bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and translational pharmacology of the cathepsin K inhibitor odanacatib studied for osteoporosis
Authors: Stone Julie A. , McCrea Jacqueline B. , Witter Rose , Zajic Stefan , Stoch S. Aubrey 
Published: January 2019

Cathepsin K (CatK) is a cysteine protease abundantly expressed by osteoclasts and localized in the lysosomes and resorption lacunae of these cells. CatK is the principal enzyme responsible for the degradation of bone collagen. Odanacatib is a selective, reversible inhibitor of CatK at subnanomolar potency. The pharmacokinetics of odanacatib have been extensively studied and are similar in young healthy men, postmenopausal women and elderly men, and were qualitatively similar throughout Phase 1 development and in‐patient studies. Following 3 weeks of 50 mg once weekly dosing the geometric mean area under the curve from 0 to 168 hours was 41.1 μM h, the concentration at 168 hours was 126 nM and the harmonic mean apparent terminal half‐life was 84.8 hr. Odanacatib exposure increased in a less than dose proportional manner due to solubility limited absorption. It is estimated that approximately 70% of the absorbed dose of odanacatib is eliminated via metabolism, 20% is excreted as unchanged drug in the bile or faeces, and 10% is excreted as unchanged drug in the urine. The systemic clearance was low (approximately 13 mL/min). Odanacatib decreases the degradation of bone matrix proteins and reduces the efficiency of bone resorption with target engagement confirmed by a robust decrease in serum C‐telopeptides of type 1 collagen (approximately 60%), urinary aminoterminal crosslinked telopeptides of type 1 collagen to creatinine ratio (approximately 50%) and total urine deoxypyridinoline/Cr (approximately 30%), with an increase in serum cross‐linked carboxy‐terminal telopeptide of type 1 collagen (approximately 55%). The 50‐mg weekly dosing regimen evaluated in Phase 3 achieved near maximal reduction in bone resorption throughout the treatment period. The extensive clinical programme for odanacatib, together with more limited clinical experience with other CatK inhibitors (balicatib and ONO‐5334), provides important insights into the clinical pharmacology of CatK inhibition and the potential role of CatK in bone turnover and mineral homeostasis. Key findings include the ability of this mechanism to: (i) provide sustained reductions in resorption markers, increases in bone mineral density, and demonstrated fracture risk reduction; (ii) be associated with relative formation‐sparing effects such that sustained resorption reduction is achieved without accompanying meaningful reductions in bone formation; and (iii) lead to increases in osteoclast number as well as other osteoclast activity (including build‐up of CatK enzyme), which may yield transient increases in resorption following treatment discontinuation and the potential for nonmonotonic responses at subtherapeutic doses.
Long‐term survival rates of patients undergoing vitrectomy for diabetic retinopathy in an Australian population: a population‐based audit
Authors: Liu Ebony , Estevez Jose , Kaidonis Georgia , Hassall Mark , Phillips Russell , Raymond Grant , Saha Niladri , Wong George H.C. , Gilhotra Jagjit , Burdon Kathryn , Landers John , Henderson Tim , Newland Henry , Lake Stewart , Craig Jamie E. 
Published: January 2019

AbstractImportanceFive‐year survival rates in patients undergoing vitrectomy for diabetic retinopathy (DR) vary from 68% to 95%. No study has been conducted in an Australian population.BackgroundWe aimed to determine the survival rates of patients undergoing diabetic vitrectomy in an Australian population.DesignRetrospective audit, tertiary centre hospitals and private practices.ParticipantsAll individuals in South Australia and the Northern Territory who underwent their first vitrectomy for diabetic complications between January 1, 2007 and December 31, 2011.MethodsAn audit of all eligible participants has been completed previously. Survival status as of July 6, 2018 and cause of death were obtained using SA/NT DataLink. Kaplan‐Meier survival curves and multivariate cox‐regressions were used to analyse survival rates and identify risk factors for mortality.Main outcome measuresFive‐, seven‐ and nine‐year survival rates.ResultsThe 5‐, 7‐ and 9‐year survival rates were 84.4%, 77.9% and 74.7%, respectively. The most common cause of death was cardiovascular disease. Associated with increased mortality independent of age were Indigenous ethnicity (HR = 2.04, 95% confidence interval [CI]: 1.17‐3.57, P = 0.012), chronic renal failure (HR = 1.76, 95% CI: 1.07‐2.89, P = 0.026) and renal failure requiring dialysis (HR = 2.32, 95% CI: 1.25‐4.32, P = 0.008).Conclusions and relevanceLong‐term survival rates after diabetic vitrectomy in Australia are similar to rates reported in other populations. Indigenous ethnicity and chronic renal failure were the most significant factors associated with long‐term mortality. This information can guide allocation of future resources to improve the prognosis of these high risk groups.
Choroidal structure in subtypes of polypoidal choroidal vasculopathy determined by binarization of optical coherence tomographic images
Authors: Liu Bing , Zhang Xiongze , Mi Lan , Peng Yuting , Wen Feng 
Published: January 2019

AbstractImportanceChorodial structure in subtypes of polypoidal choroidal vasculopathy (PCV).BackgroundTo evaluate choroidal vascularity in the eyes of patients with PCV with and without choroidal vascular hyperpermeability (CVH).DesignA hospital‐based retrospective study.ParticipantsFifty‐eight PCV patients (28 with CVH; 30 without CVH) and 30 normal controls were included in this study.MethodsAll study subjects underwent spectral‐domain optical coherence tomography with enhanced depth imaging, and the choroidal images were binarized into the luminal area and stromal area.Main Outcome MeasuresChoroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT).ResultsCompared to normal controls, patients with PCV showed no obvious difference in SFCT (P = 0.510), but significantly lower CVI (P = 0.003). Among PCV patients, the CVI in eyes with CVH was significantly greater than that in those without CVH (65.78 ± 4.70 vs 62.28 ± 3.90; P = 0.002), and a significant difference in SFCT was also found between the two subtypes of PCV (340.8 ± 89.2 vs 250.4 ± 67.7; P < 0.001).Conclusions and RelevancePCV eyes with CVH have a greater CVI and a thicker SFCT than those without CVH. The significant differences in choroidal vascularity between the two subtypes of PCV may broaden our understanding of the pathogenesis of this disease and contribute to significant improvements in treatment.
The Liverpool Peritonsillar abscess Score: Development of a predictive score through a prospective multicentre observational study
Authors: Lau Andrew S. , Selwyn David M. , Yang Ding , Swainbank Liam , Ridley Paul , Carmichael Nicola , Metcalfe Christopher , Watson George , Emerson Hannah 
Published: January 2019

ObjectivesWhile uncommon in the population at large, peritonsillar abscess (PTA) is a common subject of ENT referrals. Missed or uncertain diagnosis is a source of concern for non‐specialist referrers. In line with the NHS England Second Sepsis Action Plan, we aimed to develop a predictive score for the presence of PTA. This would help to improve non‐specialist colleagues’ diagnostic certainty as well as to support ENT surgeons’ triage of these referrals.DesignProspective, multicentre observational study.SettingPrimary and secondary care.ParticipantsPatients >16 years with symptoms of sore throat.DataWe prospectively collected comprehensive data on patient demographics, symptoms and clinical status. We documented whether the patient had aspiration‐proven PTA or not. We performed binary logistic regression analysis, iterative development of a predictive score which we validated internally.Results100 patients were included (46 PTA and 54 tonsillitis). Five variables added significantly to the logistic regression model: unilateral sore throat; trismus; male gender; pharyngeal voice change; and uvular deviation. Using the odds ratio outputs, we developed the Liverpool Peritonsillar abscess Score (LPS) iteratively. We validated the latest (third) iteration of the LPS internally (ie, on the same sample), yielding sensitivity 96%; specificity 85%; positive predictive value 85%; and negative predictive value 96%. The area under the receiver operating characteristics (AUROC) curve was 0.970.ConclusionsWe have developed the first predictive score for PTA based on symptoms and signs that do not require the user to have specialist experience. Its high negative predictive value may be particularly helpful to non‐specialist colleagues.
Concomitant contact‐allergic reactions to iodopropynyl butylcarbamate and iodine
Authors: Vanhoutte Charlotte , Goossens An , Gilissen Liesbeth , Huygens Sarah , Vital‐Durand Dominique , Dendooven Ella , Aerts Olivier 
Published: January 2019

BackgroundIodopropynyl butylcarbamate (IPBC) is a broad‐spectrum preservative for use in several product types, including cosmetics, in which its concentrations have been limited by EU legislation because of concerns related to its iodine content and release, and the risk of subsequent iodine overdose.ObjectivesTo report on concomitant patch test reactions observed with iodine and IPBC in patients sensitized to iodine‐containing antiseptics.PatientsBetween 2012 and 2018, seven patients, six from Belgium and one from France, two suffering from acute dermatitis during surgical interventions, four from dermatitis caused by wound treatment, and one from occupational dermatitis, were shown to be sensitized to iodine and/or povidone‐iodine (PVP‐I), which was considered to be relevant for their dermatitis. All patients were coincidentally also patch tested with IPBC.ResultsAll patients showed positive patch test reactions to several other allergens, including IPBC. No relevance could be detected for IPBC.ConclusionsWe suspect that, notwithstanding the absence of firm evidence for IPBC being dehalogenated to produce free iodine in animals or in humans, the patch test reactions to IPBC in iodine‐allergic subjects were possibly caused by free iodine released from this preservative agent, thus underlining the EU restrictions regarding the use of this preservative in cosmetics.
Does Information Technology Substitute for or Complement Human Labor? A Dynamic Stratified Analysis on European Countries
Authors: Peng Gang , Zhang Dawei (David) 
Published: January 2019

ABSTRACTThe interaction between information technology (IT) and human labor in manufacturing and service provision has always been a topic of much debate. Anchored from the skill‐biased technological change theory and the organizational complementarity theory, this study proposes a dynamic stratified analysis and argues that the relationship between IT and labor is more nuanced than what has been conceptualized in prior literature. We find that IT can not only substitute for human labor but also can complement it—the exact nature depends on the skill levels of the labor. In addition, as the capability of IT continues to grow, the substitution/complementarity relationship between IT and labor evolves over time. We test our hypotheses using the EU KLEMS dataset covering 31 industries from 13 EU countries from year 1970 to 2005. The findings shed light on the nature of interaction between IT and human labor and contribute to both the information systems literature and the operations management literature by providing a deeper understanding on how IT can influence labor input, tasks, jobs, and productivity.
Clinical features of facioscapulohumeral muscular dystrophy 1 in childhood
Authors: Steel Dora , Main Marion , Manzur Adnan , Muntoni Francesco , Munot Pinki 
Published: January 2019

AimTo explore the clinical course of patients presenting with facioscapulohumeral dystrophy type 1 (FSHD1) in childhood, with a view to identifying areas where they differed from older patients and where extra support or monitoring might be required.MethodA retrospective case‐notes review of children with FSHD1 seen at a tertiary paediatric neuromuscular centre between 2002 and 2016 was performed. Data collected included age at and nature of presentation, path to diagnosis, genetic testing results, motor function, and occurrence of extramuscular features and complications.ResultsEighteen children (11 females, seven males; mean [SD] age at latest review 13y 10mo [3y 9mo], range 8–19y) from 16 families were identified. Age at onset of FSHD1 correlated with the size of deletion (r=0.81) and most presentations were in children either younger than 5 years or older than 10 years. Children with onset before 5 years were more likely to present with non‐muscular symptoms and to develop extramuscular pathology, including developmental and psychiatric issues, hearing or visual impairments, and problems involving respiratory function and nutrition. No cases of epilepsy or cardiac arrhythmia were identified but two children died.InterpretationThe complexity and severity of FSHD1 presenting in early childhood underlines the importance of a multidisciplinary approach to the disorder.What this paper adds

Young children often present with non‐muscular pathology in facioscapulohumeral dystrophy type 1 (FSHD1), especially hearing loss.

Age at onset in paediatric FSHD1 appears bimodal: under 5 years or in adolescence.

Prolonged delays to diagnosis are common.

Children with very early‐onset FSHD1 may require nutritional and/or respiratory support.

Developmental and psychiatric comorbidities are common.
Prevalence of metabolic syndrome and cardiovascular disease risk factors in adults with cerebral palsy
Authors: Heyn Patricia C , Tagawa Alex , Pan Zhaoxing , Thomas Sruthi , Carollo James J 
Published: January 2019

AimTo investigate the prevalence of metabolic syndrome and cardiovascular disease (CVD) risk factors and the association between common metabolic markers and Gross Motor Function Classification System (GMFCS) levels in ambulatory adults with cerebral palsy (CP).MethodMetabolic markers and GMFCS levels were evaluated in a cross‐sectional study of 70 ambulatory adults with CP (34 males, 36 females; mean age 24y 5mo [SD 5y 4mo], range 18y 6mo–48y 8mo) to determine the prevalence of metabolic syndrome and CVD risk factors, and were compared to age‐matched, population norms from the National Health and Nutrition Examination Survey (NHANES) registry. The Framingham Heart Study (FHS) CVD risk estimation was also used to evaluate an individual's risk for CVD.ResultsMetabolic syndrome was identified in 17.1% of the cohort, higher than the 10% in the NHANES registry. The FHS CVD 30‐year lipid and body mass index (BMI)‐based risk factor results showed that 20% to 40% of the cohort was at greater risk of developing CVD (BMI‐based: 39.7% ‘full’ CVD risk factor; lipid‐based: 26.5% ‘full’ CVD risk factor) as compared to the FHS normative population data. There was a positive correlation between GMFCS level, waist circumference (r=0.28, p=0.02), and waist‐to‐hip ratio (r=0.28, p=0.02).InterpretationAdults with CP are at higher risk of CVD and metabolic syndrome compared to the general population, which is probably because of impaired mobility.What this paper adds

Gross Motor Function Classification System levels can predict cardiovascular disease (CVD) risk factors in adults with cerebral palsy (CP).

Anthropometric measures are significant in predicting CVD risk factors in adults with CP.

Early CVD screening and ongoing risk factor monitoring are important in adults with CP.
One‐hour post‐load plasma glucose predicts progression to prediabetes in a multi‐ethnic cohort of obese youths
Authors: Tricò Domenico , Galderisi Alfonso , Mari Andrea , Santoro Nicola , Caprio Sonia 
Published: January 2019

AIMSOne‐hour post‐load hyperglycaemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1‐hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status of a multi‐ethnic cohort of youths with normal glucose tolerance (NGT).Materials and methodsA total of 202 obese youths with NGT (33.7% Caucasian, 31.1% Hispanic, 32.2% African American) underwent a 3‐hour OGTT at baseline and after a 2‐year follow‐up period. Whole‐body insulin sensitivity, insulin secretion, β‐cell function and insulin clearance were estimated by modeling plasma glucose, insulin and C‐peptide levels.ResultsObese youths with 1hPG ≥7.4 mmol/L (or 133 mg/dL; n = 83) exhibited higher body mass index (BMI), plasma triglycerides and fasting and post‐load glucose concentrations than individuals with 1hPG <7.4 mmol/L. Also, 1hPG ≥7.4 mmol/L was associated with a lower disposition index (DI) (P < 0.0001) and with alterations in whole‐body insulin sensitivity, β‐cell function and insulin clearance. Adolescents with 1hPG ≥7.4 mmol/L were approximately three times more likely to develop prediabetes (ie, impaired glucose tolerance and/or impaired fasting glucose) over time (OR, 2.92 [1.22‐6.98]; P = 0.02), independent of age, sex, race/ethnicity, BMI, insulin sensitivity, DI and plasma glucose concentrations. No differences emerged in the risk of prediabetes related to 1‐hour hyperglycaemia among different ethnic groups.ConclusionsA plasma glucose concentration ≥ 7.4 mmol/L at 1 hour during an OGTT is associated with a worse clinical and metabolic phenotype and may be an independent predictor of progression to prediabetes in obese youths with NGT.
Two conifer species native to Patagonia threatened by Phytophthora austrocedri
Authors: Taccari Leonardo E. , Greslebin Alina G. , Salgado Salomón María E. , Vélez María L. 
Published: January 2019

AbstractPhytophthora austrocedri is a pathogen of Austrocedrus chilensis causing “Mal del Ciprés” (cypress sickness) in Patagonia and killing Juniperus communis in Britain, along with other species in the Cupressaceae. The evident association of the pathogen with members of the Cupressaceae makes it necessary to study the susceptibility of other species related to A. chilensis to prevent the emergence of new diseases. The present study tested the pathogenicity of P. austrocedri to three native and endemic conifers in South America: Fitzroya cupressoides, Pilgerodendron uviferum and Araucaria araucana. The results showed that F. cupressoides and P. uviferum were highly susceptible to P. austrocedri. Since these are endangered tree species, the outcome of this study is crucial for governmental agencies, policymakers and stakeholders.
Single versus double‐unit transfusion: Safety and efficacy for patients with hematologic malignancies
Authors: Bowman Zelia , Fei Naomi , Ahn Janice , Wen Sijin , Cumpston Aaron , Shah Nilay , Craig Michael , Perrotta Peter L. , Kanate Abraham S. 
Published: January 2019

AbstractObjectivesAlthough hemoglobin thresholds for red blood cell (RBC) transfusion have decreased, double‐unit RBC transfusion practices persist. We studied the effects switching from predominantly double‐unit to single‐unit RBC transfusions had on utilization and clinical outcomes for malignant hematology patients.MethodsRetrospective chart review compared malignant hematology patients before and after implementing single‐unit RBC transfusion policy. Hemoglobin threshold was 8.0 g/dL for both groups. RBC utilization metrics included number of RBC units transfused, RBC units transfused per admission, and number of transfusion episodes. Clinical outcomes included length of stay, 30‐day mortality, and outpatient RBC transfusion 30‐days post‐discharge.ResultsBaseline hemoglobin was similar in both groups. The single‐unit group was transfused with fewer RBC units per admission (5.1 vs 4.5, P = 0.01) than the double‐unit group, but had more transfusion episodes per admission (4.1 vs 2.7, P < 0.001). After implementing single‐unit policy, a 29% reduction in RBC utilization was observed. Mean hemoglobin at discharge was lower in the single‐unit group (8.9 vs 9.5 g/dL, P = 0.005). No significant differences in length of stay or 30‐day mortality were observed.ConclusionTransfusing malignant hematology patients with single RBC units is safe and efficacious. Electronic provider order systems facilitating RBC transfusion requests provide excellent adherence to transfusion policy.
Insight into the complex pathophysiology of sickle cell anaemia and possible treatment
Authors: Piccin Andrea , Murphy Ciaran , Eakins Elva , Rondinelli Maria Beatrice , Daves Massimo , Vecchiato Cinzia , Wolf Dominik , Mc Mahon Corrina , Smith Owen P. 
Published: January 2019

AbstractSickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.
Improving the SVM gender classification accuracy using clustering and incremental learning
Authors: Dagher Issam , Azar Fady 
Published: January 2019

AbstractGender recognition has been playing a very important role in various applications such as human–computer interaction, surveillance, and security. Nonlinear support vector machines (SVMs) were investigated for the identification of gender using the Face Recognition Technology (FERET) image face database. It was shown that SVM classifiers outperform the traditional pattern classifiers (linear, quadratic, Fisher linear discriminant, and nearest neighbour). In this context, this paper aims to improve the SVM classification accuracy in the gender classification system and propose new models for a better performance. We have evaluated different SVM learning algorithms; the SVM‐radial basis function with a 5% outlier fraction outperformed other SVM classifiers. We have examined the effectiveness of different feature selection methods. AdaBoost performs better than the other feature selection methods in selecting the most discriminating features. We have proposed two classification methods that focus on training subsets of images among the training images. Method 1 combines the outcome of different classifiers based on different image subsets, whereas method 2 is based on clustering the training data and building a classifier for each cluster. Experimental results showed that both methods have increased the classification accuracy.