bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical Characterization of an Enzyme-Linked Immunosorbent Assay for the Measurement of Transforming Growth Factor β1 in Human Plasma
Authors: Giles Brendan M , Underwood Timothy T , Benhadji Karim A , Nelson Diana K S , Grobeck Lisa M , Lin Boris , Wang Shuaicheng , Fill Jeffrey A , Man Michael , Pitts Kelly R , Bamberg Alison 
Published: August 2018

AbstractBackgroundThe transforming growth factor β (TGF-β)–signaling pathway has emerged as a promising therapeutic target for many disease states including hepatocellular carcinoma (HCC). Because of the pleiotropic effects of this pathway, patient selection and monitoring may be important. TGF-β1 is the most prevalent isoform, and an assay to measure plasma levels of TGF-β1 would provide a rational biomarker to assist with patient selection. Therefore, the objective of this study was to analytically validate a colorimetric ELISA for the quantification of TGF-β1 in human plasma.MethodsA colorimetric sandwich ELISA for TGF-β1 was analytically validated per Clinical and Laboratory Standards Institute protocols by assessment of precision, linearity, interfering substances, and stability. A reference range for plasma TGF-β1 was established for apparently healthy individuals and potential applicability was demonstrated in HCC patients.ResultsPrecision was assessed for samples ranging from 633 to 10822 pg/mL, with total variance ranging from 28.4% to 7.2%. The assay was linear across the entire measuring range, and no interference of common blood components or similar molecules was observed. For apparently healthy individuals, the average TGF-β1 level was 1985 ± 1488 pg/mL compared to 4243 ± 2003 pg/mL for HCC patients. Additionally, the TGF-β1 level in plasma samples was demonstrated to be stable across all conditions tested, including multiple freeze–thaw cycles.ConclusionsThe ELISA described in this report is suitable for the quantification of TGF-β1 in human plasma and for investigational use in an approved clinical study.
Red Blood Cell Transfusions and Anemia on Admission Are Associated with Poor Outcomes in Necrotizing Soft Tissue Infections
Authors: Lieberman Joshua A , Stansbury Lynn G , Kufera Joseph A , Chiu William C , Punch Laurie J , Hess John R , Scalea Thomas M , Henry Sharon M 
Published: August 2018

Abstract

Background
Necrotizing soft tissue infections (NSTIs) are highly morbid infections often requiring critical care and transfusion support. We explored a large 2-year experience from a regional trauma center with a dedicated soft tissue service (STS) in an attempt to identify factors in current care with potential for improving outcomes for these critically ill patients.

Methods
New adult (&gt;17 years) STS admissions, 2008–2009, were identified from the Trauma Registry. Patient records were extracted and assessed via descriptive statistics, univariate analysis, and multivariable logistic regression models.

Results
Mortality among 253 eligible primary admissions was 8.3% overall and 10.3% for those with an admission diagnosis of NSTI. No significant differences in wound characteristics, use of VAC (vacuum-assisted closure) dressing or hyperbaric oxygen, or wound microbiology emerged between survivors and nonsurvivors. Median time to first debridement was 5 h (interquartile range, 2–21 h). Multivariable modeling indicated association of worse outcome (death or discharge to chronic/rehab care) with age &gt;60 years [odds ratio (OR), 3.82; P &lt; 0.001], anemia (OR, 0.98; P = 0.03), increasing number of transfusions (OR, 1.09; P &lt; 0.001), NSTI diagnosis (OR, 2.47; P = 0.005), preexisting diabetes mellitus (OR, 3.20; P = 0.001), and low admission hemoglobin (OR, 0.80; P = 0.004).

Conclusions
Mortality was less than previously reported. Number of transfusions and anemia at admission emerged as risk factors for poor outcomes. Future research should focus on the effects of transfusion on NSTI outcomes, on potentially confounding factors, and on whether a restrictive transfusion strategy reduces mortality.
Study Design Considerations for Cancer Biomarker Discoveries
Authors: Zheng Yingye 
Published: August 2018

Abstract

Background
Biomarker discovery studies have generated an array of omic data; however, few novel biomarkers have reached clinical use. Guidelines for rigorous study designs are needed.

Content
Biases frequently occur during sample selection, outcome ascertainment, or unblinded sample handling and the assaying process. The principles of a prospective specimen collection and retrospective blinded evaluation design can be adapted to mitigate various sources of biases in discovery. We recommend establishing quality biospecimen repositories using matched 2-phase designs to minimize biases and maximize efficiency. We also highlight the importance of taking the clinical context into consideration in both sample selection and power calculation for discovery studies.

Summary
Biomarker discovery research should follow rigorous design principles in sample selection to avoid biases. Consideration of clinical application and the corresponding biomarker performance characteristics in study designs will lead to a more fruitful discovery study.
Algorithms Used in Ovarian Cancer Detection: A Minireview on Current and Future Applications
Authors: Gupta Vishaal , Bernardini Marcus Q 
Published: August 2018

Abstract

Background
Ovarian cancer is the 5th most common cause of cancer death among women in the US. Currently, there is no screening algorithm for asymptomatic women that has been shown to lower mortality rates. Screening is currently not recommended and has been shown to increase harm. Epithelial ovarian cancer (EOC) detection is reviewed, with a focus on high-grade serous, clear-cell, and endometrioid histotypes.

Content
A review of current literature surrounding tools used in detection of ovarian cancer will be presented. CA 125, HE4, risk of ovarian cancer algorithm (ROCA), risk of malignancy algorithm (ROMA), risk of malignancy (RMI), OVA1, and future potential biomarkers are reviewed.

Summary
Screening and early identification of EOC is currently managed as a single disease entity. However, recent evidence has shown ovarian cancer varies with relation to cellular origin, pathogenesis, molecular alterations, and prognosis, depending on histotype. There is a clear need for future studies identifying histotype-specific preclinical tumor markers to aid in detection and improvement of survival rates.
Longitudinal Analysis of Erythrocyte and Plasma Protoporphyrin Levels in Patients with Protoporphyria
Authors: Gou Eric , Weng Cindy , Greene Tom , Anderson Karl E , Phillips John D 
Published: August 2018

Abstract

Background
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited cutaneous porphyrias resulting from decreased activity of ferrochelatase and gain-of-function mutations of δ-aminolevulinic acid synthase-2, respectively. Both of these protoporphyrias cause increased protoporphyrin levels that cause photosensitivity and may lead to hepatopathy and further increases in erythrocyte and plasma porphyrin levels.

Methods
We evaluated erythrocyte protoporphyrin and plasma porphyrin levels in all subjects with EPP (83 subjects) or XLP (9 subjects) without evidence of liver disease tested repeatedly at a single laboratory over 25 years.

Results
Intersubject variation contributed more than intrasubject variation (78.86% vs 21.14%) to overall variability, and longitudinal variability, estimated by CV, averaged 26%. Erythrocyte total protoporphyrin levels were similar in males and females with EPP (ratio, 0.99; 95% CI, 0.82–1.21; P = 0.96) but were higher in males than females with XLP, although this difference was not statistically significant (ratio, 0.76; 95% CI, 0.43–1.36; P = 0.35). Analysis of 20 subjects from 9 separate families showed significant effects of family compared with effects of individual variation on total variance (50% vs 25%; P &lt; 0.0001).

Conclusion
Variation of erythrocyte total protoporphyrin up to 25% is expected in patients with protoporphyria, whereas greater increases might raise concern for protoporphyric hepatopathy.
Analytical Validation of qPCR-Based Multivariate Index Assays in a Clinical Laboratory: Practical Challenges and Limitations
Authors: Sesler Cheryl L , Grigorenko Elena V 
Published: August 2018

Abstract

Background
Multivariate index assays (MIAs) to evaluate disease status and/or therapeutic efficacy are increasingly being used in clinical laboratories as laboratory-developed tests (LDTs). Before clinical use, diagnostic and analytical performance specifications of LDTs must be established. Several regulatory guidelines have been published that address specific components of validation procedures, but the interpretation for the analytical validation of MIAs is ambiguous and creates confusion when implementing a novel MIA in the clinical laboratory.

Content
CLSI guidelines and published methods were evaluated to develop a validation strategy to establish analytical sensitivity, precision, specificity, and stability for qPCR-based MIAs. Limitations and challenges identified while evaluating guidelines and literature and implementing this strategy are discussed in this review, including sample sourcing and integrity, laboratory contamination, and sample throughput. Due to the diversity of qPCR-based MIAs, we discuss additional considerations for researchers intending to transfer MIAs to a clinical laboratory.

Summary
A practical strategy to assess the analytical performance characteristics for validation of qPCR-based MIAs was developed and tested before diagnostic clinical use. Several important limitations, challenges, and considerations were identified during development of the analytical validation procedures that are not addressed in regulatory guidelines or published literature. The described strategy can provide insight for future developers of MIAs and clinical laboratories implementing MIAs as LDTs.
Reengineering Critical Laboratory Testing for Timely Chemotherapeutic Management
Authors: Yi Xin , Leung Edward Ki Yun , Mika Diane , Wolsky Rebecca J , Van Slambrouck Charles , Leanse Julie , Nabhan Chadi , Yeo Kiang-Teck J 
Published: August 2018

Abstract

Background
Delivery of cytotoxic therapy is a complex multifaceted process that involves harmonized collaboration between all systems involved. Optimizing laboratory turnaround time (TAT) ensures timely delivery of chemotherapy, which potentially translates into improved patient outcomes and satisfaction. In this study, we aimed to reduce the laboratory TAT for key laboratory tests to optimize the timely administration of chemotherapy.

Methods
TAT data for complete blood count (CBC) and comprehensive metabolic panel (CMP) included specimen collection to receipt (Col-Rcv), specimen receipt to result release (Rcv-Res), and the overall TAT from specimen collection to result release (Col-Res). Work flows were reconfigured to transport CBC specimens directly to the hematology laboratory after collection and to treat all CMP samples from chemotherapy clinics as urgent [i.e., shortest turnaround time (STAT)]. From the CMP, total bilirubin and creatinine—the 2 key analytes for liver and renal toxicity assessment before chemotherapy drug administration—were analyzed on ABL 800 whole blood analyzers to further improve the laboratory TAT.

Results
CBC showed a significant reduction in the median (Col-Res) TAT to 16 min (P &lt; 0.0001). For CMP, by processing all specimens as STAT samples, the median (Col-Res) TAT was reduced from 74 min to 54 min (P &lt; 0.0001), and it was further reduced to 9 min (P &lt; 0.0001) for total bilirubin and creatinine.

Conclusion
Careful work flow analysis and reengineering of preanalytical and analytical process for key laboratory tests significantly reduced median overall TAT to &lt;20 min, which helped facilitate more timely delivery of chemotherapy, without necessitating the construction of a satellite laboratory.
Laboratory Performance on Reporting Monoclonal Gammopathy During Cerebrospinal Fluid Oligoclonal Banding Analysis from External Quality Assessment Surveys
Authors: Chen Yu 
Published: August 2018

Abstract

Objective
Cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis is a sensitive test used to mainly aid multiple sclerosis (MS) diagnosis. Monoclonal gammopathy is usually an incidental finding during CSF OCB analysis. The aim of this study was to assess laboratory performance on reporting monoclonal gammopathy pattern during CSF OCB analysis based on external quality assessment surveys.

Methods
The CSF OCB surveys from the College of American Pathologists (CAP) from 2010 to 2015 were reviewed. The UK National External Quality Assessment Service (NEQAS) CSF OCB surveys from 2014 to 2017 were also reviewed. All monoclonal gammopathy patterns were confirmed by serum protein electrophoresis followed by immunofixation on a Sebia Hydrasys analyzer.

Results
There were 11 monoclonal gammopathy cases identified in the CAP OCB survey from 2010 to 2015. The average rate of CAP participants that correctly reported the pattern was 25.1% (range, 2.4%–66.7%). The most common pattern incorrectly reported was the systemic inflammation pattern, followed by the oligoclonal bands present/positive pattern. The NEQAS OCB survey from 2014 to 2017 had 4 monoclonal gammopathy cases and indicated a much higher number (average, 88.5%; range, 84.1%–90.8%) of participating laboratories to successfully detect monoclonal gammopathy.

Conclusion
Monoclonal gammopathy is still an underrecognized pattern in the CSF OCB analysis by the CAP participating laboratories and warrants further education.
Rapid Somatic Mutation Testing in Colorectal Cancer by Use of a Fully Automated System and Single-Use Cartridge: A Comparison with Next-Generation Sequencing
Authors: Al-Turkmani M Rabie , Godwin Kelley N , Peterson Jason D , Tsongalis Gregory J 
Published: August 2018

Abstract

Background
Molecular tests have been increasingly used in the management of various cancers as more targeted therapies are becoming available as treatment options. The Idylla™ system is a fully integrated, cartridge-based platform that provides automated sample processing (deparaffinization, tissue digestion, and DNA extraction) and real-time PCR-based mutation detection with all reagents included in a single-use cartridge. This retrospective study aimed at evaluating both the Idylla KRAS and NRAS-BRAF-EGFR492 Mutation Assay cartridges (research use only) against next-generation sequencing (NGS) by using colorectal cancer (CRC) tissue samples.

Methods
Forty-four archived formalin-fixed paraffin-embedded (FFPE) CRC tissue samples previously analyzed by targeted NGS were tested on the Idylla system. Among these samples, 17 had a mutation in KRAS proto-oncogene, GTPase (KRAS), 5 in NRAS proto-oncogene, GTPase (NRAS), and 12 in B-Raf proto-oncogene, serine/threonine kinase (BRAF) as determined using the Ion AmpliSeq 50-gene Cancer Hotspot Panel v2. The remaining 10 samples were wild-type for KRAS, NRAS, and BRAF. Two 10-μm FFPE tissue sections were used for each Idylla run, 1 for the KRAS cartridge, and 1 for the NRAS-BRAF-EGFR492 cartridge. All cases met the Idylla minimum tumor content requirement for KRAS, NRAS, and BRAF (≥10%). Assay reproducibility was evaluated by testing commercial controls derived from human cell lines, which had an allelic frequency of 50% and were run in triplicate.

Results
The Idylla system successfully detected all mutations previously identified by NGS in KRAS (G12C, G12D, G12V, G13D, Q61K, Q61R, A146T), NRAS (G12V, G13R, Q61H), and BRAF (V600E). Compared with NGS, Idylla had a sensitivity of 100%. Analysis of the mutated commercial controls demonstrated agreement with the expected result for all samples and 100% reproducibility. The Idylla system produced results quickly with a turnaround time of approximately 2 h.

Conclusion
The Idylla system offers reliable and sensitive testing of clinically actionable mutations in KRAS, NRAS, and BRAF directly from FFPE tissue sections.
Circulating Tumor DNA for Early Cancer Detection
Authors: Fiala Clare , Kulasingam Vathany , Diamandis Eleftherios P 
Published: August 2018

Abstract

Background
Cancer cells release circulating tumor DNA (ctDNA) into the bloodstream, which can now be quantified and examined using novel high-throughput sequencing technologies. This has led to the emergence of the “liquid biopsy,” which proposes to analyze this genetic material and extract information on a patient's cancer using a simple blood draw.

Content
ctDNA has been detected in many advanced cancers. It has also been proven to be a highly sensitive indicator of relapse and prognosis. Sequencing the genetic material has also led to the discovery of mutations targetable by existing therapies. Although ctDNA screening is more expensive, it is showing promise against circulating tumor cells and traditional cancer biomarkers. ctDNA has also been detected in other bodily fluids, including cerebrospinal fluid, urine, saliva, and stool.
The utility of ctDNA for early cancer detection is being studied. However, a blood test for cancer faces heavy obstacles, such as extremely low ctDNA concentrations in early-stage disease and benign mutations caused by clonal hematopoiesis, causing both sensitivity and specificity concerns. Nonetheless, companies and academic laboratories are highly active in developing such a test.

Conclusion
Currently, ctDNA is unlikely to perform at the high level of sensitivity and specificity required for early diagnosis and population screening. However, ctDNA in blood and other fluids has important clinical applications for cancer monitoring, prognosis, and selection of therapy that require further investigation.
The Iraqi Communist Party 1934–79
Authors: Sluglett Peter 
Published: August 2018

Abstract
A survey of the history of the Iraqi Communist Party (ICP), from it formation to the rise of Saddam Hussein, is presented. The heydays of the party were in the two decades following the end of World War II when communist activities played a central role in the political, economic and cultural transformations of Iraq. The ICP’s influence has declined sharply in recent times and today it appears on the verge ceasing to exist as an effective political force.
The Communist Party’s activities among the peasantry
Authors: Sbahi Aziz 
Published: August 2018

Abstract
Although the activities of the Iraqi Communist Party (ICP) were primarily centred in the major cities, the party did not neglect the countryside. During the 1940s and 1950s, the ICP’s cadres played a central role in forming peasant associations in several regions of the country particularly in Kurdistan and the Middle Euphrates. Communist-led peasant movements tended to focus on legal rights and economic demands, scoring some impressive gains for Iraq’s most destitute classes. These activities also helped spread general notions of social and political justice, democracy, citizenship, class-consciousness and socialism. This form of activist education would play a significant role in the success of the anti-Monarchic revolution of 1958 and the subsequent agrarian reform programmes.
The 1948 Wathba revisited: Comrade Fahd and the mass appeal of Iraqi communism
Authors: Thompson Elizabeth F. 
Published: August 2018

Abstract
The 1948 Wathba protests in Iraq crystallized the communist party’s success in mobilizing ordinary citizens around democratic ideals, against the neo-feudal politics of the British-controlled monarchy. This mobilization bore fruit in the 1958 revolution, but is often overlooked by historians who focus on the failure of a communist revolution. The inclusive, cross-sectarian democratic movement is remembered, but not revived in post-Ba`thist Iraq today.
From regional politics to street demonstrations: Changes in the Iraqi Communist Party’s political strategies in the post-war era
Authors: Yamao Dai 
Published: August 2018

Abstract
This article analyses how the Iraqi Communist Party (ICP) altered its political strategies in post-war Iraq. After the decline of the political presence, the ICP formed large alliances with small parties in the third round of local and national elections, opting to support candidates on a national scale; in doing so, the ICP achieved significant breakthrough. The party’s election strategy not only led to the ICP’s success but also to the overall stabilization of Iraqi party politics. After the rise of ISIS, the ICP overcame its ideological differences with Sadrist factions that similarly stood alongside the masses; pursuing large-scale demonstrations, the ICP found further opportunities to carry out its political activities. The ICP has thus been adroit in adapting its political strategies according to political and social circumstances. As Islamist groups have seized political power and religious sentiment has spread, the ICP might be seen as pursuing the best of strategies that remain available to it.
Theatres of blood: Performative violence in Iraq
Authors: Tripp Charles 
Published: August 2018

Abstract
This article examines much of the violence of the past two decades in Iraq through the prism of performative politics. This draws attention to its spectacular nature, its repertoires and aesthetics, where blood becomes the common referent in a theatre of state power and resistance. Beyond the spectacle, however, violence is performative in that it possesses causal power. Violence has shaped the ways in which conflicts have been understood and organized, reproducing and reinforcing particular identities, institutions and attitudes in Iraq. Performative violence became a spectacle of horror and, through that horror a technology for the demarcation of whole categories of Iraqi citizen whose blood Islamic State and others licensed themselves to shed. Both nascent state forces and those resisting them, as well the foreign powers active in the Iraqi theatre, had every interest in making manifest their competence and their potential in the use of violence. Regardless of the identity of the parties involved, or the ends they were pursuing, violence has thus become a key technology of power. To perform it has been to assert the right to power in the political landscape of Iraq.
Diaries of Iraqi soldiers: Views from inside Saddam’s army
Authors: Sassoon Joseph , Walter Alissa 
Published: August 2018

Abstract
This article presents rarely seen glimpses into life in the barracks of the Iraqi Army during the Gulf War (1990–91). We analyse fifteen diaries of Iraqi soldiers found in the Kuwait Dataset of the Iraqi Ba’th Party Archives, which was first opened to researchers in July 2015. These diaries shed new light on the mind-sets, ideological frameworks, morale and daily lives of Iraqi rank-and-file soldiers. We ask the following questions: did Iraqi soldiers support the invasion and occupation of Kuwait and accept Saddam Hussein’s rationales for the war? How did Iraqi soldiers view the United States and its coalition partners? These diaries also provide clues about why so many retreating soldiers rose up against Saddam in country-wide protests one week after Iraq’s defeat in the war. Although diaries from the US Civil War and the First and Second World Wars have been thoroughly examined by historians and literary scholars, few diaries of soldiers from the modern Arab world have been studied. This article fills an important gap in knowledge about the experiences of soldiers in modern authoritarian regimes and about the Gulf War.