bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Lipoproteins-Nanocarriers as a Promising Approach for Targeting Liver Cancer: Present Status and Application Prospects
Authors: Alanazi Saleh A. , Alanazi Fars , Haq Nazrul , Shakeel Faiyaz , Badran Mohamed M. , Harisa Gamaleldin I.
Published: February 2020

The prevalence of liver cancer is increasing over the years and it is the fifth leading cause of
mortality worldwide. The intrusive features and burden of low survival rate make it a global health issue
in both developing and developed countries. The recommended chemotherapy drugs for patients in the
intermediate and advanced stages of various liver cancers yield a low response rate due to the nonspecific
nature of drug delivery, thus warranting the search for new therapeutic strategies and potential drug
delivery carriers. There are several new drug delivery methods available to ferry the targeted molecules
to the specific biological environment. In recent years, the nano assembly of lipoprotein moieties (lipidic
nanoparticles) has emerged as a promising and efficiently tailored drug delivery system in liver cancer
treatment. This increased precision of nano lipoproteins conjugates in chemotherapeutic targeting offers
new avenues for the treatment of liver cancer with high specificity and efficiency. This present review is
focused on concisely outlining the knowledge of liver cancer diagnosis, existing treatment strategies,
lipoproteins, their preparation, mechanism and their potential application in the treatment of liver cancer.
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.
The Cell Engraftment Hypothesis of Cardiac Repair
Authors: Davis Darryl R.
Published: February 2020

Heart failure is a significant source of morbidity and mortality around the world. Recently,
cell therapy has garnered much attention as a means for improving cardiac function after injury. Despite
years of study, a growing list of failed efficacy trials has led many to question the translatability
of preclinical work. In this review, we critically evaluate the evidence supporting the need for transplanted
cells to engraft and persist in the impaired heart (the cell engraftment hypothesis). We explore
how the complex interplay between cell retention, persistence and paracrine potency explains many of
the recent cell treatment outcomes. Through this discussion, we outline a framework to understand how
future approaches will optimize and personalize the methods, payloads and timing of cardiac cell delivery
for the millions of patients worldwide suffering from heart failure.
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.
3,4,5-Trihydroxybenzoic Acid Attenuates Ligature-Induced Periodontal Disease in Wistar Rats
Authors: Karatas Ozkan , Gevrek Fikret
Published: February 2020

Background:

3,4,5-Trihydroxybenzoic acid, which is also known as gallic acid, is an antiinflammatory agent that could provide beneficial effects in preventing periodontal inflammation. The present study aimed to evaluate the anti-inflammatory effects of gallic acid on experimental periodontitis in Wistar rats. Alveolar bone loss, osteoclastic activity, osteoblastic activity, and collagenase activity were also determined.

Methods:

Thirty-two Wistar rats were used in the present study. Study groups were created as following: Healthy control (C,n=8) group; periodontitis (P,n=8) group; periodontitis and 30 mg/kg gallic acid administered group (G30,n=8); periodontitis and 60 mg/kg gallic acid administered group (G60,n=8). Experimental periodontitis was created by placing 4-0 silk sutures around the mandibular right first molar tooth. Morphological changes in alveolar bone were determined by stereomicroscopic evaluation. Mandibles were undergone histological evaluation. Matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, bone morphogenetic protein (BMP)-2 expressions, tartrateresistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and inflammatory cell counts were determined.

Results:

The highest alveolar bone loss was observed in the periodontitis group. Both doses of gallic acid decreased alveolar bone loss as compared to the P group. TRAP-positive osteoclast cell counts were higher in the P group, and gallic acid successfully lowered these counts. Osteoblast cells also increased in gallic acid administered groups. Inflammation in the P group was also higher than those of C, G30, and G60 groups supporting the role of gallic acid in preventing inflammation. 30 and 60 mg/kg doses of gallic acid decreased MMP-8 levels and increased TIMP-1 levels. BMP levels increased in gallic acid administered groups, similar to several osteoblasts.

Conclusion:

Present results revealed an anti-inflammatory effect of gallic acid, which was indicated by decreased alveolar bone loss and collagenase activity and increased osteoblastic activity.
Assessment of Admission Time Cell Blood Count (CBC) Parameters in Predicting Post-primary Percutaneous Coronary Intervention TIMI Frame Count in Patients with ST-segment Elevation Myocardial Infarction
Authors: Vakili Hossein , Khaheshi Isa , Sharifi Amirsina , Nickdoost Negin , Namazi Mohammad H. , Safi Morteza , Saadat Habibollah , Parsa Saeed A. , Akbarzadeh Mohammad A. , Naderian Mohammadreza , Yousefi Negin , Shirazi Mahin , Tabary Mohammadreza
Published: February 2020

Objectives:

In this study, we aimed to assess the value of admission time CBC parameters in predicting post-primary PCI corrected TIMI frame count.

Background:

Recent years have witnessed a large series of studies evaluating different laboratory variables to predict no-reflow phenomenon following primary PCI (PPCI) in patients with STEMI. However, a general agreement about the most reliable predictor of the no-reflow phenomenon is challenging and also intriguing.

Methods:

The current study concluded 208 consecutive patients who underwent primary PCI for ST-Elevation Myocardial Infarction (STEMI) from January 2014 to February 2016. Blood samples were obtained after taking ECG. Complete blood samples were collected and analyzed within 5 minutes from sampling. Post-PCI corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was determined by one interventional cardiologist blinded to patients’ clinical data. The correlation between admission time blood parameters and post-primary PCI corrected TIMI frame count in patients with STEMI were assessed.

Results:

Corrected TIMI frame count was positively correlated with WBC count (R: 0.18, P-value: <0.01), neutrophil count (R: 0.34, P-value: <0.01), and platelet count (R: 0.23, P-value: <0.01) and negatively correlated with lymphocyte count (R: -0.2, P-value: <0.01). Multiple linear regression results demonstrated that corrected TIMI frame count was positively correlated with neutrophil count (P < 0·001) and platelet count (P < 0·001) and negatively correlated with lymphocyte count (p=0.004).

Conclusion:

High counts of WBC, neutrophil, and platelet and low count of lymphocyte may be predictors of no-reflow in STEMI patients undergoing PPCI. The clinical significance of such predictive parameters becomes clear as we consider the treatment approach in STEMI patients. Appropriate risk stratification leads to better treatment planning and allocation of resources.
Bioprocess Optimization for Enhanced Production of L-asparaginase via Two Model-Based Experimental Designs by Alkaliphilic Streptomyces fradiae NEAE-82
Authors: Soliman Hoda M. , El-Naggar Noura El-A. , El-Ewasy Sara M.
Published: February 2020

Background:

L-asparaginase is one of the most widely used chemotherapeutic agents for the treatment of a variety of lymphoproliferative disorders and particularly acute lymphoblastic leukemia. Due to increased applications of L-asparaginase in several industrial fields including food processing and medical fields, its production needs to be increased to several folds.

Objective:

The aim was (i) to identify the significant factors which affect L-asparaginase production by Streptomyces fradiae NEAE-82 and (ii) to achieve higher production of L-asparaginase.

Methods:

Sixteen assigned factors and three dummy factors were screened using Plackett-Burman experimental design to determine the most important factors for the production of L-asparaginase by Streptomyces fradiae NEAE-82.

Results:

L-asparagine was determined to be the most significant positive independent factor (P-value 0.0092) affecting L-asparaginase production by Streptomyces fradiae NEAE-82 followed by pH and NaCl with significant P-values of 0.0133 and 0.0272; respectively. These factors were further optimized by Box-Behnken experimental design. The optimized fermentation conditions, which resulted in the maximum L-asparagine activity of 53.572 UmL-1 are g/L: dextrose 4, L-asparagine 15, KNO3 2, MgSO4.7H2O 0.5, K2HPO4 1, FeSO4.7H2O 0.02, NaCl 0.2, ZnSO4 0.01 and inoculum size 2 %, v/v for 7 days incubation at temperature 37°C, agitation speed 100 rpm, pH 8.5.

Conclusion:

A total of 3.41-fold increase in the production of L-asparaginase was achieved in the medium after statistical improvement (53.572 UmL-1) as compared to the unoptimized basal medium used prior to the application of Plackett-Burman (15.704 UmL-1).
Patient Attitudes Toward Mobile Device Use by Health Care Providers in the Emergency Department: Cross-Sectional Survey
Authors: Alameddine Mohamad , Tamim Hani , Hadid Dima , Cheaito Mohamad-Ali , Makki Maha , Maatouk Hadi , Hitti Eveline
Published: February 2020

Background

Health care provider usage of mobile devices is increasing globally; however, there is little understanding of patient perceptions on this behavior in a health care setting.

Objective

The aim of this study was to assess patients’ attitudes toward mobile device usage by health care providers in the emergency department and to identify predictors of these attitudes.

Methods

The study was carried out at the emergency department of a large academic tertiary care medical center in Lebanon. A cross-sectional survey design was adopted by administering a questionnaire to medically stable adult patients who presented to the emergency department with an emergency severity index of 3, 4, or 5 between January 2017 and March 2018. The questionnaire collected relevant patient demographic information and included questions related to their mobile device usage along with those evaluating attitudes for the use of mobile devices by health care providers with respect to six major domains: role in health care, distraction potential, impact on communication, empathy, privacy, and professionalism. The attitude toward mobile device usage by health care providers in the emergency department was the main outcome variable. A stepwise logistic regression model was used to assess the association between the outcome variable and the demographic and attitude-related independent variables.

Results

Among the 438 eligible patients, 338 patients responded to the questionnaire for a response rate of 70.0%. Overall, 313/338 (92.6%) respondents agreed that mobile devices improve health care delivery, whereas 132/338 (39.1%) respondents were opposed to their usage by health care providers in the emergency department (95% CI: 34.0-44.4). The majority (240/338, 71.0%) of patients agreed that mobile devices are a source of distraction to health care providers in the workplace. Females (odds ratio [OR]=1.67, 95% CI: 1.00-2.78) as well as all patients (OR=2.54, 95% CI 1.36-4.76) who believed that mobile devices were a source of distraction, reflecting a lack of professionalism (OR=2.77, 95% CI 1.59-4.82) and impacting the provider’s ability to relate to the patient (OR=2.93, 95% CI 1.72-4.99), were more likely to agree that mobile devices should not be used in the emergency department.

Conclusions

Patients’ negative attitude toward mobile device use in the emergency department is largely driven by patient gender (females), patient perception of the distraction potential of the devices, and their negative impact on the health care provider’s empathy and professionalism. The findings of this study shed light on the importance of encouraging stakeholders to impose a digital professionalism code of conduct for providers working in acute health care settings.
Patients’ Attitudes Toward an Online Patient Portal for Communicating Laboratory Test Results: Real-World Study Using the eHealth Impact Questionnaire
Authors: Talboom-Kamp Esther , Tossaint-Schoenmakers Rosian , Goedhart Annelijn , Versluis Anke , Kasteleyn Marise
Published: February 2020

Background

Communicating laboratory test results online has several advantages for patients, such as improving clinical efficiency and accessibility, thereby helping patients to take an active role in managing their health.

Objective

This study aimed to investigate the experiences and self-efficacy of patients using an online patient portal that communicates laboratory test results.

Methods

We used the online-administered eHealth Impact Questionnaire to explore patients’ attitudes toward the portal. Patients visiting the portal were asked to complete the questionnaire. The subscale Information and Presentation assessed the usability of the patient portal and the subscale Motivation and Confidence to Act assessed self-efficacy to determine whether patients were motivated to act on the presented information. We used a cutoff score of 65 or greater to determine whether the portal was rated positively.

Results

The questionnaire was completed by 354 of 13,907 patients who viewed their laboratory results in the patient portal, with a response rate of 2.55%. The mean Information and Presentation score was 67.70 (SD 13.12) and the mean Motivation and Confidence to Act score was 63.59 (SD 16.22). We found a positive, significant correlation between the 2 subscales (r345=.77, P<.001).

Conclusions

Patients participating in the study rated the usability of the portal positively. However, the portal only slightly helped patients to take an active role in managing their own health. The low response rate precludes generalization of the results. Future research should examine avenues to further increase patients’ self-efficacy and study whether portal acceptability differs in subgroups. Patient portals conveying laboratory test results in understandable language seem usable and potentially provide a viable way to help patients take a more active role in managing their own health.
Prognostic significance of serum neurofilament light chain in acute ischemic stroke: a retrospective cohort study (Preprint)
Authors: Mao Zhongchen , Fu Zhixin , Zhang Jinhua , Zhao Yan , Sun Yong , Chen Kajia
Published: February 2020

BACKGROUND

Acute ischemic stroke affects a large number of people each year around the world. However, accurately predicting clinical outcome is still difficult.

OBJECTIVE

The aim of this cohort study was to explore the relationship between serum neurofilament light (NfL) concentration and clinical outcomes in these patients.

METHODS

A total of 820 patients with acute ischemic stroke were retrospectively enrolled between January 2012 and June 2017. Changes in patients' conditions, imaging data and other necessary information were obtained from their medical records. Blood samples were collected several times during the first two weeks of admission. Serum NfL levels were measured using a commercial Simoa NfL assay. In 6-month follow-up period, daily activity and cognitive function were assessed using modified Rankin Scale and Mini-mental State Examination.

RESULTS

Serum NfL levels gradually increased after the disease onset and peaked on the 7th day of admission. The elevated levels of peak NfL were roughly associated with the increased risk of poor daily activity function (OR: 2.92, 95%CI: 1.66 - 5.13), poor cognitive function (OR: 1.54, 95%CI: 1.03 - 2.29; OR: 1.66, 95%CI: 1.11 - 2.47; OR: 1.55, 95%CI: 1.03 - 2.37) and greater cognitive decline during the follow-up period (OR: 2.38, 95%CI: 1.07 - 5.26; OR: 1.99, 95%CI: 1.01 - 3.97). However, baseline serum NfL levels did not have similar prognostic significance.

CONCLUSIONS

Elevated peak concentration of NfL in serum predicts poor daily activity performance and cognitive function decline, and might be a prognostic biomarker for acute ischemic stroke.

CLINICALTRIAL

None.
A Smartphone Remote Monitoring App to Follow Up Colorectal Cancer Survivors: Requirement Analysis (Preprint)
Authors: Ayyoubzadeh Seyed Mohammad , Shirkhoda Mohammad , R Niakan Kalhori Sharareh , Mohammadzadeh Niloofar , Zakerabasali Somayyeh
Published: February 2020

BACKGROUND

Colorectal cancer survivors face multiple challenges after discharge. eHealth may potentially support them by providing tools such as smartphone apps. They have lots of capabilities to exchange information and could be used for remote monitoring of these patients.

OBJECTIVE

In this study, we addressed the required features for apps designed to follow up colorectal cancer patients based on survivors’ and clinical experts’ views.

METHODS

A mixed methods study was conducted. Features of related apps were extracted through the literature; the features were categorized, and then, they were modified. A questionnaire was designed containing the features listed and prioritized based on the MoSCoW (Must have, Should have, Could have, Won’t have) technique and an open question for each category. The link to the questionnaire was shared among clinical experts in Iran. The answers were analyzed using the content validity ratio (CVR), and based on the value of this measure, the minimum feature set of a monitoring app to follow up patients with colorectal cancer was addressed. In addition, a telephone interview with colorectal cancer survivors was conducted to collect their viewpoints regarding a remote monitoring system for colorectal cancer cases.

RESULTS

The questionnaire contained 10 sections evaluating 9 categories of features. The questionnaire was completed by 18 experts. The minimum set of features in the app was identified as patient information registration, sign and symptom monitoring, education, reminders, and patient evaluation (0.42 < CVR < 0.85). Features including physical activity, personalized advice, and social network did not achieve the minimum score (–0.11 < CVR < 0.39). We interviewed 9 colorectal cancer survivors. Information registration, sign and symptom monitoring, education, and personalized advice were the features with high priority from the survivors’ perspectives. Scheduling, shopping, and financial support features were emphasized by survivors in the interview.

CONCLUSIONS

The requirement set could be used to design an app for the targeted population or patients affected by other cancers. As the views from both survivors and clinical experts were considered in this study, the remote system may more adequately fulfill the need for follow-up of survivors. This eases the patients’ and health care providers’ communication and interaction.
Including Social and Behavioral Determinants in Predictive Models: Trends, Challenges, and Opportunities (Preprint)
Authors: Tan Marissa , Hatef Elham , Taghipour Delaram , Vyas Kinjel , Kharrazi Hadi , Gottlieb Laura , Weiner Jonathan
Published: February 2020

UNSTRUCTURED

In an era of accelerated health information technology capability, health care organizations increasingly use digital data to predict outcomes such as emergency department use, hospitalizations, and health care costs. This trend occurs alongside a growing recognition that social and behavioral determinants of health (SBDH) influence health and medical care use. Consequently, health providers and insurers are starting to incorporate new SBDH data sources into a wide range of health care prediction models, although existing models that use SBDH variables have not been shown to improve health care predictions more than models that use exclusively clinical variables. In this viewpoint, we review the rationale behind the push to integrate SBDH data into health care predictive models and explore the technical, strategic, and ethical challenges faced as this process unfolds across the United States. We also offer several recommendations to overcome these challenges to reach the promise of SBDH predictive analytics to improve health and reduce health care disparities.
Assessment of the Robustness of Convolutional Neural Networks in Labeling Noise by Using Chest X-Ray Images From Multiple Centers (Preprint)
Authors: Jang Ryoungwoo , Kim Namkug , Jang Miso , Lee Kyung Hwa , Lee Sang Min , Lee Kyung Hee , Noh Han Na , Seo Joon Beom
Published: February 2020

BACKGROUND

Computer-aided diagnosis on chest x-ray images using deep learning is a widely studied modality in medicine. Many studies are based on public datasets, such as the National Institutes of Health (NIH) dataset and the Stanford CheXpert dataset. However, these datasets are preprocessed by classical natural language processing, which may cause a certain extent of label errors.

OBJECTIVE

This study aimed to investigate the robustness of deep convolutional neural networks (CNNs) for binary classification of posteroanterior chest x-ray through random incorrect labeling.

METHODS

We trained and validated the CNN architecture with different noise levels of labels in 3 datasets, namely, Asan Medical Center-Seoul National University Bundang Hospital (AMC-SNUBH), NIH, and CheXpert, and tested the models with each test set. Diseases of each chest x-ray in our dataset were confirmed by a thoracic radiologist using computed tomography (CT). Receiver operating characteristic (ROC) and area under the curve (AUC) were evaluated in each test. Randomly chosen chest x-rays of public datasets were evaluated by 3 physicians and 1 thoracic radiologist.

RESULTS

In comparison with the public datasets of NIH and CheXpert, where AUCs did not significantly drop to 16%, the AUC of the AMC-SNUBH dataset significantly decreased from 2% label noise. Evaluation of the public datasets by 3 physicians and 1 thoracic radiologist showed an accuracy of 65%-80%.

CONCLUSIONS

The deep learning–based computer-aided diagnosis model is sensitive to label noise, and computer-aided diagnosis with inaccurate labels is not credible. Furthermore, open datasets such as NIH and CheXpert need to be distilled before being used for deep learning–based computer-aided diagnosis.
“I Like the Idea of It…But Probably Wouldn’t Use It” - Health Care Provider Perspectives on Heart Failure mHealth: Qualitative Study (Preprint)
Authors: Portz Jennifer Dickman , Ford Kelsey Lynett , Elsbernd Kira , Knoepke Christopher E , Flint Kelsey , Bekelman David B , Boxer Rebecca S , Bull Sheana
Published: February 2020

BACKGROUND

Many mobile health (mHealth) technologies exist for patients with heart failure (HF). However, HF mhealth lacks evidence of efficacy, caregiver involvement, and clinically useful real-time data.

OBJECTIVE

We aim to capture health care providers’ perceived value of HF mHealth, particularly for pairing patient–caregiver-generated data with clinical intervention to inform the design of future HF mHealth.

METHODS

This study is a subanalysis of a larger qualitative study based on interviewing patients with HF, their caregivers, and health care providers. This analysis included interviews with health care providers (N=20), focusing on their perceived usefulness of HF mHealth tools and interventions.

RESULTS

A total of 5 themes emerged: (1) bio-psychosocial-spiritual monitoring, (2) use of sensors, (3) interoperability, (4) data sharing, and (5) usefulness of patient-reported outcomes in practice. Providers remain interested in mHealth technologies for HF patients and their caregivers. However, providers report being unconvinced of the clinical usefulness of robust real-time patient-reported outcomes.

CONCLUSIONS

The use of assessments, sensors, and real-time data collection could provide value in patient care. Future research must continually explore how to maximize the utility of mHealth for HF patients, their caregivers, and health care providers.
MI-PACE Home-Based Cardiac Telerehabilitation Program for Heart Attack Survivors: Usability Study (Preprint)
Authors: Ding Eric Y , Erskine Nathaniel , Stut Wim , McManus David D , Peterson Amy , Wang Ziyue , Escobar Valle Jorge , Albuquerque Daniella , Alonso Alvaro , Botkin Naomi F , Pack Quinn R , McManus David D
Published: February 2020

BACKGROUND

Cardiac rehabilitation programs, consisting of exercise training and disease management interventions, reduce morbidity and mortality after acute myocardial infarction.

OBJECTIVE

In this pilot study, we aimed to developed and assess the feasibility of delivering a health watch–informed 12-week cardiac telerehabilitation program to acute myocardial infarction survivors who declined to participate in center-based cardiac rehabilitation.

METHODS

We enrolled patients hospitalized after acute myocardial infarction at an academic medical center who were eligible for but declined to participate in center-based cardiac rehabilitation. Each participant underwent a baseline exercise stress test. Participants received a health watch, which monitored heart rate and physical activity, and a tablet computer with an app that displayed progress toward accomplishing weekly walking and exercise goals. Results were transmitted to a cardiac rehabilitation nurse via a secure connection. For 12 weeks, participants exercised at home and also participated in weekly phone counseling sessions with the nurse, who provided personalized cardiac rehabilitation solutions and standard cardiac rehabilitation education. We assessed usability of the system, adherence to weekly exercise and walking goals, counseling session attendance, and disease-specific quality of life.

RESULTS

Of 18 participants (age: mean 59 years, SD 7) who completed the 12-week telerehabilitation program, 6 (33%) were women, and 6 (33%) had ST-elevation myocardial infarction. Participants wore the health watch for a median of 12.7 hours (IQR 11.1, 13.8) per day and completed a median of 86% of exercise goals. Participants, on average, walked 121 minutes per week (SD 175) and spent 189 minutes per week (SD 210) in their target exercise heart rate zone. Overall, participants found the system to be highly usable (System Usability Scale score: median 83, IQR 65, 100).

CONCLUSIONS

This pilot study established the feasibility of delivering cardiac telerehabilitation at home to acute myocardial infarction survivors via a health watch–based program and telephone counseling sessions. Usability and adherence to health watch use, exercise recommendations, and counseling sessions were high. Further studies are warranted to compare patient outcomes and health care resource utilization between center-based rehabilitation and telerehabilitation.
P2P Communication among Computers and Smartphones Based on Bluetooth and Wi-Fi Direct Technologies
Authors: Uzayisenga Venant , Priyambodo Tri Kuntoro
Published: February 2020

As result of the development of technology, most of modern computer and smartphones are Bluetooth and Wi-Fi direct wireless technologies enabled. While those wireless technologies come with the benefits of interconnecting devices without the need access point or central base station. However, computer and smartphones connected via Bluetooth based or via Wi-Fi Direct connection does not guarantee intercommunication or data transmission in meaningful way. Therefore, third party software is always needed to help for achieving data transmission. In this research an effort is done to design and develop P2P software applications and web based application by using C# and ASP.net MVC programming languages as features of Visual Studio 2017. Application would facilitate P2P communication of interconnected devices via the same channel. Built software system has been tested based on functional testing method, and usability testing. The result from functional testing shows that P2P communication meets functional requirements while usability testing has an average score of 72.2% from System Usability Scale method. The results from SUS scores brands our proposed P2P communication system to be good and highly accepted.
Combination of AHP Method and VIKOR Method For Assesing Sunday School Teacher
Authors: Waas Devi Valentino , Suprapto Suprapto
Published: February 2020

The performance appraisal of Sunday school teacher in the Imanuel Lurang congregation aims to measure and distinguish the quality of performance achieved by Sunday school teacher and decide various policies such as giving rewards to every Sunday school teacher with the best performance, and for Sunday school teacher who have poor performance scores will be given a guiding, approach, etc. The number of criteria in determining the quality of Sunday school teacher is not an easy thing to do by manual. Then it is essential that a computerized performance appraisal-based performance  app can speed up the process of progressing to be more effective and efficient. This research develops decision support systems (DSS) that is dynamic using the PHP programming language, by combining the AHP method that has been refined by the VIKOR method. The AHP method is used in determining the weight of each criterion, and the VIKOR method is used for the ranking process. Test results indicate that the system can provide a sequence of alternative Sunday school teacher that will be used as recommendations for decision makers to determine which Sunday school teachers are quality and not qualified.