bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating Tissue Factor–Positive Cancers with Antibody–Drug Conjugates That Do Not Affect Blood Clotting
Authors: Theunissen Jan-Willem , Cai Allen G. , Bhatti Maryam M. , Cooper Anthony B. , Avery Andrew D. , Dorfman Ryan , Guelman Sebastian , Levashova Zoia , Migone Thi-Sau 
Published: August 2018

Abstract
The primary function of tissue factor (TF) resides in the vasculature as a cofactor of blood clotting; however, multiple solid tumors aberrantly express this transmembrane receptor on the cell surface. Here, we developed anti-TF antibody–drug conjugates (ADC) that did not interfere with the coagulation cascade and benchmarked them against previously developed anti-TF ADCs. After screening an affinity-matured antibody panel of diverse paratopes and affinities, we identified one primary paratope family that did not inhibit conversion of Factor X (FX) to activated Factor X (FXa) and did not affect conversion of prothrombin to thrombin. The rest of the antibody panel and previously developed anti-TF antibodies were found to perturb coagulation to varying degrees. To compare the anticancer activity of coagulation-inert and -inhibitory antibodies as ADCs, a selection of antibodies was conjugated to the prototypic cytotoxic agent monomethyl auristatin E (MMAE) through a protease-cleavable linker. The coagulation-inert and -inhibitory anti-TF ADCs both killed cancer cells effectively. Importantly, the coagulation-inert ADCs were as efficacious as tisotumab vedotin, a clinical stage ADC that affected blood clotting, including in patient-derived xenografts from three solid tumor indications with a need for new therapeutic treatments—squamous cell carcinoma of the head and neck (SCCHN), ovarian, and gastric adenocarcinoma. Furthermore, a subset of the anti-TF antibodies could also be considered for the treatment of other diseases associated with upregulation of membranous TF expression, such as macular degeneration. Mol Cancer Ther; 17(11); 2412–26. ©2018 AACR.
Large abnormal peak on capillary zone electrophoresis due to contrast agent
Authors: Wheeler Rachel D , Zhang Liqun , Sheldon Joanna 
Published: August 2018

Background Some iodinated radio-contrast media absorb ultraviolet light and can therefore be detected by capillary zone electrophoresis. If seen, these peaks are typically small with ‘quantifications’ of below 5 g/L. Here, we describe the detection of a large peak on capillary zone electrophoresis that was due to the radio-contrast agent, Omnipaque™. Methods Serum from a patient was analysed by capillary zone electrophoresis, and the IgG, IgA, IgM and total protein concentrations were measured. The serum sample was further analysed by gel electrophoresis and immunofixation. Results Capillary zone electrophoresis results for the serum sample showed a large peak with a concentration high enough to warrant urgent investigation. However, careful interpretation alongside the serum immunoglobulin concentrations and total protein concentration showed that the abnormal peak was a pseudoparaprotein rather than a monoclonal immunoglobulin. This was confirmed by analysis with gel electrophoresis and also serum immunofixation. The patient had had a CT angiogram with the radio-contrast agent Omnipaque™; addition of Omnipaque™ to a normal serum sample gave a peak with comparable mobility to the pseudoparaprotein in the patient’s serum. Conclusions Pseudoparaproteins can appear as a large band on capillary zone electrophoresis. This case highlights the importance of a laboratory process that detects significant electrophoretic abnormalities promptly and interprets them in the context of the immunoglobulin concentrations. This should avoid incorrect reporting of pseudoparaproteins which could result in the patient having unnecessary investigations.
The effectiveness of a routine versus an extensive laboratory analysis in the diagnosis of anaemia in general practice
Authors: Schop Annemarie , Kip Michelle MA , Stouten Karlijn , Dekker Soraya , Riedl Jurgen , van Houten Ron J , van Rosmalen Joost , Dinant Geert-Jan , IJzerman Maarten J , Koffijberg Hendrik , Bindels Patrick JE , Kusters Ron , Levin Mark-David 
Published: August 2018

Background We investigated the percentage of patients diagnosed with the correct underlying cause of anaemia by general practitioners when using an extensive versus a routine laboratory work-up. Methods An online survey was distributed among 836 general practitioners. The survey consisted of six cases, selected from an existing cohort of anaemia patients ( n = 3325). In three cases, general practitioners were asked to select the laboratory tests for further diagnostic examination from a list of 14 parameters (i.e. routine work-up). In the other three cases, general practitioners were presented with all 14 laboratory test results available (i.e. extensive work-up). General practitioners were asked to determine the underlying cause of anaemia in all six cases based on the test results, and these answers were compared with the answers of an expert panel. Results A total of 139 general practitioners (partly) responded to the survey (17%). The general practitioners were able to determine the underlying cause of anaemia in 53% of cases based on the routine work-up, whereas 62% of cases could be diagnosed using an extensive work-up ( P = 0.007). In addition, the probability of a correct diagnosis decreased with the patient’s age and was also affected by the underlying cause itself, with anaemia of chronic disease being hardest to diagnose ( P = 0.003). Conclusion The use of an extensive laboratory work-up in patients with newly diagnosed anaemia is expected to increase the percentage of correct underlying causes established by general practitioners. Since the underlying cause can still not be established in 31.3% of anaemia patients, further research is necessary.
Predictive role of tear protein expression in the early diagnosis of Sjögren’s syndrome
Authors: Versura Piera , Giannaccare Giuseppe , Vukatana Gentiana , Mulè Rita , Malavolta Nazzarena , Campos Emilio C 
Published: August 2018

Background The contribution of tear protein expression in patients with presumed diagnosis of Sjögren syndrome is underestimated. We aimed to evaluate the role of tear proteins in the Sjögren syndrome early diagnosis. Methods Charts from 110 patients suspected of Sjögren syndrome were analysed and the subsequent diagnosis retrieved. Subjective symptoms (ocular surface disease index, OSDI), tear film break-up time (TFBUT), Schirmer test, Jones test, tear clearance (TC), corneal (NEI score) and conjunctival staining (van Bjerstelveldt score), esthesiometry, cytology, tear protein analysis (total protein [TP] content, lysozyme-C [LYS-C], lactoferrin [LACTO], lipocalin-1 [LIPOC-1] and albumin [ALB]) were analysed. The diagnostic performance with area under the curve (AUC) and odds ratio (OR) for each parameter were calculated. Results Thirty-five patients (31.8%) had been diagnosed as affected by Sjögren syndrome. Clinical tests showed lower diagnostic performance (OSDI > 44 [AUC 0.57], Schirmer ≤ 5 mm [0.59], TFBUT ≤ 3 s [0.72], TC > 1/16 [0.68], Jones ≤ 4 mm [0.68], corneal staining > 2 [0.51], conjunctival staining > 2 [0.78]) compared with tear proteins (LYS-C ≤ 1.5 mg/mL [0.79], LACTO ≤ 20% [0.94], LIPOC-1 ≤ 10% [0.89], ALB ≥ 15% [0.79]). LYS-C, LACTO, LIPOC-1 and ALB showed a significant association in predicting Sjögren syndrome vs. not-Sjögren syndrome dry eye (OR, respectively, 4.9, 5.5, 7.2, 6.7). Conclusions Tear proteins’ concentrations showed a significant higher accuracy compared with the traditional ocular clinical tests for reaching Sjögren syndrome’s diagnosis. In particular, LACTO and LIPOC-1 provided an excellent diagnostic performance and thus could likely be considered promising biomarkers of Sjögren syndrome.
Valid analytical performance specifications for combined analytical bias and imprecision for the use of common reference intervals
Authors: Hyltoft Petersen Per , Lund Flemming , Fraser Callum G , Sandberg Sverre , Sölétormos György 
Published: August 2018

Background Many clinical decisions are based on comparison of patient results with reference intervals. Therefore, an estimation of the analytical performance specifications for the quality that would be required to allow sharing common reference intervals is needed. The International Federation of Clinical Chemistry (IFCC) recommended a minimum of 120 reference individuals to establish reference intervals. This number implies a certain level of quality, which could then be used for defining analytical performance specifications as the maximum combination of analytical bias and imprecision required for sharing common reference intervals, the aim of this investigation. Methods Two methods were investigated for defining the maximum combination of analytical bias and imprecision that would give the same quality of common reference intervals as the IFCC recommendation. Method 1 is based on a formula for the combination of analytical bias and imprecision and Method 2 is based on the Microsoft Excel formula NORMINV including the fractional probability of reference individuals outside each limit and the Gaussian variables of mean and standard deviation. The combinations of normalized bias and imprecision are illustrated for both methods. The formulae are identical for Gaussian and log-Gaussian distributions. Results Method 2 gives the correct results with a constant percentage of 4.4% for all combinations of bias and imprecision. Conclusion The Microsoft Excel formula NORMINV is useful for the estimation of analytical performance specifications for both Gaussian and log-Gaussian distributions of reference intervals.
Unwanted road to anaemia in transthyretin familial amyloid polyneuropathy may continue irrespective of tafamidis treatment
Authors: Ikeda Tokunori , Masuda Teruaki , Ueda Mitsuharu , Yamashita Taro , Misumi Yohei , Shinriki Satoru , Ando Yukio 
Published: August 2018

Background This retrospective longitudinal study was performed to determine whether tafamidis treatment leads to improvements in commonly used blood data for transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods Commonly used blood data (complete blood count [including a haemogram], total protein, albumin, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, total bilirubin [T-Bil], creatine kinase, choline esterase, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, estimated glomerular filtration rate [eGFR], serum amyloid A protein, TTR, haemoglobin A1c, free triiodothyronine [FT3] and free thyroxine [FT4]) were investigated in 33 TTR-FAP patients. These values included longitudinal data at three time points: six months before or after tafamidis treatment and one year after tafamidis treatment. Longitudinal changes in each blood item were examined using a linear mixed model, adjusting for age at starting tafamidis, sex, TTR-FAP stage and value before tafamidis treatment. Results Our results show elevated TTR concentrations after tafamidis treatment. In contrast, haemoglobin, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, mean platelet volume, platelet distribution width, T-Bil, eGFR, FT3 and FT4, gradually decreased through a reference range. There were no characteristic observations in any other items. TTR binds to thyroid hormone; therefore, FT3 and FT4 decreased in inverse proportion to increased TTR concentrations. Conclusion Unfortunately, progression to anaemia may occur regardless of tafamidis treatment. Because anaemia is sometimes present in TTR-FAP, attention should be paid to longitudinal changes in commonly used blood data, irrespective of tafamidis treatment.
Difference of seasonal variation between glycated albumin and glycated haemoglobin
Authors: Tanaka Karin , Meguro Shu , Tanaka Masami , Irie Junichiro , Saisho Yoshifumi , Itoh Hiroshi 
Published: August 2018

Background Glycated albumin reflects 2–3-week glycaemic controls, and in addition to glycated haemoglobin, it has been used as a glycaemic control indicator. We presumed that glycated albumin also has seasonal variations and is related to temperature, similar to glycated haemoglobin. Methods The subjects were diabetic outpatients from April 2007 to March 2013. This resulted in the enrolment of 2246 subjects and the collection of a total of 53,968 measurements. Mean glycated haemoglobin, glycated albumin, and plasma glucose were calculated for each month over six years. The associations of the measures with each other and the average temperature for each month in Tokyo were assessed using Spearman rank correlation coefficients. Results Plasma glucose was highest in January and lowest in May. Glycated haemoglobin was highest in March and lowest in September. Glycated albumin was highest in May and lowest in December. Glycated albumin tended to have a disjunction with plasma glucose in winter. Glycated haemoglobin had seasonal variation, but glycated albumin did not. Plasma glucose and glycated haemoglobin showed significant negative correlations with temperature (rs = −0.359, P < 0.001, rs = −0.449, P < 0.001, respectively), but glycated albumin did not. However, glycated albumin was inter-correlated with plasma glucose (rs = 0.396, P < 0.001) and glycated haemoglobin (rs = 0.685, P < 0.001), and glycated haemoglobin was inter-correlated with plasma glucose (rs = 0.465, P < 0.001). Conclusion Glycated albumin and glycated haemoglobin showed different seasonal variations from each other over the six-year study period. Thus, further studies to identify factors that contribute to glycated albumin are needed.
Post hoc analysis of plasma amino acid profiles: towards a specific pattern in autism spectrum disorder and intellectual disability
Authors: Delaye Jean-Baptiste , Patin Franck , Lagrue Emmanuelle , Le Tilly Olivier , Bruno Clement , Vuillaume Marie-Laure , Raynaud Martine , Benz-De Bretagne Isabelle , Laumonnier Frederic , Vourc’h Patrick , Andres Christian , Blasco Helene 
Published: August 2018

ObjectivesAutism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30).MethodsWe performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers.ResultsMultivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P < 0.0003). Univariate analysis showed that autism spectrum disorder and intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P < 0.0001 and P = 0.0002, respectively) and serine ( P = 0.002 for both) concentrations. The multivariate model ( P < 6.12.10−7) to discriminate between autism spectrum disorders and intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002).ConclusionsWe revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.
Urban–rural disparity in colorectal cancer incidence and increasing trend in relation to socioeconomic development and urbanization in China
Authors: Wen Denggui , Zou Wendi , Wen Xiaoduo , Yang Yi , Chen Yuetong , He Yutong , Wang Guiying , Shan Baoen 
Published: August 2018

Objective To study urban–rural disparity in colorectal cancer incidence and the increasing trend in relation to rapid socioeconomic development and urbanization in China. Methods We compared the age-standardized incidence rates (ASRs) of colorectal cancer between rural and urban areas in China in 2012 and analyzed the trend in Shexian County for 2000–2015 using population-based tumor registration data collected in Shijiazhuang city (2012) and Shexian County (2000–2015). Results The ASRs of colorectal cancer in Shijiazhuang (urban) were considerably higher than in Shexian (rural) in both men (22.8 vs. 11.9/100,000) and women (15.0 vs. 9.3/100,000). The difference was similar to that between countries with high and medium human development indices according to GLOBOCAN 2012. In trend analysis, the biennial ASR in Shexian increased from 6.6 in 2000–2001 to 15.9/100,000 in 2014–2015 in men (averaged biennial percent change (ABPC) = +6.0%), and from 4.0 to 11.7/100,000 in women (ABPC=+5.5%). Conclusions The incidence of colorectal cancer in China is rising in parallel with socioeconomic development and urbanization. Integrated efforts should be made to reduce the incidences of overweight and obesity in society to help prevent this increase.
Median effective volume of ropivacaine 0.5% for ultrasound-guided adductor canal block
Authors: Tao Yan , Zheng Shao-qiang , Xu Tao , Wang Geng , Wang Yun , Wu An-shi , Yue Yun 
Published: August 2018

Objective This study aimed to identify the median effective volume of ropivacaine 0.5% for ultrasound-guided adductor canal block (ACB). Methods Thirty-two patients received ultrasound-guided ACB for knee arthroscopic meniscectomy. The criterion for successful ACB was the loss of pinprick sensation in the saphenous area (medial knee, leg, and foot). The volume of ropivacaine 0.5% in each case was determined using the up-down method and used for calculating the median effective dose. Results The mean age, weight, and height of patients were 28.6 ± 7.1 years, 68.2 ± 10.6 kg, and 172.5 ± 6.4 cm, respectively. Among patients who received 18- and 15-mL doses, ACB was successful in all four cases. Among patients who received a 12-mL dose, ACB was effective in eight and ineffective in two cases. Among patients who received a 10-mL dose, ACB was successful in six and unsuccessful in seven cases. In patients who received an 8-mL dose, ACB was ineffective in all five cases. The median effective volume of ropivacaine 0.5% was 10.4 mL (95% confidence interval, 9.1–11.4 mL). In all effective cases, the median quadriceps strength was grade 5. Conclusions The median effective volume of ropivacaine 0.5% is 10.4 mL for ultrasound-guided ACB.
Low Accuracy of Diagnostic Codes to Identify Anterior Cruciate Ligament Tear in Orthopaedic Database Research
Authors: Sanders Thomas L. , Pareek Ayoosh , Desai Vishal S. , Hewett Timothy E. , Levy Bruce A. , Stuart Michael J. , Dahm Diane L. , Krych Aaron J. 
Published: August 2018

Background: Database research is being used in orthopaedic literature with increased regularity. The main limitation of database research is the absence of diagnosis and treatment verification afforded by medical chart review. This absence may limit the accuracy of some conclusions and recommendations produced by database research. Hypothesis/Purpose: The purpose was to describe the accuracy of 1 database (Rochester Epidemiology Project) used in orthopaedic research to detect isolated anterior cruciate ligament (ACL) tears and to discuss the limitations of database research. It was hypothesized that diagnostic codes alone are unlikely to be accurate in identifying patients with ACL tears. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A population-based historical cohort study was performed with the Rochester Epidemiology Project database. All subjects had International Classification of Diseases, Ninth Revision, diagnosis codes consistent with ACL tears between January 1, 1990, and December 31, 2010. The medical records of all subjects were reviewed in detail to confirm the accuracy of diagnosis and gather data on injury type, laterality, associated meniscal injuries, magnetic resonance imaging findings, and treatment details. Results: A total of 3494 patients had codes consistent with ACL tears, and 2288 of them were confirmed through chart review to have an isolated ACL tear (65.5%). Among these were 1841 patients (52.7%) with an ACL tear within 1 year of injury and an additional 447 (12.8%) with an ACL tear >1 year from injury. Thirty-nine patients (1.1%) had a partial ACL tear diagnosed on magnetic resonance imaging, 48 (1.4%) had an isolated posterior cruciate ligament tear, and 22 (0.6%) had a combined ACL–posterior cruciate ligament injury. Twenty-four patients (0.7%) had ACL reconstruction before the study period. The remaining 1073 patients (30.7%) had diagnostic codes consistent with an ACL tear but did not have a cruciate ligament injury. Conclusion: This study demonstrates low accuracy with the use of diagnostic codes alone to identify an ACL tear. Database studies offer unique benefits to the medical literature, but the inherent limitations should be taken into account when these data are used to counsel patients, dictate clinical management, or make health care policy decisions. Information from a health care database is most accurate when accompanied by verification of diagnosis, treatment, and outcomes with medical chart review.