bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a forecasting model for cholera incidence in Dhaka megacity through time series climate data
Authors: Daisy Salima Sultana , Saiful Islam A. K. M. , Akanda Ali Shafqat , Faruque Abu Syed Golam , Amin Nuhu , Jensen Peter Kjær Mackie 
Published: February 2020

Abstract
Cholera, an acute diarrheal disease spread by lack of hygiene and contaminated water, is a major public health risk in many countries. As cholera is triggered by environmental conditions influenced by climatic variables, establishing a correlation between cholera incidence and climatic variables would provide an opportunity to develop a cholera forecasting model. Considering the auto-regressive nature and the seasonal behavioral patterns of cholera, a seasonal-auto-regressive-integrated-moving-average (SARIMA) model was used for time-series analysis during 2000–2013. As both rainfall (r = 0.43) and maximum temperature (r = 0.56) have the strongest influence on the occurrence of cholera incidence, single-variable (SVMs) and multi-variable SARIMA models (MVMs) were developed, compared and tested for evaluating their relationship with cholera incidence. A low relationship was found with relative humidity (r = 0.28), ENSO (r = 0.21) and SOI (r = −0.23). Using SVM for a 1 °C increase in maximum temperature at one-month lead time showed a 7% increase of cholera incidence (p &lt; 0.001). However, MVM (AIC = 15, BIC = 36) showed better performance than SVM (AIC = 21, BIC = 39). An MVM using rainfall and monthly mean daily maximum temperature with a one-month lead time showed a better fit (RMSE = 14.7, MAE = 11) than the MVM with no lead time (RMSE = 16.2, MAE = 13.2) in forecasting. This result will assist in predicting cholera risks and better preparedness for public health management in the future.
Utilization of high solid waste activated sludge from small facilities by anaerobic digestion and application as fertilizer
Authors: Hidaka Taira , Nakamura Masato , Oritate Fumiko , Nishimura Fumitake 
Published: February 2020

Abstract
Anaerobic co-digestion of sewage sludge with organic wastes has recently gained attention in small facilities. For small facilities, high solids sludge is suitable for transportation to a centralized co-digester, and direct utilization of the digested sludge as liquid fertilizer is recommended. Effects of high solid and hyperthermophilic pretreatment (80 °C, 24 hr) on anaerobic digestion at low temperatures and utilization as fertilizer are investigated by anaerobic/aerobic digestion and paddy soil incubation experiments. The volatile solids (VS)/total solids (TS) ratio decreases to 0.57(-), and the VS removal rate is approximately 0.7 (-) after long-term aerobic digestion. This is possibly the limitation of biodegradation, even with pretreatment, within engineering time. Substrate TS of 16% (not diluted), 10% and 5% are compared. The effect of substrate TS on biogas production performance (0.2–0.3 NL/gVS-added) is not statistically observed. Laboratory-scale paddy soil incubation experiments are performed fed with anaerobically digested pretreated or not pretreated dewatered sludge as liquid fertilizer. Pretreatment promotes nitrogen mineralization before use as fertilizer, which is helpful to prevent an outflow of surplus ammonia to the environment. The effect of soil type on microbial communities is more significant than that of anaerobically digested sludge conditions.
Heterocycle Compounds with Antimicrobial Activity
Authors: Fesatidou Maria , Petrou Anthi , Athina Geronikaki 
Published: February 2020

Background:Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections.Objective:The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities.Method:To reach our goal, a literature survey that covers the last decade was performed.Results:As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned.Conclusion:It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.
Novel Polymethoxylated Chalcones as Potential Compounds Against KRAS-Mutant Colorectal Cancers
Authors: Mahmoud Alaa , Elkhalifa Dana , Alali Feras , Al Moustafa Ala-Eddin , Khalil Ashraf 
Published: February 2020

Background/Objective:KRAS-mutant colorectal cancers (CRC) are tumors that are associated with poor prognosis. However, no effective treatments are available to target them. Therefore, we designed and synthesized novel chalcone analogs, small organic molecules, to investigate their effects on KRAS-mutant CRC cells.Methods:Fourteen new chalcone analogs were synthesized, optimized, characterized, and tested against two KRAS-mutant CRC cell lines (HCT-116 and LoVo), one p-53 and BRAF mutant CRC cell line (HT-29) and one normal immortalized colon cells (NCE-1 E6/E7). Effects on cell viability, apoptosis, cell cycle, migration, colony formation, EMT, and angiogenesis were investigated.Results:Compounds 3 and 14 were the most effective. Compound 3 showed potent activity against HCT-116 and LoVo cell lines (GI50 of 6.10 μM and 7.00 μM, respectively). While compound 14 showed GI50 of 8.60 μM and 8.80 μM on HCT-116 and LoVo cell lines, respectively. Both compounds were approximately 2-3 times more selective toward cancer cells rather than normal colon cells. Compound 3 was effective in inducing apoptosis in HCT-116 cells via Bax upregulation and Bcl-2 downregulation. Invasion and metastasis of KRAS-mutant cells were modulated by compounds 3 and 14 through significant inhibition of cell migration and the prevention of colony formation. In addition, they reversed EMT by downregulation of EMT markers (vimentin, fascin, and β- catenin) and upregulation of cell-cell adhesion marker, E-cadherin. Furthermore, compounds 3 and 14 had significantly inhibited angiogenesis in ovo.Conclusion:Compounds 3 and 14 represent potent and selective leads for KRAS-mutant CRC cells, thus, further in vitro and in vivo studies are necessary to confirm their effect on KRAS-mutant CRCs.
Understanding Mass Spectrometry-based Global Mycobacterial Lipidomics
Authors: Fatima Zeeshan , Nandan Shiv , Hameed Saif 
Published: February 2020

:
Tuberculosis (TB) is the foremost cause of mortality from single infectious
agent Mycobacterium tuberculosis (MTB). Current therapeutic regimes suffer from
several problems, including side effects, costs and emergence of multidrug resistance
(MDR). Moreover, conventional diagnostic methods are either too slow, or lack accurate
and robust biomarkers. Under such circumstances, identification of rapid metabolite
based biomarkers as novel drug targets could be a potential approach to circumvent
MDR. In the era of “OMIC” sciences, lipidomics has gained significant attention to
unravel the complexity of lipid-loaded Mycobacterium species. Lipidomics is a subbranch
of metabolomics with extreme atomic diversity between the metabolites. There is
no single principle on which the metabolite diversity can be defined, unlike other
biomolecules viz. nucleic acid, proteins or carbohydrates. MTB encodes 10% of the
genome for lipid metabolism and lipids account for 60% of its dry weight. Mycobacterium
harbor a wide spectra of lipid repertoire ranging from highly apolar to highly polar lipids,
adding complexity to their identification and analysis. Compared to targeted
approaches, untargeted or global lipidomics of MTB is still more challenging. This review
describes recent advances in lipidomics technology with regard to chromatography,
detection methods and assessment on the existing mass spectrometry-based lipidomics
tools to study the untargeted or global MTB lipidomics. It also identifies the limitations
associated with present technologies as well as explores solutions to practical
challenges concurrent with the establishment of MTB lipidome. Together we endorse
that the emerging tools of lipidomics have provided a broader vision to comprehend the
role of lipid molecules in MTB pathogenesis and the need for further improvements.
Long-term Effects of Gastric Bypass Surgery in Patients with Obstructive Sleep Apnea
Authors: Obeidat Nathir , AlRyalat Saif Aldeen , Al Oweidat Khaled , Abu-Khalaf Mahmoud , Btoush Asma , Al-Essa Mohammad , Obeidat Zaina , Obeidat Mohammed , Wahbeh Ayman 
Published: February 2020

Background:
Obstructive sleep apnea is a common disorder involving, intermittent
mechanical obstruction of the upper airway during sleep. Obesity is the most powerful risk factor for
obstructive sleep apnea.

Objective:
This study aimed to investigate the long-term effect of Roux-en-Y gastric bypass bariatric
surgery on patients with obstructive sleep apnea.

Methods:
This study included patients were referred for bariatric surgery (Roux-en-Y gastric bypass)
to control symptoms and complications of obesity during a 5-year period. An overnight sleep study
was performed for each patient before and after the bariatric surgery, to study its effect on different
obstructive sleep apnea-related variables.

Results:
This study included 179 patients (mean age 35.9 ± 10.7 years). The mean duration from preoperative
assessment to postoperative assessment was 2.4 ± 2.2 years. The mean change in body
mass index and weight showed a decrease of 16.0 ± 16.0 kg/m2 and48.7 ± 25.9 kg, respectively. The
apnea hypopnea index decreased by a mean of 22.6 ± 26.3 events/hour.

Conclusion:
We concluded that a decrease in the body mass index by 1 kg/m2 could predict a
decrease in the apnea hypopnea index by 0.46 events/hour. Moreover, after mean follow-up duration
of 2.4 years, 84.3% of mild and 83.3% of moderate obstructive sleep apnea patients became normal
postoperatively.
Reducing the Burden of Diabetes Treatment: A Review of Low-cost Oral Hypoglycemic Medications
Authors: Vaughan Elizabeth M. , Rueda Jaime J. , Samson Susan L. , Hyman David J. 
Published: February 2020

Background:
The vast majority of individuals diagnosed with diabetes are low/middle income
and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost:
metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide,
glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to
potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or
dose-related.

Objective:
We conducted a narrative review of low-cost OHMs.

Results:
We evaluated the maximum recommended (MAX) compared to the most effective (EFF)
daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic
medications.

Results:
We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000
mg, EFF: 1,500–2,000/1,500–2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide
(MAX: 20 mg, EFF: 2.5–5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in
HbA1c levels occurred at weeks 12–20 (sulfonylureas), 25–39 (metformin), and 25 (pioglitazone).
Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative
to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses
(p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment.

Conclusion:
Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at
the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as
individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride
is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.
The Role of Natural Killer Cells and Mast Cells in Female Infertility and Associated Treatment Outcomes
Authors: Lorzadeh Nahid , Kazemirad Nastaran 
Published: February 2020

Introduction:
One of the identified causes of infertility has been related to the inability
to regulate immunological tolerance of the maternal immune system against the developing fetus,
thereby inhibiting the process of implantation. Various immune cells have been identified to contribute
to the concept of un-regulated immunological tolerance, such as mast cells (MCs) and natural
killer cells (NK). There are available evidences that MC play a role in the pathogenesis of infertility
diseases like endometriosis and NK in specific infertility disease.

Objective:
Presently, there are studies to formulate and develop immunosuppressive drugs in order
to suppress or inhibit the process of immune rejection caused by maternal immune cells. In addition,
there have been reports regarding the use of steroids for the treatment of miscarriage that can
inhibit the activity of most immune cells.

Conclusion:
This review is to give a comprehensive mini-review on the role of immune cells, especially
mast cells and NK cells in developing novel infertility treatment.
Design, Synthesis and Antitumor Assessment of Phenylureas Bearing 5-Fluoroindolin-2-one Moiety
Authors: Cai Yunrui , Chen Tong , Zhu Huajian , Zou Hongbin 
Published: February 2020

Background:
The development of novel antineoplastic agents remains highly desirable.

Objective:
This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas
bearing 5-fluoroindolin-2-one moiety.

Methods:
Three sets of phenylureas were designed and synthesized and their antiproliferative ability
was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via
MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast
cancer (MCF-7).

Results:
A total of twenty-one new compounds were synthesized and characterized by means of
1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially
constructed, and preliminary antiproliferative activities of these molecules were evaluated
against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as
the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed
and synthesized for structure-activity relationship study. Most of the new compounds
showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic
effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM.
Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF-
7) xenograft models without affecting the body weight of its recipients.

Conclusion:
In this study, twenty-one new compounds, containing the privileged structures of
phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity
studies showed that 1g was the most bioactive antitumor agent among all tested compounds,
hence a potentially promising lead compound once given further optimization.
Study of Pharmaceutical Excipient PEG400 Alteration of Pharmacokinetics and Tissue Distribution of Main Flavonoids Metabolites of Baicalin
Authors: Zhu Ya-Nan , Zhang Shuo , Zhang Min , Meng Xiao-Xia , Wang Peng-Jiao , Zhang Rong-Ping , Gao Xiu-Li 
Published: February 2020

Background::
Polyethylene glycol 400 (PEG400), as a good traditional Chinese medicine
solvent, diluent and solubilizer, is widely used as a main pharmaceutical excipient in traditional Chinese
medicine compound preparations containing active ingredient baicalin. PEG400 could increase
the solubility and release of baicalin in vivo, but it was unknown that PEG400 affected the absorption
and distribution of baicalin or not.

Objective: :
At present, the effects of PEG400 on the pharmacokinetic characteristics and tissue distribution
behaviors of the main flavonoid metabolites baicalin, baicalein 6-O-β-D-glucopyranoside (B6G)
and baicalein after oral administration of baicalin were investigated by a rapid, efficient and sensitive ultra-
high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method.
Moreover, we respectively studied the effects of PEG400 on the activities and protein expressions of two
subtypes UDP-glucuronyltransferase 1 A8/A9 (UGT1A8 and UGT1A9) of UDP-glucuronosyltransferases
(UGTs) in vitro and in vivo experiments to determine the partial mechanisms by which PEG400 altered
the pharmacokinetics and tissue distribution behaviors of the three flavonoid metabolites.

Methods:
A rapid, efficient and sensitive ultra-high performance liquid chromatography with tandem
mass spectrometry (UPLC-MS/MS) method and ELISA and so on.

Results:
The results showed that PEG400 significantly increased the Cmax and AUC0-t values
(P < 0.05 or P < 0.01) of baicalin and B6G while baicalein could not be quantified due to its extremely
low concentration (lower the LLOQ) in plasma. Baicalin, B6G and baicalein were mainly distributed in
the stomach, small intestine, kidney and liver. PEG400 changed the distribution of three flavonoid metabolites
in various tissues and also increased the activities and expressions of UGT1A8 and UGT1A9.

Conclusion::
In conclusion, PEG400 significantly altered the pharmacokinetic characteristics and tissue distribution
behaviors of three flavonoid metabolites may partly result from PEG400 upregulated the activities
and expressions of the drug biphasic metabolic enzymes UGT1A8 and UGT1A9, which provided a material
basis and useful information to reveal the mechanism of action and clinical application of PEG400.
A Rapid and Selective UPLC-MS/MS Assay for Accurate Analysis of Apatinib in Rat Plasma and its Application to a Pharmacokinetic Study
Authors: Gao Jinglin , Feng Zhangying , Ren Huan , Yu Mengdi , Wang Haidong , Wang Mingxia 
Published: February 2020

Objective:
Apatinib, a novel small-molecule Tyrosine Kinase Inhibitor (TKI), is under development
to treat advanced gastric cancer. For the pharmacokinetic evaluation and routine drug monitoring
of apatinib, a quantitative ultra-performance liquid chromatography coupled with tandem mass
spectrometry (UPLC-MS/MS) method in rat plasma was developed with tinidazole used as an internal
standard (IS).

Methods::
Protein precipitation (PPT) was selected as a sample pre-treatment method to extract apatinib.
Then, chromatography was performed on a Kinetex C8 column (2.1×100 mm, 2.6 μm) using a constant
mobile phase including 0.2% formic acid and 10 mM ammonium acetate in water and methanol
(30:70, v/v) with a gradient flow rate from 0.2 mL/min to 0.4 mL/min. Chromatographic analysis was
performed in only 4.5 min. Mass spectrometric detection was carried on positive electrospray ionization
(ESI+) mode with Multiple-Reaction Monitoring (MRM).

Results:
The standard calibration curve showed good linearity in 2-1000 ng/mL with the correlation
coefficient (R2) > 0.99. The Lower Limit of Quantitation (LLOQ) was 2 ng/mL. The precision, accuracy,
extraction recovery, matrix effect, stability and carryover were all within the acceptable range.

Conclusion:
This method was simple, accurate, selective and successfully used for a pharmacokinetic
study following seven rats orally administrated a single of 60 mg/kg apatinib.
Metabolite Fingerprinting of Novel Streptomyces UK-238 from the Himalayan Forest
Authors: Srivastava Nidhi , Sarethy Indira P. 
Published: February 2020

Aims:
Characterization of antimicrobial metabolites of novel Streptomyces sp. UK-238.

Background:
Novel antimicrobial drug discovery is urgently needed due to emerging multi antimicrobial
drug resistance among pathogens. Since many years, natural products have provided the basic
skeletons for many therapeutic compounds including antibiotics. Bioprospection of un/under explored
habitats and focussing on selective isolation of actinobacteria as a major reservoir of bio and chemodiversity
has yielded good results.

Objective:
The main objectives of the study were the identification of UK-238 by 16S rDNA sequencing
and antimicrobial metabolite fingerprinting of culture extracts.

Methods:
In the present study, a promising isolate, UK-238, has been screened for antimicrobial activity
and metabolite fingerprinting from the Himalayan Thano Reserve forest. It was identified by 16S
rDNA sequencing. Ethyl acetate extract was partially purified by column chromatography. The pooled
active fractions were fingerprinted by GC-MS and compounds were tentatively identified by collated
data analysis based on Similarity Index, observed Retention Index from Databases and calculated Retention
Index.

Results:
UK-238 was identified as Streptomyces sp. with 98.4% similarity to S. niveiscabiei. It exhibited broad-spectrum antibacterial and antifungal activity. GC-MS analysis of active fractions of ethyl acetate extract showed the presence of eighteen novel antimicrobial compounds belonging to four major categories- alcohols, alkaloid, esters and peptide.

Conclusion:
The study confirms that bioprospection of underexplored habitats can elaborate novel bio
and chemodiversity.
MSIT: Malonylation Sites Identification Tree
Authors: Bao Wenzheng , Huang De-Shuang , Chen Yue-Hui 
Published: February 2020

Aims:Post-Translational Modifications (PTMs), which include more than 450 types, can be regarded as the fundamental cellular regulation.Background:Recently, experiments demonstrated that the lysine malonylation modification is a significant process in several organisms and cells. Meanwhile, malonylation plays an important role in the regulation of protein subcellular localization, stability, translocation to lipid rafts and many other protein functions.Objective:Identification of malonylation will contribute to understanding the molecular mechanism in the field of biology. Nevertheless, several existing experimental approaches, which can hardly meet the need of the high speed data generation, are expensive and time-consuming. Moreover, some machine learning methods can hardly meet the high-accuracy need in this issue.Methods:In this study, we proposed a method, named MSIT that means malonylation sites identification tree, utilized the amino acid residues and profile information to identify the lysine malonylation sites with the tree structural neural network in the peptides sequence level.Methods:The proposed algorithm can get 0.8699 of F1 score and 89.34% in true positive ratio in E. coli. MSIT outperformed existing malonylation site identification methods and features on different species datasets.Conclusion:Based on these measures, it can be demonstrated that MSIT will be helpful in identifying candidate malonylation sites.