bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homozygous Familial Hypercholesterolemia in Spain
Authors: Sánchez-Hernández Rosa M. , Civeira Fernando , Stef Marianne , Perez-Calahorra Sofía , Almagro Fátima , Plana Nuria , Novoa Francisco J. , Sáenz-Aranzubía Pedro , Mosquera Daniel , Soler Cristina , Fuentes Francisco J. , Brito-Casillas Yeray , Real Jose T. , Blanco-Vaca Francisco , Ascaso Juan F. , Pocovi Miguel 
Published: October 2016

Background—

Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (
LDLR
), apolipoprotein B (
APOB
), proprotein convertase subtilisin/kexin type 9 (
PCSK9
), and LDL protein receptor adaptor 1 (
LDLRAP1
). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain.

Methods and Results—

Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH—of whom, 47 were true homozygous (1 for
APOB
, 5 for
LDLRAP1
, and 41 for
LDLR
), 45 compound heterozygous for
LDLR
, 3 double heterozygous for
LDLR
and
PSCK9
, and 2 double heterozygous for
LDLR
and
APOB
. No
PSCK9
homozygous cases were identified. Two variants in
LDLR
were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events.

Conclusions—
HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.
The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis
Authors: Aoki Yuta , Yamaguchi Sosei , Ando Shuntaro , Sasaki Natsuki , Bernick Peter J , Akiyama Tsuyoshi 
Published: October 2016

Background: Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment. Aims: The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT. Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen’s d) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model. Results: Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT. Conclusion: Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option.
Voluntary vs Compulsory Playing Contexts
Authors: Rodríguez-Aflecht Gabriela , Hannula-Sormunen Minna , McMullen Jake , Jaakkola Tomi , Lehtinen Erno 
Published: October 2016

Background. Serious games are often used in formal school contexts, in which students’ lack of control over the playing situation may have repercussions on any motivational gains. Aims and Method. The first aim was to investigate to what extent n = 579 fifth grade students in Mexico who received a mathematics serious game played it voluntarily. Then, we explored how students who played voluntarily ( n = 337) differed from those who did not by either gender or pre-test mathematical skills or motivation. The second aim was to find out whether two play contexts, the group of voluntary players and a second group consisting of students playing at school as a compulsory part of their regular mathematics lessons ( n = 482), differed in game experience, game performance, and cognitive and motivational outcomes. Results. Students from the volunteer group who played had higher pre-test mathematical skills and math interest than those who did not play. Students in this group did not otherwise differ. Compared to students from the volunteer group who played, students in the school group played for longer, completed more tasks, and enjoyed playing the game more. However, their advanced mathematical skills did not improve as much. Conclusion. Motivation did not improve regardless of play context, suggesting serious games should be implemented for their learning content rather than because they are assumed to be motivating.
Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure
Authors: Sargento Luis , Simões Andre Vicente , Longo Susana , Lousada Nuno , Reis Roberto Palma dos 
Published: October 2016

Background: Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). Aim: To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Population and Methods: Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. Results: The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score–matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Conclusion: Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.
Durability of the beneficial effect of MLC601 (NeuroAiD™) on functional recovery among stroke patients from the Philippines in the CHIMES and CHIMES-E studies
Authors: Navarro Jose C , Chen Christopher LH , Lee Chun F , Gan Herminigildo H , Lao Annabelle Y , Baroque Alejandro C , Hiyadan John Harold B , Chua Carlos L , San Jose Ma Cristina , Advincula Joel M , Venketasubramanian Narayanaswamy ,   for the CHIMES and CHIMES-E Study Investigators
Published: October 2016

Background and Aim A pre-specified country analysis of subjects from the Philippines in the CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) Study showed significantly improved functional and neurological outcomes on MLC601 at month (M) 3. We aimed to assess these effects on long-term functional recovery in the Filipino cohort. Methods The CHIMES-E (extension) Study evaluated subjects who completed three months of randomized placebo-controlled treatment in CHIMES up to two years. Blinding of treatment allocation was maintained and all subjects received standard stroke care and rehabilitation. Modified Rankin Score (mRS) and Barthel Index (BI) were assessed in-person at M3 and by telephone at M6, M12, M18, M24. Odds ratios (OR) with corresponding 95% confidence intervals (CI) for functional recovery using ordinal analysis of mRS and for achieving functional independence (mRS 0-1 or BI ≥ 95) at each time point were calculated, adjusting for age, sex, baseline National Institute of Health Stroke Scale (NIHSS), onset-to-treatment time (OTT) and pre-stroke mRS. Results The 378 subjects (MLC601 192, placebo 186) included in CHIMES-E from the Philippines (mean age 60.2 ± 11.1) had more women ( p < 0.001), worse baseline NIHSS ( p < 0.001) and longer onset to treatment time ( p = 0.002) compared to other countries. Baseline characteristics were similar between treatment groups. The treatment effect of MLC601 seen at M3 peaked at M6 with OR for mRS shift of 1.53 (95% CI 1.05–2.22), mRS dichotomy 0–1 of 1.77 (95% CI 1.10–2.83), and BI ≥ 95 of 1.87 (95% CI 1.16–3.02). The beneficial effect persisted up to M24. Conclusion The beneficial effect of MLC601 seen at M3 in the Filipino cohort is durable up to two years after stroke.
Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke
Authors: Luitse Merel JA , Velthuis Birgitta K , Kappelle L Jaap , van der Graaf Yolanda , Biessels Geert Jan ,   on behalf of the DUST Study Group
Published: October 2016

Background Acute hyperglycemia is associated with poor functional outcome after ischemic stroke, but the association between chronic antecedent hyperglycemia and outcome is unclear. Aim We assessed the association between chronic hyperglycemia, measured by hemoglobin A1c, and functional outcome in patients with acute ischemic stroke. Methods We included 812 patients with acute ischemic stroke (mean age 66 ± 14 years; 61.5% male). Patients were categorized per hemoglobin A1c level: no (<39 mmol/mol), moderate (39–42 mmol/mol), or severe chronic hyperglycemia (>42 mmol/mol). Poor functional outcome was defined as modified Rankin Scale score > 2 after 3 months. The relation between chronic hyperglycemia and functional outcome was assessed with a Poisson regression analysis and expressed as risk ratios with 95% confidence intervals with no chronic hyperglycemia as the reference. Results Moderate chronic hyperglycemia was present in 234 (28.8%) patients and severe chronic hyperglycemia in 183 (22.5%) patients. Acute hyperglycemia on admission was present in 338 (41.6%) patients. Severe chronic hyperglycemia was associated with poor outcome (risk ratios 1.40; 95% confidence interval 1.09–1.79). After adjustment for age, sex, stroke severity, vascular risk factors, and acute hyperglycemia on admission the risk ratios was 1.35 (95% confidence interval 1.04–1.76). Moderate chronic hyperglycemia was not associated with poor outcome (risk ratios 1.12; 95% confidence interval 0.87–1.44). Conclusion Severe chronic hyperglycemia is associated with poor functional outcome in patients with acute ischemic stroke. This association is independent of hyperglycemia in the acute stage of stroke and of an unfavorable vascular risk factor profile.
Radiolucent Triangle as a Positioning Tool to Simplify Prone Ankle Fracture Surgery
Authors: Hamid Kamran S. , Dekker Travis J. , White Peter W. , Adams Samuel B. 
Published: October 2016

Prone positioning affords significant benefits for the fixation of trimalleolar ankle fractures and has been the long-time standard for treatment of these injuries. However, 2 primary disadvantages hamper its utility. First, access to the medial ankle is impeded by the contralateral limb and inability to rotate the operative leg to the extent that is possible in other positions. Second, lateral fluoroscopic imaging of the ankle can be cumbersome and often necessitates physically elevating the ankle for a radiograph then placing it back on the operative table. We describe a simple and cost-conscious technique for overcoming these obstacles of prone positioning in ankle fracture surgery. Judicious placement of a radiolucent triangle under the nonoperative leg in the prone position allows for unobstructed access to the medial ankle in conjunction with simplified lateral fluoroscopic imaging. An alternative technique is to place the radiolucent triangle under the operative leg with the bed in reverse Trendelenberg. Surgeons should consider adding these positioning techniques to their operative armamentarium for usage in appropriate cases. Levels of Evidence: Level V
Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial
Authors: Raina D. B. , Gupta A. , Petersen M. M. , Hettwer W. , McNally M. , Tägil M. , Zheng M-H. , Kumar A. , Lidgren L. 
Published: October 2016

ObjectivesWe have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.Materials and MethodsWe seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.ResultsC2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage.ConclusionExtra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1.
The importance of organizing activities of the Turkish Cypriot Community in the process of becoming a state (1957-1960)
Authors: Koyuncu Mevlüt , Balıkçıoğlu Emrah 
Published: October 2016

In this study, organization process of the Turkish Cypriot Community between 1957 and 1960 was examined. This study claims that this process was important, because it formed the basis of Turkish Cypriots’ becoming a state.It can be said that there are two main views about organization process of Turkish Cypriots in researches which were examined for this study. Researchers such as Ahmet An and Niyazi Kızılyürek allege that this process was Turco-British collusion to divide Turkish and Greek Cypriots who had lived together peacefully for centuries. According to researchers such as Ahmet C. Gazioğlu and Ulvi Keser; Turkish Cypriots started an organization process to protect themselves from Greek Cypriots’ hostility and attacks. However, it seems that the relationship between organization process of the Turkish Cypriot Community and Turks’ becoming a state has not been handled yet.After the Great Britain took over the rule of Cyprus from the Ottoman Empire by the Cyprus Convention in 1878, the British established a Legislative Council. Greek Cypriots who desired to realize enosis (union with Greece) made attempts to pass enosis memorandums in the Council. On the contrary, Turkish Cypriots who saw union with Greece as a threat to their safety avoided these attempts with help of the British. Moreover, Turks published various newspapers and journals to voice their objections to enosis. Both these efforts and anti-Turkish feelings caused Greek Cypriots’ attacking Turkish Cypriots. In order to protect themselves from these attacks and conduct effective struggle against enosis, Turkish Cypriots set up assemblies, political parties, farmer and trade unions, social associations and armed organizations from 1918 to 1957. However, it was 1957 when these organization activities became continuous process. Hence the Turkish Cypriot Community was organized in terms of, military, administration, economy and culture during the period between 1957 and 1960. Turkish states which were founded between 1964 and 1983 were based on these organizations. Considering this fact, the study is composed of two main parts. The first part summarizes the organization efforts of the Turkish Cypriot Community between 1918 and 1957. The second part focuses on the organization process of the Turkish Cypriot Community between 1957 and 1960.
The effect of endurance exercise on intestinal integrity in well‐trained healthy men
Authors: JanssenDuijghuijsen Lonneke M. , Mensink Marco , Lenaerts Kaatje , Fiedorowicz Ewa ,   the Protégé study group, van Dartel Dorien A. M. , Mes Jurriaan J. , Luiking Yvette C. , Keijer Jaap , Wichers Harry J. , Witkamp Renger F. , van Norren Klaske 
Published: October 2016

AbstractExercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent endurance exercise in the glycogen‐depleted state can affect intestinal permeability toward small molecules and protein‐derived peptides in relation to markers of intestinal function. Eleven well‐trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual – glycogen depletion and endurance – exercise protocol (first protocol execution). The entire procedure was repeated 1 week later (second protocol execution). Intestinal permeability was measured as L/R ratio in 5 h urine and 1 h plasma. Five‐hour urine excretion of betacasomorphin‐7 (BCM7), postprandial plasma amino acid levels, plasma fatty acid binding protein 2 (FABP‐2), serum pre‐haptoglobin 2 (preHP2), plasma glucagon‐like peptide 2 (GLP2), serum calprotectin, and dipeptidylpeptidase‐4 (DPP4) activity were studied as markers for excretion, intestinal functioning and recovery, inflammation, and BCM7 breakdown activity, respectively. BCM7 levels in urine were increased following the dual exercise protocol, in the first as well as the second protocol execution, whereas 1 h‐plasma L/R ratio was increased only following the first exercise protocol execution. FABP2, preHP2, and GLP2 were not changed after exercise, whereas calprotectin increased. Plasma citrulline levels following casein ingestion (iAUC) did not increase after exercise, as opposed to resting conditions. Endurance exercise in the glycogen depleted state resulted in a clear increase of BCM7 accumulation in urine, independent of DPP4 activity and intestinal permeability. Therefore, strenuous exercise could have an effect on the amount of food‐derived bioactive peptides crossing the epithelial barrier. The health consequence of increased passage needs more in depth studies.
Removal of copper from copper-contaminated river water and aqueous solutions using Methylobacterium extorquens modified Erzurum clayey soil
Authors: Celebi Neslihan , Nadaroglu Hayrunnisa , Kalkan Ekrem , Kotan Recep 
Published: October 2016

Abstract
The objective of this study was to investigate the possibility of using natural and bacteria-modified Erzurum clayey soil with Methylobacterium extorquens as an alternative to high cost commercial adsorbent materials for the removal of copper from aqueous solution. The copper concentrations in the samples of the polluted river water and CuCl2 solutions treated by the natural and bacteria-modified Erzurum clayey soil (ECS) have been determined by spectrophotometric method. Firstly, the surface of ECS was modified with M. extorquens and surface functionality was increased. Then, the adsorption of Cu (II) from solution phases was studied with respect to varying metal concentration, pH, and temperature and agitation time. The maximum adsorption of Cu (II) for natural and bacteria-modified Erzurum clayey soil was observed at pH: 5.0. At different copper concentrations, copper adsorption analysis was performed on 1 g using clay soil or modified clay soil. Maximum adsorption of Cu (II) was obtained as 45.7 and 48.1 mg g-1 at initial concentration (50 mg/50 mL) and optimal conditions by natural and bacteria-modified clay soil, respectively. The copper concentration was decreased in the substantial amount of the leachates solutions of natural and bacteria-modified clay soil. Langmuir and Freundlich isotherms were used to describe the adsorption behavior of Cu (II) ions. The results showed that modified clay soil had a high level of adsorption capacity for copper ion. The various thermodynamic parameters such as ΔG°, ΔH° and ΔS° were analyzed to observe the nature of adsorption. The structural properties of the natural and bacteria-modified-ECS have been characterized by SEM, FTIR and XRD techniques. Consequently, it was concluded that the bacteria-modified clay soil could be successfully used for the removal of the copper ions from the aqueous solutions.
The influence of hydraulic loading on biofilm properties in a subsurface wastewater infiltration system
Authors: Zhang Liangbo , Yang Jian 
Published: October 2016

AbstractIn this study, a pilot-scale subsurface wastewater infiltration system (SWIS) was deployed to study landscape water treatment. The goal of the study was to investigate the effects of hydraulic loading on pollutant removal and the spatial distribution of biofilm properties in SWIS. Results showed that the efficiencies of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) removal degraded as hydraulic loading increased. Furthermore, quantities of the biofilm properties parameter s increased with the hydraulic loading. Polysaccharide and protein levels ranged from 560 to 1110 μg/g filler and 60 to 190 μg/g filler, respectively, at a hydraulic loading of 0.2 m/d. At a hydraulic loading of 0.4 m/d, the quantities of polysaccharide and protein ranged from 1200 to 3300 μg/g filler and 80 to 290 μg/g filler, respectively. Biofilm intensity and biofilm activity per unit weight decreased with the increase in hydraulic loading.