as one of the most promising fields in organic and
organometallic chemistry. Its efficacy has been established many times for the construction of new C
– X (X = O, N, S, etc.) and C – C bonds under mild reaction conditions. Although a significant number
of reports have appeared in the literature regarding the homogeneous gold-catalyzed organic transformations
under microwave conditions, this is the first review article which is going to appear in the
literature. This mini-review is designed to give an interesting insight into various homogeneous goldcatalyzed
organic reactions under microwave irradiation for the synthesis of a library of electronically
and structurally diverse and biologically important organic molecules.
Cultural Impact on the Intention to Use Nursing Information Systems of Nurses in Taiwan and China: Survey and Analysis
Authors: Chang I-Chiu , Lin Po-Jin , Chen Ting-Hung , Chang Chia-Hui 
Published: August 2020

Background
Nursing workforce shortage has emerged as a global problem. Foreign nurse importation is a popular strategy to address the shortage. The interactions between nursing staff on either side of the Taiwan Strait continue to increase. Since both nurses in Taiwan and nurses in China have adopted nursing information systems to improve health care processes and quality, it is necessary to investigate factors influencing nursing information system usage in nursing practice.

Objective
This study examined the effects of cultural and other related factors on nurses’ intentions to use nursing information systems. The findings were expected to serve as an empirical base for further benchmarking and management of cross-strait nurses.

Methods
This survey was conducted in two case hospitals (one in Taiwan and one in China). A total of 880 questionnaires were distributed (n=440 in each hospital).

Results
The results showed effort expectancy had a significant effect on the intention to use nursing information systems of nurses in China (P=.003) but not nurses in Taiwan (P=.16).

Conclusions
Findings suggest nursing managers should adopt different strategies to motivate cross-strait nurses to use nursing information systems. Promoting effort expectancy is more likely to motivate nurses in China than in Taiwan. This discrepancy is probably due to the less hierarchical and more feminine society in Taiwan.
Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data
Authors: Leal Jose , Reed Shelby D. , Patel Rishi , Rivero-Arias Oliver , Li Yanhong , Schulman Kevin A. , Califf Robert M. , Holman Rury R. , Gray Alastair M. 
Published: August 2020

OBJECTIVE
To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study.

RESEARCH DESIGN AND METHODS
We simulated the impact of delaying diabetes onset by 1–9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs.

RESULTS
Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567–$2,680 and £201–£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years.

CONCLUSIONS
Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.
Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study
Authors: Coppelli Alberto , Giannarelli Rosa , Aragona Michele , Penno Giuseppe , Falcone Marco , Tiseo Giusy , Ghiadoni Lorenzo , Barbieri Greta , Monzani Fabio , Virdis Agostino , Menichetti Francesco , Del Prato Stefano ,   Pisa COVID-19 Study Group, Sabrina Agostini o Degl’Innocenti , Rachele Antognoli , Rubia Baldassarri , Pietro Bertini , Martina Biancalana , Matteo Borselli , Giulia Brizzi , Valeria Calsolario , Laura Carrozzi , Alessandro Celi , Francesco Cinotti , Alessandro Cipriano , Francesco Corradi , Salvatore De Marco , Alessandra Della Rocca , Francesco Forfori , Giovanna Forotti , Valentina Galfo , Fabio Guarracino , Paolo Malacarne , Stefano Masi , Alessandro Mengozzi , Marco Monfroni , Alessandra Morea , Elia Nencini , Naria Park , Simone Paterni , Chiara Piagnani , Francesca Ruberti , Massimo Santini , Maria Sciuto , Stefano Spinelli 
Published: August 2020

OBJECTIVE
To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19).

RESEARCH DESIGN AND METHODS
Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels &lt;7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38–6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67–12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18–10.47]).

RESULTS
Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27–3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92–3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P = 0.079) vs. Q1.

CONCLUSIONS
Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.
Pemberdayaan Masyarakat Berbasis Pengembangan Usaha Mikro, Kecil, dan Menengah di Era Revolusi Industri 4.0
Authors: Wastutiningsih Sri Peni , Dewi Titis Puspita 
Published: August 2020

Era revolusi 4.0 mendorong masyarakat untuk memanfaatkan internet sebagai wahana digital marketing. Masyarakat utamanya yang bergerak di bidang usaha mikro, kecil, dan menengah (UMKM) memiliki jangkauan pasar yang lebih luas dengan penggunaan internet atau pemasaran berbasis online lainnya. Hal tersebut mendorong akademisi sebagai bagian dari masyarakat untuk berperan aktif dalam menginisiasi, mendorong, dan mendampingi realisasi digital marketing tersebut, salah satunya telah dilakukan tim UGM di Desa Giriharjo, Kecamatan Panggang, Kabupaten Gunungkidul, Daerah Istimewa Yogyakarta. Masyarakat Desa Giriharjo memiliki potensi usaha pangan lokal maupun handycraft yang dapat dikembangkan melalui digital marketing. Penelitian ini merupakan penelitian kualitatif dengan tujuan mengidentifikasi fungsi dan dampak digital marketing yang telah diterapkan dalam proses pemberdayaan masyarakat. Adapun hasil penelitian menunjukkan adanya fungsi manifes berupa peningkatan jumlah penjualan dan omzet yang diperoleh pengusaha melalui digital marketing sedangkan fungsi latennya berupa perubahan gaya hidup masyarakat perdesaan yang menjadi konsumtif semenjak mengenal dunia internet.
Persepsi Petani Terhadap Program Upsus Pajale Di Kecamatan Natar Kabupaten Lampung Selatan
Authors: Chyntia Bella , Gultom Dame Trully , Prayitno Rio Tedi 
Published: August 2020

Penelitian ini bertujuan untuk mengetahui tingkat keberhasilan, persepsi petani dan faktor-faktor yang berhubungan dengan persepsi petani terhadap Program Upsus Pajale. Penelitian ini dilakukan di Kecamatan Natar Kabupaten Lampung Selatan. Sampel dalam penelitian ini berjumlah 51 orang petani responden yang dipilih secara acak. Metode analisis data menggunakan analisis deskriptif kuantitatif, tabulasi, dan Korelasi Rank Spearman. Hasil penelitian menunjukkan bahwa Program Upsus Pajale belum berhasil. Sebagian besar petani belum menerapkan tahapan-tahapan dari Program Upsus Pajale, petani jarang mengikuti rapat terkait pelaksanaan program, serta produktivitas padi mengalami penurunan dari tahun 2018 sebesar 2,42 ton/ha/musim tanam dan produktivitas jagung mengalami penurunan dari tahun 2018 sebesar 2,30 ton/ha/musim tanam. Persepsi petani tentang Program Upsus Pajale sangat baik, karena penyuluh pertanian lapangan maupun ketua kelompok tani cukup sering memberi informasi tentang Program Upsus Pajale. Petani cukup tahu mengenai tujuan, ruang lingkup, dan sistem pendanaan pada Program Upsus Pajale. Faktor-faktor yang berhubungan dengan persepsi petani dalam Program Upsus Pajale adalah pengalaman berusahatani, motivasi, dan tingkat pengetahuan.
Kata kunci: penyuluhan, persepsi, produktivitas, Program Upsus Pajale
Persepsi Anggota, Dinamika Kelompok Pengelola Dan Pelestari Hutan (KPPH) dan Kelestarian Taman Hutan Raya (Tahura) di Kecamatan Kemiling Kota Bandar Lampung
Authors: Umar Ajay Khotib , Syarief Yuniar Aviati , Hasanuddin Tubagus , Nurmayasari Indah 
Published: August 2020

Taman Hutan Raya (Tahura) memiliki beragam fungsi. Untuk melestarikan Tahura dibentuk Kelompok Pengelola dan Pelestari Hutan (KPPH). Tujuan penelitian ini adalah untuk mengetahui (1) persepsi anggota KPPH terhadap kelestarian Tahura, (2) dinamika kelompok KPPH, (3) Tingkat kelestarian Tahura, (4) hubungan persepsi anggota KPPH dengan dinamika kelompok KPPH, (5) hubungan persepsi anggota KPPH dengan kelestarian Tahura, dan (6) hubungan dinamika kelompok KPPH dengan kelestarian Tahura. Penelitian dilakukan di Kelurahan Sumber Agung, Kota Bandarlampung dari bulan Maret-April 2019. Responden penelitian adalah anggota KPPH yang dipilih secara acak sebanyak 83 responden. Metode penelitian yang digunakan adalah metode survey. Analisis digunakan metode deskriptif dan statistik non parametrik. Hasil penelitian menunjukkan: (1) Persepsi anggota KPPH terhadap kelestarian Tahura cukup baik, (2) dinamika kelompok KPPH cukup dinamis, (3) Tingkat kelestarian Tahura cukup baik, (4) Persepsi anggota KPPH berhubungan dengan dinamika kelompok KPPH, (5) Persepsi anggota KPPH berhubungan dengan kelestarian Tahura, dan (6) Dinamika kelompok KPPH berhubungan dengan kelestarian Tahura.
Kata kunci: dinamika kelompok, kelestarian, persepsi, Tahura
Kesetaraan Gender pada Rumah Tangga Petani Padi Sawah di Kecamatan Gading Rejo Kabupaten Pringsewu
Authors: Nurmayasari Indah , Mutolib Abdul , Damayanti Nur Alfi Laila , Safitri Yuli 
Published: August 2020

Penelitian bertujuan untuk mengetahui peran perempuan dan faktor-faktor yang mempengaruhi kesetaraan gender dalam rumah tangga petani padi sawah di Pekon Wonodadi Kecamatan Gading Rejo Kabupaten Pringsewu. Penelitian menggunakan pendekatan kualitatif dengan 30 sampel petani padi sawah. Data yang digunakan adalah data primer dan data sekunder. Analisis data menggunakan pendekatan kesetaraan gender model Harvard. Tingkat kesetaraan gender dalam rumah tangga petani padi sawah diukur melalui pendekatan profil aktifitas yang meliputi: 1) pembagian kerja reproduktif, 2) pembagian kerja produktif, dan 3) pembagian kerja social. Profil akses dan kontrol terhadap sumberdaya dan manfaat diidentifikasi melalui: 1) tingkat kesetaraan dalam akses terhadap sumberdaya, 2) tingkat kesetaraan dalam akses terhadap manfaat, 3) tingkat kesetaraan dalam kontrol terhadap sumberdaya, dan 4) tingkat kesetaraan dalam kontrol terhadap manfaat. Penelitian dilaksanakan pada bulan Agustus hingga September 2019. Hasil penelitian memberikan gambaran bahwa aktivitas usahatani padi sawah baik dalam kegiatan produktif, maupun sosial didominasi oleh laki-laki. Perempuan dominan dalam kegiatan reproduktif. Kesetaraan gender dalam akses dan kontrol terhadap sumber daya dan manfaat didominasi laki-laki. Faktor-faktor yang memengaruhi kesetaraan gender meliputi: faktor budaya, tingkat pendidikan, ketidakpercayaan diri perempuan, dan tingkat ekonomi atau pendapatan rumah tangga petani padi sawah.
Respon Petani Padi Terhadap Program Billing System Pupuk Bersubsidi di Kecamatan Candipuro Kabupaten Lampung Selatan
Authors: Rahmalina Rahmalina , Nikmatullah Dewangga , Silviyanti Serly 
Published: August 2020

Salah satu program pemerintah untuk meminimalisir distribusi pupuk bersubsidi yang tidak tepat waktu dan tidak tepat sasaran program billing system. Penelitian ini bertujuan untuk mengetahui faktor-faktor yang berhubungan dengan respon petani padi pada program billing system. Penelitian dilakukan di Kecamatan Candipuro, Kabupaten Lampung Selatan. Pengambilan sampel menggunakan teknik purposive sampling, yaitu petani peserta program billing system yang berjumlah 93 orang. Jenis data yang digunakan dalam penelitian ini adalah data primer dan sekunder. Waktu pengambilan data penelitian dilaksanakan pada bulan Oktober 2019. Pengujian hipotesis dilakukan dengan menggunakan analisis peringkat korelasi rank Spearman. Hasil penelitian menunjukkan bahwa respon petani terhadap program billing system dilihat dari manfaat, pelaksanaan dan aksesibilitas program masuk dalam kategori baik. Faktor-faktor yang berhubungan secara signifikan dengan respon petani terhadap program billing system adalah tingkat pengetahuan, tingkat pemenuhan syarat program, dukungan pemerintah dan kepemilikan modal petani untuk menebus pupuk subsidi.