bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare-Associated Infections Due to Multidrug-Resistant Organisms: a Surveillance Study on Extra Hospital Stay and Direct Costs
Authors: Giraldi Guglielmo , Montesano Marzietta , Napoli Christian , Frati Paola , La Russa Raffaele , Santurro Alessandro , Scopetti Matteo , Orsi Giovanni B. 
Published: April 2019

Background:
The increasing antimicrobial resistance poses a challenge to surveillance systems
and raises concerns about the impact of multidrug-resistant organisms on patient safety.

Objective:
The study aimed to estimate extra hospital stay and economic burden of infections due to alert
organisms - mostly multidrug-resistant - in a teaching hospital.

Methods:
The present retrospective matched cohort study was conducted based on the analysis of hospital
admissions at Sant’Andrea Teaching Hospital in Rome from April to December 2015. Extra hospital
stay was the difference in the length of stay between each case and control. All the patients developing
an infection due to an alert organism were considered cases, all others were eligible as controls. The
costs of LOS were evaluated by multiplying the extra stay with the hospital daily cost.

Results:
Overall, 122 patients developed an infection due to alert organisms and were all matched with
controls. The attributable extra stay was of 2,291 days (mean 18.8; median 19.0) with a significantly increased
hospitalization in intensive care units (21.2 days), bloodstream infections (52.5 days), and infections
due to Gram-negative bacteria (mean 29.2 days; median 32.6 days). Applying the single day hospital
cost, the overall additional expenditure was 11,549 euro per patient. The average additional cost of
antibiotic drugs for the treatment of infections was about 1,200 euro per patient.

Conclusion:
The present study presents an accurate mapping of the clinical and economic impact of infections
attributable to alert organisms demonstrating that infections due to multidrug-resistant organisms
are associated with higher mortality, longer hospital stays, and increased costs.

Article Highlights Box:
The increasing antimicrobial resistance poses a challenge for surveillance
systems and raises concerns about the impact of multidrug-resistant organisms on patient safety.
• Healthcare-associated infections (HAIs) have historically been recognized as a significant public health
problem requiring close surveillance.
• Despite several and reliable findings have been achieved on clinical issues, our knowledge on the economic
impact of healthcare-associated infections due to multidrug-resistant organisms needs to be widened.
• Estimating the cost of infections due to multidrug-resistant organisms in terms of extra hospital stay
and economic burden is complex, and the financial impact varies across different health systems.
• Evaluations of social and economic implications of hospital infections play an increasingly important
role in the implementation of surveillance systems.
• The costs of infection prevention and control programs and dedicated personnel are relatively low and
self-sustainable when efficient.
Pharmacological Management of Diabetic Nephropathy
Authors: Papademetriou Vasilios , Alataki Sofia , Stavropoulos Konstantinos , Papadopoulos Christodoulos , Bakogiannis Kostas , Tsioufis Kostas 
Published: April 2019

Introduction:Diabetes mellitus (DM) is one of the most common diseases worldwide. Its adverse effects on several body organs, have made treatment of DM a priority. One of the most serious complications of DM is diabetic nephropathy (DN).Objective:The aim of this review is to critically discuss available data on the pharmacological management of DN.Objective:A comprehensive review of the literature was performed to identify studies assessing the impact of several drug classes on DN.Results:Several studies have been conducted in order to find a novel and effective treatment of DN. So far, the cornerstone therapy of DN consists of renin-angiotensin system (RAS) inhibitors, agents that decrease the synthesis of intrarenal angiotensin II or block its receptors. Their antiproteinuric and antihypertensive effects can not only decelerate the progress of DN but prevent its onset as well. Novel antidiabetic drugs, such as sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide- 1 receptor agonists (GLP-1 RA), are promising agents in the therapy of DN, due to their positive effect on renal and cardiovascular adverse events. From lipid-lowering agents, atorvastatin improves DN up to stage 3 and substantially reduces CVD.Conclusion:RAS inhibitors, SGLT-2i and GLP-1 agonists were found to be beneficial for the treatment of DN. Larger renal trials are needed in order to incorporate these drugs into the first line treatment of DN.
The Incidence of Adverse Drug Reactions in Patients Treated with Statins in the Emirates: A Retrospective Cohort Study
Authors: Shehab Abdulla , Bhagavathula Akshaya S. , Elnour Asim A. , Al-Rasadi Khalid , Al-Shamsi Saif 
Published: April 2019

Aim:
We investigated the incidence of adverse drug reactions (ADRs) in patients treated with
statins for cardiovascular (CV) risk among the United Arab Emirates (UAE) population.

Methods:
This is a retrospective cohort study conducted among statin users attending 2 tertiary care
centres: Al Ain and Tawam hospitals in Al Ain city, UAE. We retrieved the clinical profile of all the
patients taking statins from January 2011 to January 2015 using our electronic database (Cerner®).

Results:
Among 556 patients (418 men; 138 women) taking statins, 237 ADRs were reported (186 men;
51 women). The incidence of ADRs was 40.7%, and was more frequent among patients at “high CV
disease (CVD) risk” and “moderate CVD risk” than other risk categories. High CVD risk (odds ratio,
1.67; 95% confidence interval [CI], 1.19-2.34), vitamin D deficiency 1.45 (95% CI, 0.89-2.38), type 2
diabetes 1.22 (95% CI, 0.84-1.77) and hypertension 1.13 (95% CI, 0.70-1.83) are some of the factors
that were associated with statin ADRs.

Conclusion:
The incidence of ADRs among statin users was 42.6%, and frequent ADRs (49%) were
noted in patients with high CVD risk. Early identification of these ADRs should improve patient adherence
to life-saving statin treatment.
Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as Immunosuppressants
Authors: Minhas Richa , Bansal Gulshan , Bansal Yogita 
Published: April 2019

Introduction:
Nitric oxide (NO) is an important mediator in the pathogenesis and control
of immune system-related disorders and its levels are modulated by inducible NO synthase
(iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders.
The present study aims at the development of coupled molecules via selection of pharmacophores
for both immunomodulatory and antioxidant activities through iNOS inhibition.

Methods:
Variedly substituted coumarin moieties are coupled with naturally occurring phenols
through an amide linkage and were predicted for activities using computer-based program PASS.
The compounds predicted to have dual activities were synthesized. Docking studies were carried
out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory
and antioxidant activities.

Results:
The synthesized compounds were found to be pure and were obtained in good yields.
Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for
evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of
NBT dye and showed maximum % iNOS inhibition. In DPPH assay, compound YR4e was observed
as the most potent antioxidant (EC50 0.33 µM/mL). Based on these studies, compounds
YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the
most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and
lower HAT value of 3.5.

Conclusion:
Compound YR2e can be utilized as a pharmacological agent in the prevention or
treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis,
organ transplant and other autoimmune disorders.
PCR: An Effective, Faster and Relevant Method for the Detection of Clinical Isolates of Candida albicans
Authors: Zaidi Kamal Uddin , Mani Abin , Parmar Richa , Thawani Vijay 
Published: April 2019

Background:
Candida albicans is associated with infectious diseases with colonization,
in both immunocompromised and immunocompetent patients. Antibiotic treatment can develop
candidiasis.

Objective:
Evaluation of ITS 4 and ITS5 primer expression on clinical isolates of C. albicans.

Methods:
Fifty clinical isolates of C. albicans were collected from different sites viz. Catheter Tip
(CT), High Vaginal Swab (HVS) and Urine (U).

Results:
Using the universal fungal primers ITS4 and ITS5, PCR produced a single monomorphic
amplification at 520 bp indicating that the strains are of same genetic identity.

Conclusion:
This is an effective, faster and relevant method for the detection and characterization
of clinically isolated strains of C. albicans.
HS-MMGKG: A Fast Multi-objective Harmony Search Algorithm for Two-locus Model Detection in GWAS
Authors: Sun Liyan , Liu Guixia , Su Lingtao , Wang Rongquan 
Published: April 2019

Background::
Genome-Wide Association Study (GWAS) plays a very important role in
identifying the causes of a disease. Because most of the existing methods for genetic-interaction
detection in GWAS are designed for a single-correlation model, their performances vary
considerably for different disease models. These methods usually have high computation cost and
low accuracy.

Method::
We present a new multi-objective heuristic optimization methodology named HSMMGKG
for detecting genetic interactions. In HS-MMGKG, we use harmony search with five
objective functions to improve the efficiency and accuracy. A new strategy based on p-value and
MDR is adopted to generate more reasonable results. The Boolean representation in BOOST is
modified to calculate the five functions rapidly. These strategies take less time complexity and
have higher accuracy while detecting the potential models.

Results::
We compared HS-MMGKG with CSE, MACOED and FHSA-SED using 26 simulated
datasets. The experimental results demonstrate that our method outperforms others in accuracy and
computation time. Our method has identified many two-locus SNP combinations that are
associated with seven diseases in WTCCC dataset. Some of the SNPs have direct evidence in CTD
database. The results may be helpful to further explain the pathogenesis.

Conclusion::
It is anticipated that our proposed algorithm could be used in GWAS which is helpful
in understanding disease mechanism, diagnosis and prognosis.
Synthesis of New Dihydroquinopimaric Acid Analogs with Nitrile Groups as Apoptosis-Inducing Anticancer Agents
Authors: Tretyakova Elena V. , Salimova Elena V. , Parfenova Lyudmila V. , Yunusbaeva Milyausha M. , Dzhemileva Lilya U. , D’yakonov Vladimir A. , Dzhemilev Usein M. 
Published: April 2019

Background:
Cyan-containing compounds are of great interest as potential anticancer agents. Terpenoids
can severe as a natural matrix for the development of promising derivatives with antitumor activity.

Methods:
The 2-cyanoethoxy methyl dihydroquinopimarate derivatives (5-9) were synthesized by the reaction of
the intermediates (1-4) with acrylonitrile in the presence of alkali (30% KOH solution) using triethylbenzylammonium
chloride. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI) Protocol,
while apoptosis was studied by flow cytometric analysis of Annexin V and 7-aminoactinomycin D staining and
cell cycle was analyzed using the method of propidium iodide staining.

Results:
Synthesis of new dihydroquinopimaric acid derivatives with nitrile groups was carried out. The obtained
cyanoethyl derivatives were converted into tetrazole, amine, oxadiazole and amidoxime analogs. The primary
screening for antitumor activity showed the highest cytotoxic potency of the cyanoethyl-substituted compounds.
The introduction of cyanoethyl groups at C-1, C-4 and C-1, C-4, C-20 positions of dihydroquinopimaric acid
methyl ester provided antiproliferative effect towards the Jurkat, K562, U937, and HeLa tumor cell cultures
(CC50=0.045-0.154µM). These nitrile derivatives are effective inducers of tumor cell apoptosis affecting the S and
G2 phases of the cell cycle in a dose-dependent manner.

Conclusion:
The cyanoethyl analogs of dihydroquinopimaric acid reported herein are apoptosis inducers and cytotoxic
agents. These findings will be useful for the further design of more potent cytotoxic agents based on natural
terpenes.
The Possibility of Preventive and Therapeutic Use of Green Tea Catechins in Prostate Cancer
Authors: Rogovskii Vladimir S. , Popov Sergey V. , Sturov Nikolai V. , Shimanovskii Nikolai L. 
Published: April 2019

Background:Prostate cancer is one of the most frequent types of cancer. Despite the existence of various treatment strategies, treatment of prostate cancer still presents serious difficulties (especially in advanced stages). Polyphenols have been extensively assessed in terms of their potential use for prostate cancer treatment and prevention. Catechins are among the most well-known polyphenols in this respect.Objective:In this review, we summarize clinical study results concerning catechin applications with regard to prostate cancer treatment and prevention. We discuss some of the main mechanisms of the anticarcinogenic action of catechins.Conclusion:The main mechanisms of the anticarcinogenic action of catechins are subdivided into two major types: (i) direct action on cancer cells and (ii) indirect effect based on catechins’s impact on the microenvironment of cancer cells, particularly in relation to the immune system. At this level catechins might reduce tumor-associated inflammation and immune tolerance.
Evaluation of Antitumor Activity and Hepatoprotective Effect of Mitomycin C Solubilized in Chamomile Oil Nanoemulsion
Authors: Al-Otaibi Waad A. , Alkhatib Mayson H. , Wali Abdulwahab N. 
Published: April 2019

:The present study aimed to investigate the antitumor activity and hepatoprotective effect of the MTC, when combined with CHAM oil nanoemulsion (NE), (CHAM-MTC) on the tumor growth.Materials/Methods:The in vitro study assessed the antineoplastic effect of CHAM-MTC on the MCF-7 breast cancer cells while the in vivo therapeutic effectiveness and toxicities of CHAM-MTC were evaluated in Ehrlich Ascites Carcinoma (EAC) bearing mice. One hundred female Swiss albino mice, divided equally into non-EAC group (negative control), untreated EAC group (positive control) and three EAC groups received once intraperitoneal injection of 0.2ml CHAM-NE, 0.2ml Normal Saline (NS) contained MTC (1mg/kg) and 0.2ml CHAM-NE mixed with MTC (1mg/kg), respectively.Results:The in vitro results indicated that CHAM-NE could potentiate the effect of MTC in sub-effective concentrations since the half-maximal inhibitory concentration (IC50) was reduced by a factor of 21.94 when compared to the MTC-NS. The in vivo study revealed that mice treated with CHAM-MTC showed a significant increase in the median survival time (MST= 37 days) when compared to the MTC-NS treated group (MST= 29.50 days). In addition, CHAM-MTC showed protective ability against the oxidative stress and hepatic damage induced by EAC and MTC treatment.Conclusion:The combination of MTC with CHAM-NE could be valuable in enhancing the therapeutic efficacy of MTC against EAC and in eliminating MTC-induced hepatotoxicity.
Novel Curcumin Inspired Antineoplastic 1-Sulfonyl-4-Piperidones: Design, Synthesis and Molecular Modeling Studies
Authors: Fawzy Nehmedo G. , Panda Siva S. , Fayad Walid , El-Manawaty May A. , Srour Aladdin M. , Girgis Adel S. 
Published: April 2019

Background:
Curcumin is a well-known example of plant origin exhibiting promising diverse biological
properties such as, anti-inflammatory and antitumor as well as poor pharmacokinetic/pharmacodynamic
properties. This is why effective agents based on its chemical scaffold were explored.

Methods:
A set of 3,5-bis(ylidene)-1-(alkylsulfonyl)piperidin-4-ones were synthesized in excellent yield (80-
96%) through dehydrohalogenation reaction of 3,5-bis(ylidene)-4-piperidinones with the corresponding alkane
sulfonyl chloride in the presence of triethylamine. Antiproliferative properties of the synthesized compounds
(dienone/curcumin inspired analogues) were studied by the standard MTT technique.

Results:
Most of the synthesized compounds revealed antiproliferative properties against HCT116 (colon) and
A431 (skin/squamous) cancer cell lines with IC50 values at sub-micromolar level. Compound 36 also exhibited
potency against MCF7 (breast) and A549 (lung) cancer cell lines (IC50 = 2.23, 4.27µM, respectively) higher than
that of the reference standards (IC50 = 3.15, 5.93µM for 5-fluorouracil and doxorubicin against MCF7 and A549
cell lines, respectively). Cytotoxic properties of the synthesized compounds against non-cancer RPE1 cell line
supported the safety profile of the effective agents against normal cells. Molecular modeling (3Dpharmacophore
and 2D-QSAR) studies validated the observed bio-properties and explained the parameters
governing activity. Inhibitory properties of compounds 27 and 29 (representative examples of the promising
antiproliferative agents synthesized) supported their mode of action against topoisomerase IIα

Conclusion:
The synthesized scaffold is a promising antitumor agent (with special selectivity against colon and
skin/squamous cancer cell lines) so, it can be considered for further investigation and development of highly
effective hits/leads based on the computational models obtained.
Dual Anti-cancer and Anti-Itch Activity of PD176252 Analogues: Design, Synthesis and Biological Evaluation
Authors: Yu Ming-Jun , Yao Sen , Li Ting-Ting , Yang Rui , Yao Ri-Sheng 
Published: April 2019

Background:Cancer patients treated with targeted anti-cancer drug suffer from itch or pruritus. Itch or pruritus is an unpleasant sensation that brings about a negative impact on quality of life, and serious itch may lead to dose reduction and even discontinuation. Gastrin releasing peptide receptor (GRPR) plays a critical role in itch, inflammation and cancer, and GRPR antagonist has obvious effect on cancer, inflammation and itch. The aim of this paper is to develop a new agent with anti-cancer and anti-itch activity.Methods:A series of GRPR antagonist PD176252 analogues (3a-3l) were designed and synthesized. Both anticancer and anti-itch activities were evaluated. Anti-cancer activity was evaluated in three human cancer cell lines in vitro, the anti-itch activity in evaluated with Kunming mice by intrathecal injection of chloroquine phosphate as a modeling medium. And the cytotoxicity on normal cells was evaluated.Results:Of the tested compounds, compound 3i showed potently anti-cancer activity to all cancer cell lines tested with IC50 values of 10.5µM (lung), 11.6µM (breast) and 12.8µM (liver) respectively and it also showed significant inhibition of the scratching behavior. Comparing with PD17625, compound 3i and 3g gave better inhibition activities against all cancer cell lines, compound 3b, 3c and 3i showed better anti-itch activity. The compound 3i is safe for normal breast and liver normal cells, but it has high cytotoxicity on normal lung cell.Conclusion:The synthesized compounds have dual anti-cancer and anti-itch activity, so the development of drug with dual anti-tumor and anti-itch property is possible.
SIMULATION OF A DEFECTLESS LIFECYCLE OF UNIQUE UNDERGROUND STRUCTURES OF THE SEWAGE SYSTEM AT THE STAGE OF THEIR CONSTRUCTION IN DIFFICULT SOIL CONDITIONS
Authors: Perminov Nickolai 
Published: April 2019

Emperor Alexander I Saint-Petersburg State Transport University, Saint-Petersburg, RUSSIA
Abstract: Simulation of the parameters of a defectless lifecycle of large caissons at the stage of their plunging into heterogeneous soil milieu allows considerable expansion of the area of rational use of underground areas of megacities for deep transport facilities and engineering infrastructure due to provision of structural safety and sustainable operation of a special underground structure. Mega sizes of an RC caisson allow creating open underground areas, unique in volumes and deepness. The analysis of behavior of a massive gravitational fencing caisson at its incrementing and plunging into heterogenenous soil milieu allowed identifying the nature of its non-linear and unsteady behavior. Unsteadiness of the processes of interaction of a large structure and soil milieu accompanied by geometrical changeability causes the necessity to create methods of adaptive control of strain- stress behavior of the system “gravitational large body - heterogeneous host medium” for decreasing aggravating influence of these effects on strength, deformability and reliability of the structure at the subsequent stages of its lifecycle. Due to joint step-by-step implementation of geotechnical and structural calculations a history of the processes of caisson-soil milieu interaction is modeled and the parameters of adaptive control of strain-stress behavior are predicted, thus providing conditions of controlled lowering. The paper demonstrates results of consistent implementation of the given concept at the lifecycle stages of the unique caissons for the sewage system of the megacity beginning from numerical modeling during design to computer models of control of strain-stress behavior of the system “large caisson - soil bulk” using the methods of geotechnology with subsequent monitoring provision of the defectless stage of construction.
Elevated Serum Uric Acid Is Associated With Greater Risk for Hypertension and Diabetic Kidney Diseases in Obese Adolescents With Type 2 Diabetes: An Observational Analysis From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study
Authors: Bjornstad Petter , Laffel Lori , Lynch Jane , El ghormli Laure , Weinstock Ruth S. , Tollefsen Sherida E. , Nadeau Kristen J. ,   for the TODAY Study Group
Published: April 2019

OBJECTIVE
Elevated serum uric acid (SUA) is increasingly recognized as a risk factor for kidney disease in adults with diabetes, but data in youth are limited. We hypothesized that elevated SUA predicts development of elevated urinary albumin excretion (UAE) and hypertension over time in teens with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS
Serum creatinine, cystatin C, SUA, and the urine albumin-to-creatinine ratio (UACR) were assessed in 539 obese youth, ages 12–17 years, with T2D duration &lt;2 years at baseline in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and cystatin C. Hypertension was defined as systolic or diastolic blood pressure ≥130/80 mmHg and elevated UAE as UACR ≥30 mg/g. Cox proportional hazards models evaluated the relationship between SUA and outcome variables longitudinally over an average follow-up of 5.7 years, adjusting for age, sex, race/ethnicity, BMI, HbA1c, eGFR, ACE inhibitor/angiotensin receptor blocker use, and TODAY treatment group assignment.

RESULTS
At baseline, hyperuricemia (≥6.8 mg/dL) was present in 25.6% of participants, hypertension in 18.7%, and elevated UAE in 6.1%. During follow-up of up to 7 years, hypertension developed in 37.4% and UAE in 18.0%. Higher baseline SUA increased the risk of incident hypertension (hazard ratio [HR] 1.19, 95% CI 1.03–1.38, per 1 mg/dL increase in SUA) and elevated UAE (HR 1.24, 95% CI 1.03–1.48) in adjusted models.

CONCLUSIONS
Hyperuricemia was common in youth with T2D. Higher baseline SUA independently increased the risk for onset of hypertension and elevated UAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth.