bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geocoding for public health research: Empirical comparison of two geocoding services applied to Canadian cities
Authors: Shah Tayyab Ikram , Bell Scott , Wilson Kathi 
Published: May 2014

AbstractThe process of geocoding, particularly the street address matching process, is a commonly used technique to obtain locational information for public health research. In health care accessibility research, geocoded locations of health care providers are an essential element for measuring potential access to health care. Our objective is to compare the geocoding match rates and positional variation of two geocoding procedures by using street network and postal code datasets to geocode primary health care services in 14 cities. The first procedure uses a manually built geocoding service using DMTI Spatial (DMTI) reference datasets while the second employs an online geocoding service provided as a built‐in tool in ArcGIS, with ESRI Tele Atlas reference datasets. Results for Tele Atlas postal code and DMTI multiple enhanced postal codes (MEP) reference datasets produce much higher match rates (99.4%; 98.0% respectively) than street reference datsasets; while results of Tele Atlas street dataset produce better match rates (96.5%) than the DMTI street dataset (90.0%). Geocoding methods using Tele Atlas and DMTI Street datasets produce more accurate locations than postal code and MEP reference datasets. Empirical comparison of the geocoding results based on manually built and online geocoding services highlight the need for integrated geocoding procedures for increasing match rates with reduced positional uncertainty.
Hapten Optimization for Cocaine Vaccine with Improved Cocaine Recognition
Authors: Ramakrishnan Muthu , Kinsey Berma M. , Singh Rana A. , Kosten Thomas R. , Orson Frank M. 
Published: May 2014

In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anticocaine antibodies, none of the hapten was successfully designed, which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl norcocaine (HNC), bromoacetamido butyl norcocaine (BNC), and succinyl butyl norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anticocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titre anticocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed, and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate, vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Although we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore, it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50) value for SBNC antibodies (2.8 μm) was significantly better than the SNC antibodies (9.4 μm) when respective hapten–BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4 °C and 2–3 days in pH 10 buffer at 37 °C.
Arylazopyrazole AAP1742 Inhibits CDKs and Induces Apoptosis in Multiple Myeloma Cells via Mcl‐1 Downregulation
Authors: Jorda Radek , Navrátilová Jana , Hušková Zlata , Schütznerová Eva , Cankař Petr , Strnad Miroslav , Kryštof Vladimír 
Published: May 2014

Inhibitors of cyclin‐dependent kinases 9 have been developed as potential anticancer drugs for the treatment of multiple myeloma. We have previously prepared a library of arylazo‐3,5‐diaminopyrazole inhibitors of CDKs. Here, we describe a novel member, AAP1742 (CDK9 inhibition with IC50 = 0.28 μm), that reduces the viability of multiple myeloma cell lines in low micromolar concentrations. Consistent with inhibition of CDK9, AAP1742 decreases the phosphorylation of RNA polymerase II and inhibits mRNA synthesis of anti‐apoptotic proteins Mcl‐1, Bcl‐2, and XIAP, followed by apoptosis in the RPMI‐8226 cell line in a dose‐ and a time‐dependent manner. These results are consistent with the biochemical profile of AAP1742 and further suggest cellular inhibition of CDK9 as a possible target for anticancer drugs.
Highly Potential Antiplasmodial Restricted Peptides
Authors: Marcelo Der Torossian Torres , Silva Adriana F. , Alves Flávio L. , Capurro Margareth L. , Miranda Antonio , Vani Xavier Oliveira 
Published: May 2014

Malaria is an infectious disease responsible for approximately one million deaths annually. The antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and P. falciparum have recently been reported. To evaluate antiplasmodial activity, we synthesized five angiotensin II‐restricted analogs containing disulfide bridges. To accomplish this, peptides containing two inserted amino acid residues (cysteine) were synthesized by the Fmoc solid‐phase method, purified by liquid chromatography, and characterized by mass spectrometry. Conformational studies were performed by circular dichroism. The results indicated that two of the analogs had higher antiplasmodium activity (92% and 98% activity) than angiotensin II (88% activity), measured by fluorescence microscopy. Results showed that the insertion position must be selected, to preserve the hydrophobic interactions between the non‐polar residues, as this affects antiplasmodial activity. The circular dichroism studies suggested that the active analogs as well as the native angiotensin II adopt a β‐turn conformation in different solutions. This approach provided insight for understanding the effects of restricting the ring size and position on the bioactivity of angiotensin II and provides a new direction for the design of potential chemotherapeutic agents.
Exposure of children with developmental delay to social determinants of poor health: cross‐sectional case record review study
Authors: Emerson E. , Brigham P. 
Published: May 2014

AbstractBackgroundResearch on child development in general has highlighted the importance that the family environment plays in mediating the pathway between exposure to low socio‐economic position (SEP) and child well‐being. While child developmental models in intellectual disability have highlighted the interplay between social context, family environment and child development, little empirical work has attempted to formally evaluate the evidence in support of specific mediating pathways between low SEP and child outcomes.MethodsSecondary analysis of cross‐sectional confidentialized needs analysis data collected in three Primary Care Trusts in England covering a total population of 1.25 million people. Case record reviews were undertaken for 46 023 households, 2236 (4.9%) of which contained a child in the target age range with developmental delay.ResultsChildren with developmental delay, when compared with their non‐disabled peers, were at significantly increased risk of poorer health outcomes and of being exposed to a wide range of social determinants of poor health. Controlling for between‐group differences in exposure to social determinants of poor health reduced the risk of developmental delay being associated with poorer health outcomes by 45% for behaviour problems and 89% for risk of significant harm. For children with developmental delay, parenting difficulties appears to play a particularly significant role in partially mediating the effects of low SEP.ConclusionsThe findings of the present study point to the potential effectiveness of family‐focused early intervention to prevent the emergence and escalation of behavioural difficulties and health problems in children with developmental delay.
Neonatal blood TSH concentration in Wales (UK): an indicator of iodine sufficiency
Authors: Evans Carol , Barry Nix Arthur , Hillier Sharon , Moat Stuart J. 
Published: May 2014

SummaryObjectivePopulation iodine status can be assessed by urinary iodine concentrations, prevalence of goitre, frequency of newborn thyroid‐stimulating hormone (TSH) >5 mU/l and blood thyroglobulin concentrations. The UK population has historically been considered to be iodine sufficient; however, a recent survey of UK schoolgirls has demonstrated median urinary iodine concentrations consistent with mild iodine deficiency. The aim of our study was to assess the prevalence of TSH >5 mU/l in the newborn blood spot screening samples from the eligible population in Wales between 2011 and 2013 to assess iodine sufficiency.MeasurementsBlood spot TSH data for 104 992 infants during this time period were evaluated.ResultsThe prevalence of TSH >5 mU/l in samples collected on days 4 and 5 of life were 1·5% and 0·9%, respectively. No increasing trend in blood spot TSH concentration was identified over the 3 years.ConclusionsThe distribution of blood spot TSH data from neonates in Wales has revealed no evidence to support the hypothesis that the population is iodine deficient. However, given that mild iodine deficiency has been reported in a cohort that will be childbearing in the next decade, we recommend that the distribution of neonatal blood spot TSH concentrations is monitored by the UK newborn screening programmes to identify any emerging trends in iodine status. Further studies to correlate maternal urinary iodine and newborn blood spot TSH are required to clarify the TSH cut‐off points associated with mild iodine deficiency relevant to the time of blood spot sampling in the UK.
Usefulness of dynamic MRI enhancement measures for the diagnosis of ACTH‐producing pituitary adenomas
Authors: Guo Qinghua , Young William F. , Erickson Dana , Erickson Bradley 
Published: May 2014

SummaryPurposeThe distinction between corticotropin (ACTH)‐producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH‐producing pituitary adenomas.Materials and methodsFifty‐five patients with pathology confirmed ACTH‐producing and 44 with nonfunctioning pituitary adenomas were analysed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time–intensity curves were then constructed, and quantitative analysis included: enhancement time, enhancement peak and prepeak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters.ResultsQuantitative analysis showed that tumour PPS in ACTH‐producing adenomas was markedly lower than that in nonfunctioning adenomas (P = 0·0042) and that the PPS of the adjacent pituitary gland was not different (P = 0·2441). The PPS was >3·0 in 59·1% of nonfunctioning adenomas and ≤3·0 in 69·1% of ACTH‐producing adenomas (P = 0·0049). Logistic analysis revealed lower tumour PPS levels (P = 0·0123, OR 1·24, 95% CI: 1·05–1·52) were associated with ACTH‐producing adenomas. The optimal PPS cut‐off determined by ROC analysis was 2·89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak.ConclusionEnhancement parameters in DMRI can help distinguishing ACTH producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH‐producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.
Loss of ERβ expression in papillary thyroid carcinoma is associated with recurrence in young female
Authors: Ahn Hwa Young , Kim Min Suk , Kim Min Joo , Cho Soo Youn , Kim Young A , Lee Guk Haeng , Lee Byeong‐Cheol , Park Young Joo , Yi Ka Hee 
Published: May 2014

SummaryObjectivesWe investigated the expression of oestrogen receptors (ERs) in papillary thyroid cancers (PTCs) and evaluated their prognostic role.MethodsWe enrolled 81 female patients who underwent thyroid surgery and had a confirmed diagnosis of PTC between 01 January 1995 and 31 December 1996. Data on clinicopathologic parameters were obtained from patients' medical records. Tissue paraffin blocks of these 81 patients were collected for immunohistochemistry for ERα and ERβ.ResultsERα expression was observed in only eight patients (9·9%). In contrast, ERβ expression was positive in 36 (44·4%) patients. Total thyroidectomy (84·4% vs 61·1%, P = 0·017) and cervical lymph node metastasis (62·2% vs 22·2%, P = 0·000) were more frequent in the ERβ‐negative group than in the ERβ‐positive group. Among younger female patients (<45 years), the ERβ‐negative group showed a tendency towards more frequent recurrent or persistent disease than the ERβ‐positive group (42·3% vs 13·6%, P = 0·029). In contrast, the ERα‐positive group showed more recurrent or persistent disease than the ERα‐negative group in older female patients (100% vs 24·1%, P = 0·024). In multivariate analysis, ERβ negativity, extrathyroidal invasion and radioactive iodine treatment were risk factors for recurrence in young female patients.ConclusionLoss of ERβ expression was associated with recurrence in young female PTC patients. This finding suggests that oestrogen might play a protective role in the progression of PTC via ERβ, especially in young female patients.
Factors associated with prospective leptin concentrations throughout pregnancy in pregestational normal weight, overweight and obese women
Authors: Franco‐Sena Ana Beatriz , de Oliveira Livia Costa , de Jesus Pereira Pinto Thatiana , Farias Dayana Rodrigues , Vaz Juliana dos Santos , Kac Gilberto 
Published: May 2014

SummaryBackgroundLeptin concentrations increase throughout pregnancy but little is known about factors that influence this physiological change and whether they differ according to pregestational body mass index (BMI).ObjectiveTo assess whether longitudinal trends of leptin in pregnancy are influenced by biochemical, anthropometric and lifestyle factors in women with normal weight (NW), overweight (OW) or obese (OB) pregestational BMI.Design and methodsProspective cohort of 232 pregnant women followed at 5–13th, 20–26th and 30–36th gestational weeks. The effect of selected variables on longitudinal behaviour of plasma leptin concentrations, stratifying for NW (18·5–24·9 kg/m2), OW (25–29·9 kg/m2) and OB (≥30·0 kg/m2) pregestational BMI was assessed through longitudinal linear mixed‐effects models.ResultsThe multiple regression model for women with NW revealed associations of maternal body weight (β = 0·714, CI = 0·491 to 0·937), serum HDL‐cholesterol (β = 0·239, CI =0·089 to 0·388) and C‐reactive protein (CRP) (β = −0·138, CI = −0·272 to −0·004) with plasma leptin concentrations. Maternal body weight (β = −0·871, CI = 0·475 to 1·267) and serum HDL‐cholesterol concentrations (β = 0·315, CI = −0·022 to 0·651) were also associated with leptin in OW women. In OB women, serum HDL‐cholesterol (β = 0·722, CI = 0·219 to 1·226), maternal body weight (β = 0·666, CI = 0·187 to 1·145), triglycerides concentrations (β = −0·130, CI = −0·241 to −0·020) and dietary carbohydrate (β = 0·075, CI = 0·023 to 0·126) were significantly associated with plasma leptin.ConclusionMaternal body weight and serum concentrations of HDL‐cholesterol were associated with leptin changes independent of pregestational BMI. Serum CRP concentrations were associated with leptin only in NW women and serum triglycerides concentrations and dietary carbohydrate only in OB. These results indicate that factors that influence leptin concentrations differ according to pregestational BMI.
Pulmonary hypoplasia presenting with recurrent wheezing in an infant
Authors: Çeliksoy Mehmet Halil , Tander Burak , Aşılıoğlu Nazik , Barış Yakup Sancar , Yıldıran Alişan 
Published: May 2014

AbstractPulmonary hypoplasia is characterized by decrease in the number and size of pulmonary airways, alveoli and vessels. In autopsy, pulmonary hypoplasia is a major cause of death in neonates and infants. The disease is usually diagnosed in childhood period. Although it mimics lung parenchymal disease and other vascular abnormalities radiologically, it is easily recognized with computed tomography angiography and magnetic resonance angiography examinations. In 50% of patients, concomitant cardiovascular, neuromuscular, gastrointestinal tract, and urogenital anomalies are also available. There are two types of pulmonary hypoplasia: primary and secondary. Primary unilateral pulmonary hypoplasia may be asymptomatic and the tendency for bronchopulmonary infections is often increased in children. In this case report, a 22‐month‐old male patient characterized by recurrent infections and recurrent wheezes in infantile period, whose episodes of wheezing regressed after the pulmonectomy, was presented.
Relationship between angiotensin‐converting enzyme gene polymorphism and respiratory distress syndrome in premature neonates
Authors: Hussein Nouran Fahmy , Abdel Ghany Eman Abdel Ghany , Abu Elhamed Walaa Alsharany , Samy Rania Mohamed 
Published: May 2014

AbstractObjectiveThe aim of this study was to investigate the possible relationship between angiotensin‐converting enzyme (ACE) gene polymorphism (D/D and I/D genotypes) and respiratory distress syndrome (RDS) in preterm neonates.Study DesignOur study included 120 preterm neonates (<37 weeks of gestation) with RDS (the patient group) and 120 preterm neonates without RDS (the control group). Blood samples were obtained from patients and control groups, and ACE gene polymorphism was analysed using the polymerase chain reaction method.ResultsD/D genotype was highly significant in the patient group compared with the control group (48.3% of RDS group vs 20% of the control group, P < 0.001). Meanwhile, I/D and I/I genotypes were significantly higher in the control group (75% and 5% of the control group vs 50% and 1.7% of the patient group, P < 0.001). D/D genotype was highly significant in neonates with bronchopulmonary dysplasia (BPD) compared with I/D genotype (P = 0.001).ConclusionOur results may suggest that D/D genotype is associated with increased risk of RDS and BPD development in preterm neonates.
The policy of placing older donors into older recipients: is it worth the risk?
Authors: Tehrani Yonah Solaiman , Yu Zhe , Luu Minh , Liou Frank , Rafiei Matthew , Hamilton Michele , Kobashigawa Jon A. 
Published: May 2014

AbstractBackgroundTo expand the donor pool, older donors (≥50 yr) are frequently used in older recipients (≥60 yr). Older recipients and those receiving older donor hearts have independently displayed decreased post‐transplant survival. However, outcomes in older patients receiving older donor hearts are contentious.MethodsEight hundred and seventy‐nine heart transplant patients between 2000 and 2010 were analyzed, excluding patients with donor coronary artery disease. From 380 patients ≥60 yr, 327 patients with donors <50 yr old were compared with 53 patients with donors ≥50 yr old for: five‐yr actuarial survival, freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), non‐fatal major adverse cardiac events (NF‐MACE: MI, CHF, stroke, need for pacemaker/ICD), one‐yr freedom from any treated rejection.ResultsThe older vs. younger donor group demonstrated significantly lower five‐yr survival (57% vs. 85%, p < 0.001) and freedom from CAV (83% vs. 92%, p = 0.03). No difference was observed in five‐yr freedom from NF‐MACE and one‐yr freedom from any treated rejection. Multivariate analysis found donor age ≥50 to be an independent risk factor for death (HR 1.8, CI 1.1–2.9, p = 0.008) and CAV (HR 1.9, CI 1.2–2.9, p = 0.004).ConclusionsUse of older donors (≥50 yr) in older recipients (≥60 yr) results in lower five‐yr survival and freedom from CAV. Caution is required in these cases. Larger studies are warranted to confirm findings.
Pfizer‐sponsored satellite symposium at the European Haemophilia Consortium (EHC) Congress
Authors: O'Mahony Brian , Kent Alastair , Aymé Ségolène 
Published: May 2014

AbstractThe annual European Haemophilia Consortium (EHC) Conference 2013, held in Bucharest, Romania, 4–5 October, was attended by over 200 patient advocates, policy makers and healthcare professionals from across Europe. Pfizer sponsored a satellite symposium at the conference entitled: ‘Changing the policy landscape: haemophilia patient involvement in healthcare decision making’, drawing on expertise from a panel specialising in the field of rare disease. The symposium, chaired by Declan Noone (Irish Haemophilia Society) on behalf of Brian O'Mahony (Irish Haemophilia Society), examined the current policy and economic landscape in Europe and how pressures on healthcare budgets are impacting haemophilia care. The symposium also discussed the importance of representing the ‘patient voice’ in key policy decisions through identification of opportunities for patient advocacy group engagement. Alastair Kent (Genetic Alliance UK) opened the session by highlighting that the downturn in the global economy has refocused decision‐making in healthcare, moving cost‐effectiveness of healthcare interventions higher up the agenda for decision‐makers and payers. In light of this, patient engagement is more important than ever, particularly in healthcare technology assessments (HTAs), to ensure that patient and family opinions are represented. Ségolène Aymé (Orphanet) built upon this in her session discussing the rare disease policy landscape and regional initiatives taking place in Europe, including the EUROPLAN process, for which the participation of the haemophilia community is critical. Finally, Declan Noone provided an example of how the EHC, through its survey of 35 countries, demonstrated not only the considerable differences in the quality of care available for people with haemophilia across Europe, but also how the data from the survey could be used as a powerful advocacy tool to initiate change in countries with lower gross domestic product (GDP) that face healthcare spending challenges. The meeting closed with a ‘call to action’ for patient advocacy groups, focusing on avenues by which patients can become involved in the decision‐making for policies that will ultimately affect access to, and quality of, haemophilia care in their country.