bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into origins, mechanisms, and utility of DNA methylation in B-cell malignancies
Authors: Oakes Christopher C. , Martin-Subero Jose I. 
Published: July 2018

AbstractUnderstanding how tumor cells fundamentally alter their identity is critical to identify specific vulnerabilities for use in precision medicine. In B-cell malignancy, knowledge of genetic changes has resulted in great gains in our understanding of the biology of tumor cells, impacting diagnosis, prognosis, and treatment. Despite this knowledge, much remains to be explained as genetic events do not completely explain clinical behavior and outcomes. Many patients lack recurrent driver mutations, and said drivers can persist in nonmalignant cells of healthy individuals remaining cancer-free for decades. Epigenetics has emerged as a valuable avenue to further explain tumor phenotypes. The epigenetic landscape is the software that powers and stabilizes cellular identity by abridging a broad genome into the essential information required per cell. A genome-level view of B-cell malignancies reveals complex but recurrent epigenetic patterns that define tumor types and subtypes, permitting high-resolution classification and novel insight into tumor-specific mechanisms. Epigenetic alterations are guided by distinct cellular processes, such as polycomb-based silencing, transcription, signaling pathways, and transcription factor activity, and involve B-cell-specific aspects, such as activation-induced cytidine deaminase activity and germinal center–specific events. Armed with a detailed knowledge of the epigenetic events that occur across the spectrum of B-cell differentiation, B-cell tumor–specific aberrations can be detected with improved accuracy and serve as a model for identification of tumor-specific events in cancer. Insight gained through recent efforts may prove valuable in guiding the use of both epigenetic- and nonepigenetic-based therapies.
The frequency of post‐traumatic stress disorder symptoms in athletes with and without sports related concussion
Authors: Brassil Heather E. , Salvatore Anthony P. 
Published: July 2018

AbstractBackgroundPurpose of this study is to investigate the presence and frequency of post‐traumatic stress disorder (PTSD) symptoms in post‐concussed (PC) athletes compared to a group of healthy control (HC) athletes.Research design and methodA pre and post‐test group design was used to compare a post‐concussed group to a matched healthy control group of athletes. An archival database which included PC (n = 62) and HC (n = 62) participants matched on age, years of education and gender who completed a test battery at baseline and post injury, The test battery was comprised of a neurocognitive assessment, self‐reported symptom inventory and PTSD symptom questionnaire. Post‐concussion assessment was obtained within 0–13 days post‐injury.ResultsPTSD symptom scores were greater in PC post injury group (Mdn = 0) than for the HC group (Mdn = 0.0), U = 1282.0, p = 0.000, r = 0.34. A Wilcoxon Signed‐ranks test indicated that PTSD symptom scores post‐injury (Mdn = 0) were significantly higher than pre‐injury (Mdn = 0), Z = − 2.75, p = 0.000, r = 0.35. Within the PC post injury group athletes having “difficulty sleeping” was the highest reported symptom an average of 25.8% followed by “avoiding similar situations” at an average of 19.4%. “Having trouble keeping thoughts of incident out of your head” was reported at an average of 17.7% and “flashbacks” were reported at an average of 12.9%. “Nightmares” and “feeling numb and detached” were reported at an average of 8.1 and 6.5% respectively.ConclusionAthletes who reported no PTSD symptoms prior to sports related concussion do exhibit symptoms of PTSD. Providing a PTSD symptom questionnaire may provide a more comprehensive treatment plan for PC post injury athletes who may be at risk of chronic PTSD symptoms.
Actionable Gene Alterations in an Asian Population With Triple-Negative Breast Cancer
Authors: Nagahashi Masayuki , Ling YiWei , Hayashida Tetsu , Kitagawa Yuko , Futamura Manabu , Yoshida Kazuhiro , Kuwayama Takashi , Nakamura Seigo , Toshikawa Chie , Yamauchi Hideko , Yamauchi Teruo , Kaneko Koji , Kanbayashi Chizuko , Sato Nobuaki , Miyoshi Yasuo , Tsuchida Junko , Nakajima Masato , Shimada Yoshifumi , Ichikawa Hiroshi , Lyle Stephen , Takabe Kazuaki , Okuda Shujiro , Wakai Toshifumi 
Published: July 2018

Purpose It has been suggested that the biologic characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to occur at a higher incidence in Japan than in the United States. However, most genomic studies of these tumors are from Western countries, and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96%) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35 of 53) of Japanese patients, as well as 66.7% (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration–approved drug. Conclusion Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.
Translating Gene Signatures Into a Pathologic Feature: Tumor Necrosis Predicts Disease Relapse in Operable and Stage I Lung Adenocarcinoma
Authors: Lin Emily Pei-Ying , Hsiao Tzu-Hung , Lu Jo-yang , Wong Siao-Han , Lu Tzu-Pin , Peck Konan , Takahashi Takashi , Yang Pan-Chyr 
Published: July 2018

Purpose The high 5-year disease relapse rate in patients with stage I lung adenocarcinoma indicates the need for additional risk stratification parameters. This study assessed whether gene signatures translate into a pathologic feature for better disease stratification. Materials and Methods The mutual interdependence and risk stratification power of three gene signatures, cell cycle, hypoxia, and mammalian target of rapamycin (mTOR), were investigated in nine cohorts of patients with lung adenocarcinoma and five cohorts of patients with lung squamous cell carcinoma. The translation from gene signatures to a pathologic feature, tumor necrosis, was validated in The Cancer Genome Atlas lung adenocarcinoma cohort. The translation of signature score to pathway activity was further investigated by integrative analyses using The Cancer Genome Atlas and The Cancer Protein Atlas lung adenocarcinoma data sets. Results The results showed that the three gene signatures were mutually interdependent in lung adenocarcinoma but not in lung squamous cell carcinoma. The signature activities were higher in necrosis-positive tumors than in necrosis-negative tumors. The signature score correlated with the expression level of the representative protein that implicated the activity of each pathway. These signatures stratified patients with operable and stage I lung adenocarcinomas into different risk groups independent of age and stage. Furthermore, the signatures translated to a pathologic feature, tumor necrosis, which predicted shorter overall and relapse-free survival in patients with operable and stage I lung adenocarcinomas. Conclusion This study showed that gene signatures could translate into a pathologic feature, tumor necrosis, with risk stratification ability in patients with operable and stage I lung adenocarcinomas.
Inventory Control and Delivery Time Quotation for Assembly Supply Chains
Authors: Chen Shi , Moinzadeh Kamran 
Published: July 2018

We study an inventory system involving a contractor, who provides quotations of delivery times to customers, and suppliers, who stock prefabricated modules that the contractor will use to complete orders. The customers’ decisions on whether to wait or leave depend on the quotations. This is an assembly system with partial lost sales, where the interaction between the quotation policy and the inventory policy is complicated. We consider either a uniform or an adaptive quotation policy and either an independent or a modified S policy to control the inventory. Under the independent S policy, we show that the multiple-supplier system can be converted into a one-supplier system, which enables us to devise an efficient simulation algorithm to identify the optimal parameters of this policy. Under the modified S policy, the suppliers can be rearranged into a serial system, but given the tedious computational nature of the modified S policy, we propose a dynamic programming–based heuristic, which is efficient and accurate, to identify the optimal parameters of this policy. Finally, we consider the decentralized setting, for which we propose a coordination mechanism that requires the contractor to impose a penalty for the suppliers’ stockouts and to provide a subsidy for the suppliers’ inventory. The online appendix is available at https://doi.org/10.1287/opre.2017.1704 .
Public Warnings in Counterterrorism Operations: Managing the “Cry-Wolf” Effect When Facing a Strategic Adversary
Authors: Bakshi Nitin , Pinker Edieal 
Published: July 2018

Public warnings have the potential to mitigate the threat from terrorism: the public is alerted, and in response, the terrorist may defer his attack. Paradoxically, warnings can be a victim of their own success. The absence of an attack may be misconstrued by the warning recipients as a false alarm, leading to warning fatigue and a dampened response to future warnings—also referred to as the “cry-wolf” effect. To capture this phenomenon and examine its implications, we model the interaction between the defender and the terrorist using a dynamic game-theoretic framework. Our equilibrium results suggest that absent any political gamesmanship or incompetence, the prospect of false alarms can lead to either lengthy stretches of sustained warning, or more attacks at lower warning levels. Furthermore, we recommend that warnings and security deployment ought to be decoupled and treated as independent levers. By studying how the equilibrium shifts with changes to the parameter regime, we find that an increase in the terrorist’s “readiness” can result in a lower frequency of terrorist attacks; and a rise in the cost of issuing warnings can induce more frequent warnings. The e-companion is available at https://doi.org/10.1287/opre.2018.1721 .
Estratégias sociais nas festas de São Sebastião: o exemplo do arrematador José Antônio de Freitas Guimarães no Rio de Janeiro (1795-1810)
Authors: Bellens Porto Maria Beatriz Gomes 
Published: July 2018

Resumo: A presente pesquisa tem como objetivo abordar as estratégias de parte da elite do Rio de Janeiro colonial ao buscar na administração pública, e na religiosidade, caminhos para se manter na hierarquia social da cultura política da sociedade de Antigo Regime. Um desses lugares era o Senado da Câmara do Rio de Janeiro, que ao administrar a festa de São Sebastião e seu oitavário (oito dias de festa), utilizava um sistema de arrematação no qual indivíduos forneciam os itens necessários para a celebração e depois cobravam exatamente o seu valor para os camarários, na busca por honra e prestígio, sendo José Antônio de Freitas Guimarães o mais regular e maior arrematador entre os anos de 1795 a 1810.Abstract: The present research has the purpose of approaching the strategies of part the elite in colonial Rio de Janeiro, as they sought ways to maintain their places in the social hierarchy of the Old Regime city, through the public administration and religiosity. One of those places was the City Council of Rio de Janeiro, which used to organize Saint Sebastian's Feast Day and its Octave (eight consecutive days of celebration), and used a system of public auctions where individuals would supply the city with the necessary items for the celebrations and then charge the Council at cost, in pursuit of honor and prestige. José Antônio de Freitas was the most frequent bidder from 1795 to 1810.
Overestimation of Hypoglycemia in Infants with a High Hematocrit
Authors: Kemperman Hans , van Solinge Wouter W , de Vooght Karen M K 
Published: July 2018

Abstract

Background
In neonates, hypoglycemia is an emergency condition requiring urgent treatment. Therefore, rapid and reliable blood glucose measurements are necessary. However, this step has been proven difficult because of both analytical and preanalytical variables. In our children's hospital, we incidentally observed cases of hypoglycemia that were not in line with the clinical picture of the infants. Remarkably, most of these infants had a high hematocrit.

Methods
Glucose concentrations were determined in blood samples from healthy participants that were collected in Li-heparin capillary and pediatric tubes. The effect of hematocrit on glucose consumption over time was studied by artificially increasing sample hematocrits. To study the effect of sample cooling, glucose concentrations were followed over time in samples stored at room temperature and on ice.

Results
In all samples, glucose concentrations declined with time. This effect was most dramatic [up to 18 mg/dL (1 mmol/L) in the first 30 min] in samples with high hematocrits and collected in capillary tubes. Cooling of samples clearly reduced glucose consumption; however, this was not evident in the first 30 min.

Conclusions
Overestimation of hypoglycemia in infants must be considered if samples are not centrifuged or are not analyzed immediately after sampling. The extent of overestimation is more pronounced in samples with a high hematocrit, collected in capillary tubes. Cooling of samples does not prevent glucose consumption in vitro during the first 30 min. These results emphasize that, for glucose analysis, prompt handling of samples of newborns with a high hematocrit is necessary.
Utility of Antinuclear Antibody Screening by Various Methods in a Clinical Laboratory Patient Cohort
Authors: Deng Xiaoli , Peters Brian , Ettore Michael W , Ashworth Judy , Brunelle Lynn A , Crowson Cynthia S , Moder Kevin G , Snyder Melissa R 
Published: July 2018

Abstract

Background
Antinuclear antibody (ANA)5 testing is routinely performed during evaluation of patients with a suspected connective tissue disease (CTD), yet the question of which method is most appropriate remains controversial. The purpose of this study was to evaluate the clinical utility of ANA testing by an enzyme immunoassay (EIA), an immunofluorescence assay (IFA), and a multiplex immunoassay (MIA) in a routine laboratory population.

Methods
Samples (n = 1000) were collected from specimens submitted for ANA testing by EIA (Bio-Rad). All samples were subsequently analyzed by IFA (Zeus) and MIA (Bio-Rad). The sample cohort was weighted to represent the routine testing population. Diagnostic information was obtained by chart review.

Results
For the diagnosis of a CTD, ROC curve analysis demonstrated no significant differences between IFA (area under the curve 0.81) and EIA (0.84) (P = 0.25), with overlay of a single point for the MIA. When normalized to a specificity of approximately 90%, the sensitivities of the MIA, EIA, and IFA were 67%, 67%, and 56%, respectively. By varying the clinical cutoff, the IFA could achieve the highest sensitivity of 94%; however, the corresponding specificity was only 43%. In contrast, a strongly positive EIA had a specificity of 97%, although, at this cutoff, the sensitivity was only 40%.

Conclusions
Although the overall diagnostic performance of the IFA, EIA, and MIA were not statistically different, the clinical sensitivity and specificity varied dramatically based on the positive/negative cutoff. Knowledge about the performance characteristics of each method will significantly aid in the interpretation of ANA testing.
Prednisolone Replacement Therapy Mimics the Circadian Rhythm More Closely Than Other Glucocorticoids
Authors: Williams Emma L , Choudhury Sirazum , Tan Tricia , Meeran Karim 
Published: July 2018

Abstract

Background
This study examined the pharmacokinetic profile of prednisolone.

Methods
Using a newly developed ultra-performance liquid chromatography MS/MS method, prednisolone profiles in healthy volunteers and patients with adrenal insufficiency already treated with prednisolone were prospectively analyzed in a tertiary center.

Results
Twelve prednisolone day curves were analyzed. Six patients with secondary adrenal insufficiency provided 7 curves and 3 healthy volunteers provided 5 curves, 1 of which was with the prednisolone administered in divided doses. The mean prednisolone dose required for adequate replacement in hypoadrenal patients was 3.86 mg. The overall mean maximal serum concentration (C max) was 114.0 μg/L and was achieved at an average time to maximal concentration (T max) of 1.43 h. Total glucocorticoid exposure was represented by the mean area under the curve to 24 h (AUC0–24h), which was 518.2 μg|·|h/L. Splitting the dose substantially increased the total glucocorticoid exposure.

Conclusions
The pharmacokinetic profile of prednisolone is similar to the published profile of dual-release hydrocortisone. Once-daily prednisolone can thus be used as a replacement for hydrocortisone. Further studies need to be carried out to accurately calculate an equivalent replacement dose. Prednisolone levels are a useful adjunct to dose adjustment when low doses are being used for replacement.
Nuclear Magnetic Resonance–Based Metabolomics of Human Filtered Serum: A Great White Hope in Appraisal of Chronic Stable Angina and Myocardial Infarction
Authors: Gupta Ashish , Kumar Sudeep , Kashyap Shiridhar , Kumar Deepak , Kapoor Aditya 
Published: July 2018

Abstract

Background
Biochemical detection of chronic stable angina (CSA) and myocardial infarction (MI) are challenging. To address the shortcomings of the conventional biochemical approach for detection of MI, we applied serum lacking proteins and lipoprotein-based metabolomics in an approach using proton nuclear magnetic resonance (1H NMR) spectroscopy for screening of coronary artery disease (CAD) and especially MI. Our aim was to discover differential biomarkers among subjects with normal coronary (NC), CSA, and MI.

Methods
The study comprised serum samples from nondiabetic angiographically proven CAD [CSA (n = 88), MI (n = 90)] and NC (n = 55). 1H NMR spectroscopy was used to acquire metabolomics data. Clinical variables such as troponin I (TI), lactate dehydrogenase (LD), creatine kinase (CK, CK-MB, CK-MM), serum creatinine, and lipid profiles were also measured in all subjects. Metabolomic data and clinical measures were appraised separately using a chemometric approach and ROC analysis.

Results
The screening outcomes revealed that the pattern of methylguanidine, lactate, creatinine, threonine, aspartate, and trimethylamine (TMA), and TI, LD, CK, and serum creatinine were changed in CAD compared to NC. Statistical analysis demonstrated high precision (93.6% by NMR and 67.4% by clinical measures) to distinguish CAD from NC. Further analysis indicated that methylguanidine, arginine, and threonine, and TI, LD, and serum creatinine were significantly changed in CSA compared to MI. Statistical analysis demonstrated high accuracy (88.2% by NMR and 92.1% by clinical measures) to discriminate CSA from MI.

Conclusions
In contrast to other laboratory methods, 1H NMR–based metabolomics of filtered sera appears to be a robust, rapid, and minimally invasive approach to probe CSA and MI.
Identification of Friend or Foe: The Laboratory Challenge of Differentiating M-Proteins from Monoclonal Antibody Therapies
Authors: Mills John R , Murray David L 
Published: July 2018

AbstractBackgroundSince the first monoclonal antibody (mAb) therapy hit the market in 1996, the number of disorders treated with this class of therapeutics has seen tremendous growth, with over 50 antibody-based therapeutics currently approved for use in the US and Europe. This class of therapeutics recently made profound progress in the treatment of refractory multiple myeloma (MM). Treating MM with the mAbs will challenge the laboratory's ability to differentiate exogenous mAbs being used to treat patients from endogenous mAbs associated with disease.ContentAn overview of the therapeutic mAbs (t-mAbs) developed for the treatment of MM is provided. The anticipated impact of these therapies on patient care, laboratory testing, and clinical research is discussed. Efforts underway to develop strategies and technologies to help laboratories address the growing challenge of mAb interferences are reviewed.SummaryLaboratories can implement risk mitigation strategies at the preanalytical and postanalytical phase of testing to reduce the likelihood of reporting false-positive M-protein results in patients receiving t-mAbs. However, at the analytical phase of testing, current laboratory methods are ill-suited to differentiate between residual disease and residual drugs. Mass spectrometry–based methods might be best positioned to aid laboratories with the rapidly evolving landscape of MM treatment.
The Struggle Is Real: Lab Leaders Discuss Utilization Challenges During a 2-Day Summit
Authors: Brown Sarah , Dickerson Jane 
Published: July 2018

Abstract
Utilization management of laboratory testing is a trend increasing in relevance as the healthcare landscape continues to evolve toward value-based care, and many pediatric and adult laboratories are developing strategies for utilization management. The Pediatric Laboratory Guidance Service (PLUGS) started an annual conference dedicated to the important topics and challenges related to lab utilization. This year, the 2-day PLUGS Summit boasted over 10 hours of continuing medical education and several networking events to bring together leaders in the field of lab utilization. The theme of the 2016 meeting focused on bringing together clinical labs, reference labs, and insurance companies to increase the value of laboratory testing, in the context of the US health economy.