bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Knee Arthroplasty in a Low-Income Country
Authors: Graham Simon Matthew , Moffat Chipiliro , Lubega Nicholas , Mkandawire Nyengo , Burgess David , Harrison William J.
Published: March 2018

Background:

We describe our 10-year experience with total knee arthroplasty in patients who are included in the Malawi National Joint Registry.

Methods:

A total of 127 patients underwent 153 total knee arthroplasties (TKAs) between 2005 and 2015. The mean duration of follow-up was 4 years and 3 months (range, 6 months to 10 years and 6 months). The study group included 98 women and 29 men with a mean age of 65.3 years (range, 24 to 84 years). Nine patients were human immunodeficiency virus (HIV)-positive.

Results:

The primary indication for surgery was osteoarthritis (150 knees), and the mean preoperative and postoperative Oxford Knee Scores were 16.81 (range, 4 to 36) and 45.61 (range, 29 to 48), respectively. Four knees (2.6%) were revised because of early periprosthetic joint infection (1 knee), aseptic loosening (1 knee), and late periprosthetic joint infection (2 knees). There were no perioperative deaths. In the group of 9 patients who were HIV-positive, there were no early or late complications and the mean Oxford Knee Score was 47 (range, 42 to 48) at the time of the latest follow-up.

Conclusions:

This study demonstrated good short-term results following 153 primary TKAs performed in a low-income country.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Prevalence of and Predictive Factors for Scoliosis After Surgery for Congenital Heart Disease in the First Year of Life
Authors: Kaito Takashi , Shimada Masatoshi , Ichikawa Hajime , Makino Takahiro , Takenaka Shota , Sakai Yusuke , Yoshikawa Hideki , Hoashi Takaya
Published: March 2018

Background:

The surgical treatment of congenital heart disease is reported to be associated with a high prevalence of scoliosis, although the detailed etiology is unknown. Surgical interventions involving the rib cage are considered to increase the risk of scoliosis. However, whether the cardiac condition or the procedure performed makes patients more susceptible to the development of spinal deformity is controversial.

Methods:

The present study included 483 patients who underwent surgery for the treatment of congenital heart disease with use of procedures involving the immature rib cage (sternotomy and/or thoracotomy) during the first year of life, followed by the evaluation of standing chest radiographs at ≥10 years of age. Patients with congenital spinal deformity and potential neuromuscular disease were excluded. The prevalence of and predictive factors for scoliosis were evaluated. The presence of scoliosis (Cobb angle ≥10° to <20°, ≥20° to <30°, ≥30° to <45°, ≥45°), the convex side of the curve, and the location of the curve were evaluated radiographically. Potential predictive factors that were analyzed included the age at the time of surgery, surgical approach, use of cardiopulmonary bypass, postoperative heart failure and/or cyanosis, New York Heart Association (NYHA) class, cardiomegaly, and age at the time of radiography.

Results:

The mean age at the time of surgery was 112 days, and the mean age at the time of radiography was 14.4 years. The prevalence of scoliosis was 42.4%, and the prevalences of ≥10° to <20°, ≥20° to <30°, ≥30° to <45°, and ≥45° scoliosis were 31.7%, 5.8%, 2.5%, and 2.5%, respectively. Three patients underwent surgery for the treatment of progressive scoliosis. Multivariate analysis indicated that the predictive factors were female sex, left thoracotomy, bilateral thoracotomy, NYHA class, and age at the time of radiography for ≥10° scoliosis; cardiomegaly, NYHA class, and age at the time of radiography for ≥20° scoliosis; cardiomegaly, number of surgical procedures, and age at the time of radiography for ≥30° scoliosis; and cardiomegaly for ≥45° scoliosis. Age at the time of radiography was a predictor of <45° scoliosis; however, the relative association was small.

Conclusions:

Surgery for the treatment of congenital heart disease during the first year of life was associated with a high prevalence of scoliosis (≥40%). While female sex was one of several predictors of ≥10° scoliosis, cardiomegaly was the sole predictor of ≥45° scoliosis.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Reliability, Validity and Turkish Adaptation of Self-Directed Learning Scale (SDLS)
Authors: Demircioğlu Zeynep İşıl , Öge Burak , Fuçular Emine Ezgi , Çevik Tuğçe , Denizci Nazlıgül Merve , Özçelik Erol
Published: March 2018

Self-Directed Learning Scale (SDLS) developed by Lounsbury, Levy, Park, Gibson, and Smith (2009) was used for determining individuals’ self-directed learning. The purpose of this study was to translate the SDLS
into Turkish and to investigate its reliability and validity with a sample of
272 university students. The SDLS, the Modified Schutte Emotional Intelligence Scale
(MSEIS), Self-Directed Learning Inventory (SDLI), and the Causal Uncertainty
Scale (CUS) for determining convergent validity was applied to the
participants. Factor analyses results verified the uni-dimensionality of the scale.
The test–retest correlation of SDLS was 0.82, whereas Cronbach alpha coefficient of the
scale was founded as 0.85 in the reliability analyses. Correlation coefficients
representing for convergent validities varied from -0.30 to 0.72 (p < .01) and criterion validity of
the scale was determined as 0.236 when cumulative GPA was used as criterion
in the assessment of concurrent validity. The findings suggest that the Turkish
adaptation of SDLS is a valid and reliable tool to measure self-directed
learning in Turkish samples.
Communal latrine utilization and associated factors in Addis Ababa, Ethiopia: a community-based cross-sectional study
Authors: Kefeni Elzabeth Girma , Yallew Walelegn Worku
Published: March 2018

Despite the quick urban population growth increased volume of wastes, including human excreta, which demands an expanded need of infrastructure, solid institutional setup and communities' engagement for management of safe disposal of excreta, arrangement of such basic social services has not developed as per the rate of population growth. Mostly, communal latrines are inclined towards an absence of cleanliness, as they accommodate many people beyond their capacity, filling up septic tanks quickly. A community-based cross-sectional study conducted in 817 randomly selected communal latrine user households, five focus group discussions and four key informant interviews were analysed. Bivariate and multivariate logistic regression analysis was performed to discover the impact of different factors on the use of communal latrines. The findings revealed that the rate of communal latrine use in Addis Ababa was about 79.8%. Unhygienic conditions, latrine emptying challenges, extreme smell, number of family units sharing the same squats, and latrine designs for the aged and children were identified as barriers to latrine utilization. This study suggests that, in parallel with the continued investments to increase access to sanitary facilities in the city, the management and behavioural change part has likewise to be stressed for better use and sustainability.
Chronic Kidney Disease and the Search for New Biomarkers for Early Diagnosis
Authors: Saucedo Alma L. , Perales-Quintana Marlene M. , Paniagua-Vega David , Sanchez-Martinez Concepcion , Cordero-Perez Paula , Minsky Noemi W.
Published: March 2018

Chronic kidney disease (CKD) is a progressive condition characterized by a permanent and
irreversible loss of renal function. In accordance to international guidelines, CKD clinical diagnosis
methods are based on creatinine and albumin levels and glomerular filtration rate. Unfortunately, these
parameters are scarcely affected in early stages, and its inherent intrinsic variability only allows for the
identification of intermediate and advanced stages, when life expectancy has become shorter and treatment
poses a significant financial investment. In this context, several targeted strategies have been designed
for searching novel markers. Among them, "omics" techniques have emerged, mainly based on
proteomics and metabolomics research. Urine and serum samples have been selected as starting material
to conduct the identification of new CKD biomarkers, capable of differentiating between stages and
predicting progression outcomes. In many cases, the principal objective is to develop a fast and reliable
clinical method for non-invasive analysis in the early progression stages of the disease. On the other
hand, significant efforts have been directed to identify molecules related to the CKD end stage in order
to adequate therapies, reduce impairments, and have a positive impact on survival rate. In this article,
the state of the art of novel proposed biomarkers for CKD identification is reviewed, with the aim of
underlining its molecular diversity, emphasizing chemical structure differences and correlating its biological
relevance. Efforts directed in this line could provide evidence of metabolic pathways imbalance,
and lead to the development of new integral strategies for CKD evaluation and management.
Linking Antimicrobial Potential of Natural Products Derived from Aquatic Organisms and Microbes Involved in Alzheimer’s Disease - A Review
Authors: Stojković Dejan , Kostić Marina , Smiljković Marija , Aleksić Milena , Vasiljević Perica , Nikolić Miloš , Soković Marina
Published: March 2018

The following review is oriented towards microbes linked to Alzheimer’s disease (AD) and antimicrobial
effect of compounds and extracts derived from aquatic organisms against specific bacteria,
fungi and viruses which were found previously in patients suffering from AD. Major group of microbes
linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis,
Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida
sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex
virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact,
this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes.
This literature review might serve as a starting platform to develop novel supportive therapy for patients
suffering from AD and to possibly prevent escalation of the disease in patients already having high-risk
factors for AD occurrence.
Phosphodiesterase 10 Inhibitors - Novel Perspectives for Psychiatric and Neurodegenerative Drug Discovery
Authors: Zagorska Agnieszka , Partyka Anna , Bucki Adam , Gawalskax Alicja , Czopek Anna , Pawlowski Maciej
Published: March 2018

Background:

The phosphodiesterase 10 (PDE10) family, identified in 1999, is
mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons,
nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually
rational subject for medicinal chemistry with potential use in the treatment of psychiatric
and neurodegenerative diseases.

Objective:

This review is based on peer-reviewed published articles, and summarizes the cellular
and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative
drug discovery. Here, we present the classification of PDE10-Is from a medicinal chemistry
point of view across a wide range of different, drug-like chemotypes starting from theophylline
and caffeine analogs, papaverine and dimethoxy catechol type PDE10-Is, TP-10,
MP-10, MP-10/papaverine/quinazoline series inhibitors, and ending with the newest inhibitors
obtained from fragment-based lead discovery (FBLD). The authors have collated recent research
on inhibition of PDE10A as a promising therapeutic strategy for psychiatric and neurodegenerative
diseases, based on its efficacy in animal models of schizophrenia, Parkinson’s,
Huntington’s, and Alzheimer’s diseases. This review also presents pharmacological data on
PDE10-Is as possible therapeutics for the treatment of cognitive deficits, obesity and depression.
Moreover, it summarizes the current strategies for PDE10-Is drug discovery based on
the results of clinical trials. The authors also present the latest studies on crystal structures of
PDE10 complexes with novel inhibitors.
Biological Activity of Trans-Membrane Anion Carriers
Authors: Tosolini Massimo , Pengo Paolo , Tecilla Paolo
Published: March 2018

Natural and synthetic anionophores promote the trans-membrane transport of
anions such as chloride and bicarbonate. This process may alter cellular homeostasis with
possible effects on internal ions concentration and pH levels triggering several and diverse
biological effects. In this article, an overview of the recent results on the study of aniontransporters,
mainly acting with a carrier-type mechanism, is given with emphasis on the
structure/activity relationship and on their biological activity as antibiotic and anticancer
agents and in the development of new drugs for treating conditions derived from dysregulation
of natural anion channels.
Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions
Authors: Benabdallah Mohammed , Talhi Oualid , Nouali Fatiha , Choukchou-Braham Nouredine , Bachari Khaldoun , Silva Artur M.S.
Published: March 2018

The present review deals with the progress in medicinal chemistry of spirocyclic
compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of
two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central
carbon confers to the molecules a tridimensional structurally oriented framework, which is
found in many medicinally relevant compounds, a well-known example is the antihypertensive
spironolactone. Various bioactive natural products possess the privileged spiro
linkage and different chemo-types thereof become synthetically accessible since the 20th century.
Actually, there has been a growing interest in the synthesis of heterocyclic hybrids gathered
via a spiro carbon. Most of these combinations are two moieties in one scaffold being
able to interfere with biological systems through sequential mechanisms. Spirocyclic hybrids
containing indole or oxindole units are compounds exhibiting higher interaction with biological
receptors by protein inhibition or enzymatic pathways and their recognition as promising
anticancer agents in targeted chemotherapy is foreseen. These specific, low-weight and noncomplex
spirocyclic hybrids are potent inhibitors of SIRT1, Mdm2–p53 and PLK4, showing
affinity for anaplastic lymphoma kinase (ALK) receptor. They are also known as excellent
DNA binders, acting on cellular division by arresting the cell cycle at different phases and inducing
apoptotic cell death. A structural diversity of spirocyclic hybrids has proved neuroprotective
effects, anti-HIV, antiviral and antibacterial activities. Hundred of papers are mentioned
in this review underlying chemical issues and pharmacological potencies of spiro compounds,
which render them impressive synthetic hits for innovative drug conception.
Development of the Biomaterials Technology for the Infection Resistance
Authors: Xu Tengzhou , Chen Zhou , Chen Zhaofeng , Fan Yuxin , Mao Haifeng
Published: March 2018

Infections caused by microbial proliferation are one of the common issues and serious threats to the
medical care, and they usually result in disease spread. Therefore, it is a significant issue for developing the antiinfective
biomaterials to control this problem, according to the specific clinical application. Meanwhile, all their
properties, the best anti-infective performance, the safe biocompatibility and the appropriate tissue interactions
must be conformed to each other. At present, technologies are developing novel biomaterials and surfaces endowed
with anti-infective properties, relying either on bactericidal or anti-biofilm activities. This review focuses
on thoroughly summarizing numerous kinds of antibacterial biomaterials, including the antibacterial matrix biomaterials,
antibacterial coatings and films, nanostructured materials and antibacterial fibers. Among these strategies,
the utilization of bio-glass base and graphene base antibacterial matrix, and their effects on the antibiosis
mechanism were emphatically discussed. Simultaneously, the effects and mechanisms of nano-coated metallic
ions are also mentioned. Overall, there is a wealth of technical solutions to contrast the establishment of an implant
infection. The lack of well-structured prospective multicenter clinical trials hinders the achievement of
conclusive data on the efficacy and comparative performance of antibacterial biomaterials.
Parp Inhibitors for the Treatment of Ovarian Cancer
Authors: Cortesi Laura , Toss Angela , Cucinotto Iole
Published: March 2018

The standard of treatment for advanced ovarian cancer is represented by optimal surgical
debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum
agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive
treatment strategy, almost 75% of patients relapse or progress and are therefore candidates
for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An
interesting approach to improve outcomes of these patients has been developed in the last decade, in
BRCA-related ovarian cancer. Mutations in one of the BRCA genes result in impaired homologousrecombination
DNA repair, which causes genetic abnormalities that promote carcinogenesis. Interestingly,
this defect has been exploited by the introduction of poly (ADP-ribose) polymerase (PARP)
inhibitors to provide specific cancer cell cytotoxicity. Particularly, the inhibition of PARP in BRCAmutation
carriers leads to the persistence of DNA damage usually repaired by the homologousrecombination
system, resulting in cell cycle arrest and thus apoptosis. Despite the mechanism of action,
an activity of PARP inhibitors was also observed in “BRCAness” ovarian tumors, and in
BRCA-related tumors other than ovarian, suggesting that these agents may be active regardless of
BRCA mutation status or site of origin. This review aims to describe the principal evidence that led
to the development and the study of PARP inhibitors and to discuss their main implications in our
daily clinical practice.
Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Authors: Mamoori Afraa , Gopalan Vinod , Lam Alfred K-Y
Published: March 2018

Background: There is emerging data suggesting that the non-coding RNA (microRNA
193a or miR-193a) plays key roles in different types of cancers.

Objective: This review aims to investigate the functional significance of miR-193a in different cancers
according to the information of literature.

Method: All the literature concerning miR-193a in cancer in PubMed are analysed.

Results: Several studies proved the association of miR-193a expression patterns with cancer’s
stages, grades, response to the chemotherapy and even patient survival. Also, miR-193a can be used
to differentiate some types of cancer. In cancer, miR-193a can act as a tumour suppressor gene or as
an oncogene. Till now, several genetic factors (MAX, RXR α, XB130, P63, P73, AEG-1, HIFs,
EGFR, Drosha, DGCR8, Dicer) and epigenetic factors (DNA methylation and long non-coding
RNAs) were predicted to control miR-193a expression. They have fundamental effects on its biological
behaviour in different types of cancers.

Conclusion: miR-193a has significant roles in cancer and can be targeted in the future for cancer
therapy by better understanding of the factors that control its biological behaviour.
Metastatic Site Location Influences the Diagnostic Accuracy of ctDNA EGFR- Mutation Testing in NSCLC Patients: a Pooled Analysis
Authors: Passiglia Francesco , Rizzo Sergio , Rolfo Christian , Galvano Antonio , Bronte Enrico , Incorvaia Lorena , Listi Angela , Barraco Nadia , Castiglia Marta , Calo Valentina , Bazan Viviana , Russo Antonio
Published: March 2018

Background:

Recent studies evaluated the diagnostic accuracy of circulating tumor DNA
(ctDNA) analysis in the detection of epidermal growth factor receptor (EGFR) mutations from
plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue
genotyping. However it is less clear if the location of metastatic site may influence the ability to
identify EGFR mutations.

Objective:

This pooled analysis aims to evaluate the association between the metastatic site location
and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients.

Methods:

Data from all published studies, evaluating the sensitivity of plasma-based EGFRmutation
testing, stratified by metastatic site location (extrathoracic (M1b) vs intrathoracic (M1a))
were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology,
and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence
intervals (95% CIs) were calculated for the ctDNA analysis sensitivity, according to metastatic
site location.

Results:

A total of ten studies, with 1425 patients, were eligible. Pooled analysis showed that the
sensitivity of ctDNA-based EGFR-mutation testing is significantly higher in patients with M1b vs
M1a disease (OR: 5.09; 95% CIs: 2.93 – 8.84). A significant association was observed for both
EGFR-activating (OR: 4.30, 95% CI: 2.35-7.88) and resistant T790M mutations (OR: 11.89, 95%
CI: 1.45-97.22), regardless of the use of digital-PCR (OR: 5.85, 95% CI: 3.56-9.60) or non-digital
PCR technologies (OR: 2.96, 95% CI: 2.24-3.91).

Conclusions:

These data suggest that the location of metastatic sites significantly influences the diagnostic
accuracy of ctDNA analysis in detecting EGFR mutations in NSCLC patients.
Quality by Design: Concept to Applications
Authors: Swain Suryakanta , Parhi Rabinarayan , Jena Bikash Ranjan , Babu Sitty Manohar
Published: March 2018

Background:

Quality by Design (QbD) is associated with a modern, systematic, scientific
and novel approach which is concerned with pre-distinct objectives that not only focus on product,
process understanding but also lead to process control. It predominantly signifies the design and product
improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final
products quality characteristics. It is quite essential to identify the desired and required product performance
report, such as Target Product Profile, typical Quality Target Product Profile (QTPP) and
Critical Quality Attributes (CQA).

Methods:

This review highlighted the concepts of QbD design space, for critical material attributes
(CMAs) as well as the critical process parameters that can totally affect the CQAs within which the
process shall be unaffected thus, consistently manufacturing the required product. Risk assessment tools
and design of experiments are its prime components.

Results:

This paper outlines the basic knowledge of QbD, the key elements; steps as well as various
tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot
of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized.

Conclusion:

This article provides a complete data as well as the roadmap for universal implementation
and application of QbD for pharmaceutical products.
Sorafenib as a Salvage Therapy in FLT3-ITD Negative Relapse/ Refractory Acute Myeloid Leukemia
Authors: Yang Nan , Gu Zhenyang , Liu Zhanxiang , Huang Wenrong , Wang Shuhong , Wang Lili , Gao Chunji
Published: March 2018

Background:

Multi-kinase inhibitor sorafenib showed dramatic effects in acute myeloid leukemia
(AML) cells harboring fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation.
However, FLT3-ITD mutation only occurs in 25% of AML cases. The therapeutic effects of sorafenib in AML
patients without FLT3-ITD are still in need of further investigation.

Methods:

A young AML patient with central nervous system (CNS) relapse was treated with sorafenib
combined with chemotherapy. Another patient with refractory AML arising form chronic myelomonocytic
leukemia (CMML) was treated with sorafenib monotherapy. Spinal and cranial magnetic resonance imaging (MRI),
minimal residual disease (MRD) and peripheral blood cell count were monitored to evaluate disease status.

Results:

The patient with CNS relapse exhibited significant shrink of tumor volume. The other patient with
refractory AML achieved hematological improvements.

Conclusion:

These two cases suggested that sorafenib might be utilized as a potent salvage therapy for some
refractory/relapsed AML patients without the FLT3-ITD mutation.
99mTc-(tricine)-HYNIC-Lys-FROP Peptide for Breast Tumor Targeting
Authors: Ahmadpour Sajjad , Noaparast Zohreh , Abedi Seyed Mohammad , Hosseinimehr Seyed Jalal
Published: March 2018

Background:

Breast cancer is a malignant disease with high mortality rate among women in the
world. It is necessary to diagnose breast cancer at the early stage before it metastasizes in patients.

Objective:

The aim of this study is the evaluation of 99mTc-(tricine)-HYNIC-Lys-FROP for breast tumor
imaging.

Method:

Lys-FROP peptide was labeled with 99mTc using HYNIC as chelator and tricine as co-ligand. Specific
binding of this radiolabeled peptide on breast cancerous cell was assessed in different cell lines as well as in
tumor-bearing mice.

Results:

HYNIC-Lys-FROP peptide was labeled with 99mTc at radiochemical purity more than 99%. It was
observed high stability in normal saline and serum about 95%. The highest cellular uptake was observed in
MCF-7 breast tumor cells treated with 99mTc-(tricine)-HYNIC-Lys-FROP as compared to other cell lines (lung,
ovarian, T47D breast cancer cell lines). Biodistribution results in female MCF-7 tumor-bearing mice showed the
relatively high tumor uptake and tumor-muscle ratio as 3.82 ± 0.66 after 15 min post-injection of 99mTc-(tricine)-
HYNIC-Lys-FROP. Tumor uptake was reduced in mice that were co-injected with excess of unlabeled peptide
to be 0.91 ± 0.08.

Conclusion:

Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular
imaging of breast cancer.
New Quinoline Based Sulfonamide Derivatives: Cytotoxic and Apoptotic Activity Evaluation Against Pancreatic Cancer Cells
Authors: Yurttaş Leyla , Çiftçi Gülşen A.
Published: March 2018

Background:

Quinoline is a privileged scaffold especially known with antimalarial and antibacterial
drugs before, presently followed anticancer efficiency with a new group of protein kinase inhibitors.

Objective:

In this work, combining quinoline ring, hydrazone and sulphonamide groups, we have synthesized
N'-arylidene-2-[4-(quinolin-8-ylsulfonyl)piperazin-1-yl]acetohydrazide derivatives (3a-o) and evaluated their in
vitro anticancer activity against cancerous cell lines PANC-1, CAPAN-1, and healthy cell line hTERT-HPNE.

Method:

Fifteen compounds were synthesized a simple, well-known three-step synthetic procedure starting
from 8-quinolinesulfonylchloride. Cytotoxicity studies were performed according to the conventional MTT
method. As a second stage, flow cytometric analysis was done to the nine most cytotoxic compounds for determining
the mechanism of action which could be apoptosis and/or necrosis.

Results/Conclusion: According to anticancer activity evaluation, compound 3b bearing 4-methyl phenyl moiety
exhibited significant cytotoxicity which has an IC50 value nearly four-fold lower than cisplatin displayed,
whereas compound 3f bearing 4-trifluoromethyl phenyl moiety showed two-fold potency of the standard drug
against PANC-1 cell line. Compounds 3h, 3k and 3n against CAPAN-1 also showed significant cytotoxicity,
selectively. The most active compounds 3b, 3c, 3d, 3f, 3g, 3h, 3k and 3n against PANC-1 and compounds 3f,
3g, 3h, 3k and 3n against CAPAN-1 were selected to be studied in flow cytometry. Compound 3b induced
apoptosis of PANC-1 cells with a percentage of 16.0%, whereas compound 3h induced apoptosis of CAPAN-1
cells with a value of 20.6%.
Spatial Variation of Metals in the Batang Arau River, West Sumatera, Indonesia
Authors: Indah Shinta , Helard Denny , Herfi Marjani Amajida , Hamid Hukama
Published: March 2018

This paper aims to assess metallic pollution in the Batang Arau River, an important source of freshwater supply for local communities in West Sumatera, Indonesia, by applying multivariate statistical techniques. Sampling was conducted at eight stations along the river from March to May 2014. The results indicate that all the metals studied have similar spatial distribution patterns, with an increasing trend in concentration from upstream to downstream. Total concentration of six metals studied upstream, as background concentration, was 1.050 mg/L, and increased to 2.249 mg/L downstream. Spatial distribution of metals did not show significant variability (p < 0.05) for Cd, Cr, Fe, and Pb, but Co and Mn did. The results of principal component analysis/factor analysis (PCA/FA) and correlation analysis suggest that Cd, Co, and Fe are originated from natural and anthropogenic sources; Cr and Pb are derived from natural sources; and Mn is controlled by anthropogenic sources.
Thermal Degradation of Long Chain Fatty Acids
Authors: Charuwat Peerawat , Boardman Gregory , Bott Charles , Novak John T.
Published: March 2018

The thermal hydrolysis of saturated (C16:0 and C18:0) and unsaturated fatty acids (C16:1, C18:1, and C18:2) was investigated at 90 °C to 160 °C for 30 min and 8 h durations. Hydrolysis efficiencies were calculated based on mass yield (i.e., mg/g parent compound), which accounted for all C2–C24 by‐products. Very little degradation (less than 1%) of long chain fatty acids (LCFAs) was observed from 30 min thermal hydrolysis. At 140 and 160 °C for 8 h, saturated fatty acids degraded uniformly to C2 to C14. Saturated fatty acids tended to convert to alkanes (1.5–2.0% of total fatty acids) instead of fatty acids (8 h). Thermal hydrolysis did not significantly affect unsaturated LCFA degradation at any duration. The unsaturated by‐products seen were the result of cleavage at the allylic or vinylic positions. Thermal hydrolysis of LCFAs with digested sludge was investigated. The amount of VFAs and LCFAs in primary and secondary sludge was increased at 140 and 160 °C as a result of lipid degradation in the sludge mixture. Thermal hydrolysis of fatty acids with different catalysts was also investigated. Whereas saturated LCFAs were stable under all catalytic conditions, unsaturated LCFAs were nearly completely degraded when hydrolyzed with hydrogen peroxide and activated carbon or copper sulfate.
A New Photocatalyst Bismuth Oxo Citrate: Synthesis, Characterization, and Photocatalytic Performance
Authors: Najdanović Slobodan M. , Petrović Milica M. , Slipper Ian J. , Kostić Miloš M. , Prekajski Marija D. , Mitrović Jelena Z. , Bojić Aleksandar Lj.
Published: March 2018

A new photocatalyst bismuth oxo citrate was synthesized by facile precipitation process with calcination at 200 °C. The photocatalyst was characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), Fourier‐transform infrared (FTIR) spectroscopy, N2sorptometry, and elemental analysis. Morphologically, it is composed of polyhedral particles with different, irregular shapes and sizes. The specific surface area (SSA) of the photocatalyst was 8.92 m2g–1. It showed very good photocatalytic performance and reusability. Total decolorization of Reactive Blue 19 (RB19) was achieved in less than 10 minutes, which is much faster in comparison with TiO2P25. Also, bismuth oxo citrate showed higher photocatalytic activity than other photocatalysts based on bismuth compounds reported by other authors. Optimal photocatalysis parameters were pH 2 and photocatalyst dose of 250 mg dm–3. The decolorization rate was found to decrease as initial dye concentration increased. The photocatalytic data best fitted to L–H kinetic model with pseudo‐first order reaction rate. Chrastil diffusion model showed that diffusion has not influence on the process.
Using Twitter to better understand online patient experience sentiments in the US (Preprint)
Authors: Sewalk Kara , Tuli Gaurav , Hswen Yulin , Brownstein John S , Hawkins Jared B
Published: March 2018

BACKGROUND

Traditional large-scale assessments of patient care in the US have difficulty in representing all aspects of health, beyond hospital care. There are documented differences in access to healthcare across the US. It is important to understand disparities in healthcare to better inform policy makers and healthcare administrations to improve quality of care provided. Previous research indicates online data is available from Twitter about patient experiences and opinions of their healthcare. Understanding patient views through sentiment analyses of Twitter data can be used to supplement traditional feedback surveys.

OBJECTIVE

We aim to provide a characterization of patient experience sentiments across the US on Twitter over a four year period.

METHODS

We developed a set of software components to auto-label and examine the patient experience Twitter dataset. The set includes: (I) a classifier to determine patient experience tweets, (II) a geolocation inference engine for social data, (III) a modified version of a sentiment classifier from the literature, and (IV) another engine to determine if the tweet is from a metro or non-metro area.

RESULTS

Of the 27.3 million tweets collected between February 2013 and February 2017 using a set of patient experience related keywords, the classifier was able to identify 2,779,555 tweets that were labeled as patient experience. After running the patient experience tweets through the geolocation classifier, we identified 876,384 tweets by approximate location to use for spatial analyses. At the national level, we observed 27.7% of positive, 36.3% neutral, 36% of negative Patient Experience tweets. Overall, the average sentiment polarity shifted towards less negative every year across all the regions in the country. The patient experience tweet rate also decreased across all the states over the four year study period. We also observed the sentiment of tweets to have a lower negative fraction during daytime hours, whereas the sentiment of tweets posted between 8pm and 10am tend to have a higher negative fraction. Additionally, tweet sentiment varied by region and by metro vs. non-metro analyses.

CONCLUSIONS

This study presents methodologies for a deeper understanding of online discussion related to patient experience across space and time, and demonstrates how Twitter can provide a unique and unsolicited perspective from users, which may not be captured from traditional survey methods for understanding patient views.
Public Opinions Toward Diseases: Infodemiological Study on News Media Data (Preprint)
Authors: Huang Ming , ElTayeby Omar , Zolnoori Maryam , Yao Lixia
Published: March 2018

BACKGROUND

Society always has limited resources to expend on health care, or anything else. What are the unmet medical needs? How do we allocate limited resources to maximize the health and welfare of the people? These challenging questions might be re-examined systematically within an infodemiological frame on a much larger scale, leveraging the latest advancement in information technology and data science.

OBJECTIVE

We expanded our previous work by investigating news media data to reveal the coverage of different diseases and medical conditions, together with their sentiments and topics in news articles over three decades. We were motivated to do so since news media plays a significant role in politics and affects the public policy making.

METHODS

We analyzed over 3.5 million archive news articles from Reuters media during the periods of 1996/1997, 2008 and 2016, using summary statistics, sentiment analysis, and topic modeling. Summary statistics illustrated the coverage of various diseases and medical conditions during the last 3 decades. Sentiment analysis and topic modeling helped us automatically detect the sentiments of news articles (ie, positive versus negative) and topics (ie, a series of keywords) associated with each disease over time.

RESULTS

The percentages of news articles mentioning diseases and medical conditions were 0.44%, 0.57% and 0.81% in the three time periods, suggesting that news media or the public has gradually increased its interests in medicine since 1996. Certain diseases such as other malignant neoplasm (34%), other infectious diseases (20%), and influenza (11%) represented the most covered diseases. Two hundred and twenty-six diseases and medical conditions (97.8%) were found to have neutral or negative sentiments in the news articles. Using topic modeling, we identified meaningful topics on these diseases and medical conditions. For instance, the smoking theme appeared in the news articles on other malignant neoplasm only during 1996/1997. The topic phrases HIV and Zika virus were linked to other infectious diseases during 1996/1997 and 2016, respectively.

CONCLUSIONS

The multi-dimensional analysis of news media data allows the discovery of focus, sentiments and topics of news media in terms of diseases and medical conditions. These infodemiological discoveries could shed light on unmet medical needs and research priorities for future and provide guidance for the decision making in public policy.
Early Psychosis Service User Views on Digital Technology: Qualitative Analysis (Preprint)
Authors: Bucci Sandra , Morris Rohan , Berry Katherine , Berry Natalie , Haddock Gillian , Barrowclough Christine , Lewis Shôn , Edge Dawn
Published: March 2018

BACKGROUND

Digital technology has the potential to improve outcomes for people with psychosis. However, to date, research has largely ignored service user views on digital health interventions (DHIs).

OBJECTIVE

The objective of our study was to explore early psychosis service users’ subjective views on DHIs.

METHODS

Framework analysis was undertaken with data obtained from 21 semistructured interviews with people registered with early intervention for psychosis services. Robust measures were used to develop a stable framework, including member checking, triangulation, independent verification of themes, and consensus meetings.

RESULTS

The following 4 themes were established a priori: acceptability of technology in psychosis and mental health; technology increasing access to and augmenting mental health support; barriers to adopting DHIs; and concerns about management of data protection, privacy, risk, and security of information. The following 2 themes were generated a posteriori: blending DHIs with face-to-face treatment and empowerment, control, and choice. DHIs were also viewed as potentially destigmatizing, overcoming barriers faced in traditional service settings, facilitating communication, and empowering service users to take active control of their health care.

CONCLUSIONS

In the first study of its kind, early psychosis service users’ were largely positive about the potential use of DHIs supporting and managing mental health. Overall, service users felt that DHIs were a progressive, modern, and relevant platform for health care delivery. Concerns were expressed around privacy and data security and practical barriers inherent within DHIs, all of which require further attention. Future research should explore whether findings transfer to other service user groups, other technology delivery formats, and across a range of treatment modalities.
#Healthy Selfies: Exploration of Health Topics on Instagram (Preprint)
Authors: Muralidhara Sachin , Paul Michael J.
Published: March 2018

BACKGROUND

Social media provides a complementary source of information for public health surveillance. The dominate data source for this type of monitoring is the microblogging platform Twitter, which is convenient due to the free availability of public data. Less is known about the utility of other social media platforms, despite their popularity.

OBJECTIVE

This work aims to characterize the health topics that are prominently discussed in the image-sharing platform Instagram, as a step toward understanding how this data might be used for public health research.

METHODS

The study uses a topic modeling approach to discover topics in a dataset of 96,426 Instagram posts containing hashtags related to health. We use a polylingual topic model, initially developed for datasets in different natural languages, to model different modalities of data: hashtags, caption words, and image tags automatically extracted using a computer vision tool.

RESULTS

We identified 47 health-related topics in the data (kappa=.77), covering ten broad categories: acute illness, alternative medicine, chronic illness and pain, diet, exercise, health care & medicine, mental health, musculoskeletal health and dermatology, sleep, and substance use. The most prevalent topics were related to diet (8,293/96,426; 8.6% of posts) and exercise (7,328/96,426; 7.6% of posts).

CONCLUSIONS

A large and diverse set of health topics are discussed in Instagram. The extracted image tags were generally too coarse and noisy to be used for identifying posts but were in some cases accurate for identifying images relevant to studying diet and substance use. Instagram shows potential as a source of public health information, though limitations in data collection and metadata availability may limit its use in comparison to platforms like Twitter.
Monitoring Interest in Herpes Zoster Vaccination: Analysis of Google Search Data (Preprint)
Authors: Berlinberg Elyse J , Deiner Michael S , Porco Travis C , Acharya Nisha R
Published: March 2018

BACKGROUND

A new recombinant subunit vaccine for herpes zoster (HZ or shingles) was approved by the United States Food and Drug Administration on October 20, 2017 and is expected to replace the previous live attenuated vaccine. There have been low coverage rates with the live attenuated vaccine (Zostavax), ranging from 12-32% of eligible patients receiving the HZ vaccine.

OBJECTIVE

This study aimed to provide insight into trends and potential reasons for interest in HZ vaccination.

METHODS

Internet search data were queried from the Google Health application programming interface from 2004-2017. Seasonality of normalized search volume was analyzed using wavelets and Fisher’s g test.

RESULTS

The search terms “shingles vaccine,” “zoster vaccine,” and “zostavax” all exhibited significant periodicity in the fall months (P<.001), with sharp increases after recommendations for vaccination by public health-related organizations. Although the terms “shingles blisters,” “shingles itch,” “shingles rash,” “skin rash,” and “shingles medicine” exhibited statistically significant periodicities with a seasonal peak in the summer (P<.001), the terms “shingles contagious,” “shingles pain,” “shingles treatment,” and “shingles symptoms” did not reveal an annual trend.

CONCLUSIONS

There may be increased interest in HZ vaccination during the fall and after public health organization recommendations are broadcast. This finding points to the possibility that increased awareness of the vaccine through public health announcements could be evaluated as a potential intervention for increasing vaccine coverage.
Computer-Aided Telephone Support for Primary Care Patients with Common Mental Health Conditions: Randomized Controlled Trial (Preprint)
Authors: Zaheer Salaha , Garofalo Vanessa , Rodie David , Perivolaris Athina , Chum Jenny , Crawford Allison , Geist Rose , Levinson Andrea , Mitchell Brian , Oslin David , Sunderji Nadiya , Mulsant Benoit H. ,   PARTNERs Study Group
Published: March 2018

BACKGROUND

Depression, anxiety, and at-risk drinking are highly prevalent in primary care settings. Many jurisdictions experience geographical barriers to accessing mental health services, necessitating the development and validation of alternative models of care delivery. Existing evidence supports the acceptability and effectiveness of providing mental health care by telephone.

OBJECTIVE

This analysis assesses patient’s acceptability of computer-aided telephone support delivered by lay providers to primary care patients with depression, anxiety, or at-risk drinking.

METHODS

The Primary care Assessment and Research of a Telephone intervention for Neuropsychiatric conditions with Education and Resources study is a randomized controlled trial comparing a computer-aided telephone-based intervention to usual care enhanced by periodic assessments in adult primary care patients referred for the treatment of depression, anxiety, or at-risk drinking; no part of the study involves in-person contact. For this analysis, the following data were obtained: reasons provided for declining consent; reasons provided for withdrawing from the study; study retention rate; and a thematic analysis of a satisfaction survey upon study completion.

RESULTS

During the consent process, 17.1% (114/667) patients referred to the study declined to participate and 57.0% of them (65/114) attributed their refusal to research-related factors (ie, randomization and time commitment); a further 16.7% (19/114) declined owing to the telephone delivery of the intervention. Among the 377 participants who were randomized to the 1-year intervention, the overall retention rate was 82.8% (312/377). Almost no participants who withdrew from the study identified the telephone components of the study as their reason for withdrawal. Analysis of a qualitative satisfaction survey revealed that 97% (38/39) of comments related to the telephone components were positive with key reported positive attributes being accessibility, convenience, and privacy.

CONCLUSIONS

Our results suggest that a computer-aided telephone support is highly acceptable to primary care patients with depression, anxiety, or at-risk drinking. In particular, these patients appreciate its accessibility, flexibility, and privacy.

CLINICALTRIAL

ClinicalTrials.gov NCT02345122; https://clinicaltrials.gov/ct2/show/NCT02345122 (Archived by WebCite at http://www.webcitation.org/73R9Q2cle)