bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of reversible pulmonary arterial hypertension associated with incontinentia pigmenti
Authors: Atallah Veronique , Meot Mathilde , Kossorotoff Manoelle , Galmiche‐Rolland Louise , Lardeux Claude , Neven Benedicte , Bodemer Christine , Bonnet Damien 
Published: July 2018

Incontinentia pigmenti (IP) is a multisystemic disorder in which pulmonary arterial hypertension (PAH) is a severe and rarely reported association. The prognosis has been poor in reported cases. In our patient, IP was diagnosed during the neonatal period with a combination of cutaneous, ophthalmic, and neurological symptoms. The infant experienced severe collapse with bradycardia during general anesthesia to treat retinal telangiectasia. Echocardiography after resuscitation revealed suprasystemic pulmonary hypertension (PH). Right heart catheterization (RHC) confirmed precapillary PAH not responding to acute vasodilatation test. Lung biopsy was performed to exclude alveolo‐capillary dysplasia. Upfront triple therapy with endothelin receptor antagonist, PDE5 inhibitors, and prostacyclin was started. Due to a potential inflammatory mechanism of this acute PAH in the setting of IP, TNF‐alpha blockers and steroids were associated. The evolution was favorable with progressive normalization of the pulmonary artery pressure confirmed by RHC after six months. Doses of PAH drugs were tapered down, and finally all PAH treatments could be stopped after 18 months. Subsequent controls including physical exams and echocardiograms did not show signs of PH. This unusual reversible case of pediatric PAH without associated congenital heart disease or portal hypertension highlights the potential reversibility of pediatric PH when an inflammatory mechanism can be suspected. This is the first reported case of non‐fatal isolated PAH associated with IP.
Combined use of polypill components in patients with type 2 diabetes mellitus
Authors: Janssen Vivi E , Visseren Frank L , de Boer Anthonius , Grobbee Diederick E , Westerink Jan , van der Graaf Yolanda , Lafeber Melvin 
Published: July 2018

ObjectivesA polypill containing aspirin, a statin and blood pressure (BP)-lowering agents has been proposed for the prevention of cardiovascular disease. To increase adherence and reduce the gaps between indicated and used therapy, a polypill might be of interest for patients with type 2 diabetes (T2DM). Our aim was to assess the prevalence of the combined use of polypill components in patients with T2DM over time.MethodsThe combined use of polypill components was assessed between 1996 and 2015 in patients with T2DM in the prospective SMART cohort ( n = 1828). The results were dichotomized into patients without ( n = 568) and with ( n = 1260) vascular disease. The patient characteristics associated with the use of polypill components were evaluated.ResultsIn total, 19% of patients with T2DM without vascular disease received a statin and ≥2 BP-lowering agents (‘cardiovascular polypill’) and 13% received additional oral glucose-lowering therapy (‘diabetic polypill’). Of the patients with T2DM with vascular disease, 42% received the combination of an antiplatelet agent, a statin and ≥2 BP-lowering agents (‘cardiovascular polypill’) and 30% received additional glucose-lowering therapy (‘diabetic polypill’). The prevalence of the use of the cardiovascular and diabetic polypill combination has substantially increased between 1996 and 2015 to 36 and 32% in patients without vascular disease and to 67 and 57% in patients with vascular disease.ConclusionsPatients with T2DM frequently use polypill components, often together with oral glucose-lowering agents, and this rate of use has increased steadily between 1996 and 2015. Introducing a cardiovascular or diabetic polypill for patients with T2DM seems to be highly relevant.
BCL-2 inhibition in AML: an unexpected bonus?
Authors: Konopleva Marina , Letai Anthony 
Published: July 2018

AbstractB-cell lymphoma 2 (BCL-2) was discovered at the breakpoint of the t(14;18) in follicular lymphoma >30 years ago. Although inhibition of BCL-2 first proved valuable in lymphoid malignancies, clinical progress in myeloid malignancies lagged. Here, we summarize the basic biology and preclinical results that spurred clinical BCL-2 inhibition in acute myeloid leukemia (AML). Response rates and toxicity for venetoclax in combination with standard AML agents, such as azacitidine, decitabine, and low-dose cytarabine, compare favorably with conventional induction chemotherapy. Durability of response requires further study.
The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort
Authors: Stahl Maximilian , DeVeaux Michelle , de Witte Theo , Neukirchen Judith , Sekeres Mikkael A. , Brunner Andrew M. , Roboz Gail J. , Steensma David P. , Bhatt Vijaya R. , Platzbecker Uwe , Cluzeau Thomas , Prata Pedro H. , Itzykson Raphaël , Fenaux Pierre , Fathi Amir T. , Smith Alexandra , Germing Ulrich , Ritchie Ellen K. , Verma Vivek , Nazha Aziz , Maciejewski Jaroslaw P. , Podoltsev Nikolai A. , Prebet Thomas , Santini Valeria , Gore Steven D. , Komrokji Rami S. , Zeidan Amer M. 
Published: July 2018

Key Points
IST leads to a response in nearly half, and to RBC transfusion independence in about a third, of selected lower-risk MDS patients. Hypocellularity of bone marrow and the use of horse ATG plus cyclosporine are associated with increased rates of transfusion independence.
Integration of Germline Pharmacogenetics Into a Tumor Sequencing Program
Authors: Hertz Daniel L. , Glatz Andrew , Pasternak Amy L. , Lonigro Robert J. , Vats Pankaj , Wu Yi-Mi , Anderson Bailey , Rabban Erica , Mora Erika , Frank Kevin , Robinson Dan R. , Mody Rajen J. , Chinnaiyan Arul 
Published: July 2018

Purpose Evidence-based guidelines inform treatment decisions for patients for whom germline genetic information is available. Our real-time tumor sequencing program, which makes precision treatment decisions for patients with cancer, produces matched germline information, providing a unique opportunity to efficiently implement pharmacogenetics and benefit patients. Methods The germline genetic database from the Michigan Oncology Sequencing (MI-Oncoseq) program was searched for 21 clinically actionable polymorphisms in five cancer-relevant genes: TPMT, DPYD, CYP2C19, CYP3A5, and UGT1A1. Residual germline DNA was sent to an external Clinical Laboratory Improvement Amendments–approved laboratory for confirmatory genotyping. The medical records of MI-Oncoseq patients with actionable phenotypes were searched for receipt of relevant drugs and to determine whether having genetic information at the time of treatment would have led to a treatment recommendation. Results All nine variants in TPMT, DPYD, and CYP2C19 that were detected in MI-Oncoseq were confirmed by external genotyping. Genotype determinations could not be made for CYP3A5*3, UGT1A1*28, or UGT1A1*80. On the basis of retrospective assessment of 115 adult and pediatric patient records, 4.3% (n = 5) had a potentially clinically actionable phenotype for TPMT, DPYD, or CYP2C19 and received a relevant medication. After accounting for differences in adult and pediatric recommendations, three of these patients could have received a treatment recommendation at the time of prescribing. Conclusion Germline genotype determinations for TPMT, DPYD, and CYP2C19 can be used to make evidence-based treatment recommendations in MI-Oncoseq patients. Although the proportion of patients for whom recommendations can be made is small, this added value to MI-Oncoseq and patient care comes at no additional genotyping cost. Pharmacogenetic assessment should be integrated into tumor sequencing programs that genotype matched germline DNA; however, the complexity and additional cost of implementing pharmacogenetics remain challenging.
Plasticity of differentiated cells in wound repair and tumorigenesis, part I: stomach and pancreas
Authors: Burclaff Joseph , Mills Jason C. 
Published: July 2018

ABSTRACT
For the last century or so, the mature, differentiated cells throughout the body have been regarded as largely inert with respect to their regenerative potential, yet recent research shows that they can become progenitor-like and re-enter the cell cycle. Indeed, we recently proposed that mature cells can become regenerative via a conserved set of molecular mechanisms (‘paligenosis’), suggesting that a program for regeneration exists alongside programs for death (apoptosis) and division (mitosis). In two Reviews describing how emerging concepts of cellular plasticity are changing how the field views regeneration and tumorigenesis, we present the commonalities in the molecular and cellular features of plasticity at homeostasis and in response to injury in multiple organs. Here, in part 1, we discuss these advances in the stomach and pancreas. Understanding the extent of cell plasticity and uncovering its underlying mechanisms may help us refine important theories about the origin and progression of cancer, such as the cancer stem cell model, as well as the multi-hit model of tumorigenesis. Ultimately, we hope that the new concepts and perspectives on inherent cellular programs for regeneration and plasticity may open novel avenues for treating or preventing cancers.
A distância entre a cidade efêmera e a memória das pedras: arquitetura e hierarquia no Rio de Janeiro do período joanino
Authors: Pinto Carlos Eduardo Pinto de 
Published: July 2018

Resumo: O artigo aborda o uso da arquitetura efêmera como forma de consolidação da sociedade de Corte no Rio de Janeiro durante o Período Joanino. Por meio de reflexões a respeito das origens barrocas desse recurso, se defende a existência de uma relação hierárquica entre a cidade ideal, manifestada nos aparatos efêmeros, e a cidade material. Esta, a cidade sombria, das indefinições físicas e sociais, dos ruídos, do mau-cheiro; aquela, a cidade iluminada, da ordenação simétrica e hierarquizada dos espaços e dos corpos, da música, do perfume. A comparação entre as duas, em busca de seus limites e interseções, determina a rota seguida pelo texto.Abstract: The article discusses the use of ephemeral architecture as means of consolidating the Court Society in Rio de Janeiro during the reign of Dom João. Regarding these manifestations in their dialogue with the Baroque, we defend the existence of a hierarchical relationship between the ideal city, manifested in ephemeral apparatuses, and the material one. This, the dark city, of the physical and social inaccuracies, of the noises and bad smell; that, the illuminated city, of the symmetrical and hierarchical ordering of spaces and bodies, of music and perfume. The comparison between both, regarding their limits and intersections, determines the route followed by the text.
A Study of Correlations between Perceived Supervisor Support, Organizational Identification, Organizational Citizenship Behavior, and Burnout at Schools
Authors: Uzun Tevfik 
Published: July 2018

<p style="text-align:justify">In this research, it is aimed to study the correlations between perceived supervisor supports (PSS), organizational identification (OI), organizational citizenship behavior (OCB), and burnout of teachers. The research was conducted from the perspective of social change and identity theories. The study group of the research consists of 234 teachers working in the public high schools in Giresun city center during the 2016. In order to collect data in the research, Perceived Supervisor Support Scale developed by Kottke & Sharafinski, Organizational Identification Scale developed by Mael & Ashforth, Organizational Citizenship Behaviors Scale developed by DiPaola, Tarter & Hoy, and "Burnout Scale" developed by Pines were used. The correlations between variables are tested with the structural equation model. According to the results, PSS positively affects the OI and OCB and negatively affects the burnout. OI positively affects the organizational citizenship behavior and negatively affects the burnout. OI plays a partial mediation role in the correlation between PSS of teachers and their OCB and burnout level. The results contribute to the integration of social change and social identity theories in description of organizational behavior.</p>
Accuracy of a Direct Progesterone Immunoassay
Authors: Shankara-Narayana Nandini , Zawada Shannon , Walters Kirsty A , Desai Reena , Marren Anthony , Handelsman David J 
Published: July 2018

Abstract

Background
Beyond the established role of serum progesterone measurement in the luteal phase of menstrual cycle to confirm recent ovulation, it is also increasingly used to detect premature luteinization during in vitro fertilization (IVF) hyperstimulation, where late follicular phase increase in serum progesterone is reportedly associated with adverse pregnancy outcomes. Virtually all serum progesterone measurements in clinical and IVF practice use direct, nonextraction immunoassays, often in multiplex, high-throughput platform assays optimized for high, postovulatory, midluteal phase serum progesterone concentrations. However, the performance of direct progesterone immunoassays for smaller increases is not established.

Methods
We studied 254 women undergoing IVF hyperstimulation with serum progesterone around the time of human chorionic gonadotropin (hCG) administration, measured in each sample by a direct progesterone immunoassay (Beckman Coulter Access) and by LC-MS.

Results
Immunoassay overestimated serum progesterone in almost every sample with an increasingly high variability and deviation at lower concentrations (immunoassay &lt;5 nmol/L, equivalent to LC-MS &lt;2 nmol/L).

Conclusions
Immunoassay consistently overestimates serum progesterone levels so that low measurements (immunoassay &lt;5 nmol/L) are too inaccurate to be used quantitatively. The utility of higher serum progesterone measurements by immunoassay and serum progesterone and other steroids measured by multiplex LC-MS profiling in predicting IVF pregnancy outcomes warrants further investigation. There is a need for caution in clinical diagnosis of premature luteinization based on increased late follicular phase serum progesterone measurements using direct progesterone immunoassay that consistently overestimates low serum progesterone concentrations.
A Novel System Control for Quality Control of Diagnostic Tests Based on Next-Generation Sequencing
Authors: Chan Maurice , Smirnov Arseny , Mulawadi Fabianus , Lim Priscilla , Lim Wen-Huey , Leong See Ting , Low Hwee Meng , Yee Mei Qi , Yeo Yong Qiang , Zhou Xin , Lee Charlie , Huang Wen , Welebob Louis , Wu Mengchu 
Published: July 2018

Abstract

Background
We describe a novel system control (SC) implemented in an automated AmpliSeq™-based next-generation sequencing (NGS)2 run that simultaneously acts as (a) an external positive/sensitivity control, (b) a spike-in QC for DNA extraction, and (c) a nontemplate control to detect exogenous DNA contamination.

Methods
Plasmids carrying wild-type tobacco mosaic virus sequence and a sequence with three designed mutations were synthesized and mixed, such that the mutations are present at 5% variant frequency in the mixture designated as SC. SC was used as a stand-alone sample and spiked into each sample in each run. A cell line–derived reference material, in both a formalin-fixed paraffin-embedded (FFPE) sample and genomic DNA (gDNA), was sequenced in the same runs.

Results
By interpolation, 100 fg SC spiked in FFPE sample produced sequencing coverage equivalent to approximately 3 fg in the gDNA. In the SC-only sample, all three designed mutations were recovered around 5% as expected, while no significant reads of human genome were present. In samples with a common PCR inhibitor, coverage for both SC and target amplicons were eliminated. An inverse relationship between the coverage of SC and DNA input was observed. In clinical samples, the ratio of SC to the median coverage of sample can be used to indicate insufficient DNA input.

Conclusions
The SC is an elegant and comprehensive QC concept for NGS-based diagnostic tests.
A Quantitative Method for the Measurement of Dried Blood Spot Amino Acids Using Ultra-Performance Liquid Chromatography
Authors: Bloom Kaitlyn , Ditewig Meyers Gail , Bennett Michael J 
Published: July 2018

Abstract

Background
Measurement of amino acids in dried blood spots has been extensively used for the detection of newborns with various inborn errors of amino acid metabolism including phenylketonuria (PKU) and maple syrup urine disease (MSUD). Whereas blood spot amino acid measurement has been invaluable for initial diagnosis, the relative insensitivity of blood spot measurement has found limited use in lifelong monitoring of patients with these disorders. The work described here outlines the evaluation of blood spot amino acid analysis using ultra-performance liquid chromatography (UPLC©) for use in follow-up testing.

Methods
Dried blood spot amino acids were derivatized with a proprietary AccQTag® reagent and separated using UPLC. Plasma amino acids from dried bloods spots were obtained from 318 patient samples and compared to corresponding plasma samples measured using the same UPLC method.

Results
Dried blood spot amino acid concentrations were highly correlated but negatively biased vs plasma concentrations. Interassay imprecision studies using UPLC demonstrated a %CV for phenylalanine of 4.81%–16.07%, tyrosine 5.62%–20.16%, valine 4.23%–15.46%, leucine 8.3%–15.3%, and isoleucine 4.25%–16.80%. Intraassay imprecision studies using UPLC demonstrated a %CV for phenylalanine of 0.42%–3.4%, tyrosine 1.6%–7.85%, valine 0.14%–1.84%, leucine 0.28%–2.01%, and isoleucine 0.6%–2.65%. Blood spot amino acid concentrations were stable for at least 3 days at temperatures up to 65 °C.

Conclusions
This UPLC-based method can reliably measure clinically significant amino acids in dried blood spots.
Analytical and Clinical Evaluation of the NOWDiagnostics ADEXUSDx Human Chorionic Gonadotropin Test Using Whole Blood
Authors: Nerenz Robert D , Bell Jennifer R , Montes de Oca Nancy , Short Joann , Mims Theresa , Cleeton Patrick A , Daniel Moore J , Humphries Roger L 
Published: July 2018

Abstract

Background
Point-of-care (POC) urine qualitative human chorionic gonadotropin (hCG) devices are used to rapidly assess pregnancy status, but many of these devices are susceptible to false-negative results caused by increased concentrations of hCG β core fragment (hCGβcf) that does not contain hCGβcf.

Methods
Purified hCG was added to hCG-negative heparinized whole blood to generate samples with known hCG concentrations, and the resulting samples were used to evaluate device sensitivity, low-end reproducibility, high-dose hook effect, intermediate range performance, acceptable sample volume, acceptable hematocrit range, and lot-to-lot variation. Device performance was also prospectively evaluated in 40 pregnant and 40 nonpregnant women aged 18–44 years in a hospital-based clinic or an academic hospital emergency department.

Results
All device observations were positive using a whole blood sample containing a plasma hCG concentration of 2.2 × 106 IU/L, and all device observations were positive from18 IU/L to 1.2 × 103 IU/L and from 2.5 × 104 IU/L to 2.2 × 106 IU/L. Three invalid results were observed in the intermediate range because of decreased control line intensity. The minimum sample volume was 30 μL, and maximum hematocrit was 46%. In 40 pregnant and 40 nonpregnant women aged 18–44 years, the device generated 100% concordance with urine qualitative and plasma quantitative test results.

Conclusions
The ADEXUSDx™ hCG test demonstrates acceptable performance for the determination of pregnancy status using capillary fingerstick samples.
α-Glutathione S-Transferase: A New Biomarker for Liver Injury?
Authors: Maina Ian , Rule Jody A , Wians Frank H , Poirier Michael , Grant Lafaine , Lee William M 
Published: July 2018

Abstract

Background
Serum alanine and aspartate aminotransferases (ALT/AST) have been the gold standard for detection and quantification of liver injury for over 6 decades, but have relatively long half-lives (T½) (literature estimates approximately 17 and 47 h, respectively) and thus do not reflect immediate changes in liver injury or recovery. A new point-of-care immunoassay for α-glutathione S-transferase (α-GST) measures this cytosolic liver enzyme with a predicted T½ of 60–90 min based on preliminary studies and might enable earlier detection of improving or worsening liver injury than conventional enzyme testing.

Methods
Serial serum samples collected daily from 31 patients enrolled in the Acute Liver Failure Study Group, with acetaminophen (APAP) toxicity, drug-induced liver injury, ischemic hepatopathy (IH), or autoimmune hepatitis were analyzed to determine α-GST using the Qualigen FastPack® α-GST Assay (Carlsbad), a chemiluminescent immunoassay using a paramagnetic particle matrix with an upper limit of normal of 11 ng/mL. AST and ALT values were obtained from the medical record and have an upper limit of normal of 40 IU/L. The T½ values for α-GST, AST, and ALT were calculated from the peak value for APAP and IH etiologies considered as single time point injuries, using an exponential trendline equation of the serial values.

Results
Median α-GST for all etiologies were increased on day 1, returning to normal by day 3, whereas median AST and ALT values did not return to normal, even at day 7. The median T½ for α-GST, AST, and ALT were 6.4, 22.2, and 33.9 h, respectively.

Conclusions
α-GST is a more responsive marker of liver injury/recovery, allowing for more rapid real-time assessment of improvement or worsening of liver disease.
Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS
Authors: Hummert Pamela , Manohar Madhuri , Aung Wutyi S , Marzinke Mark A 
Published: July 2018

Abstract

Background
Medroxyprogesterone acetate (MPA) is a common contraceptive agent taken both orally and as a subcutaneous or intramuscular injection. Current LC-MS/MS methods for MPA quantification require large sample volumes and low-throughput analytical run times. Therefore, there are opportunities to improve upon existing methods for MPA quantification.

Methods
MPA was extracted from 600 μL plasma, evaporated to dryness, and the reconstituted solution was injected onto a Waters Acquity liquid chromatography (LC) system via an Agilent Zorbax Eclipse-Plus C18 2.1 × 50 mm (5.0 μm) column. MPA and its internal standard were monitored on a QTRAP® 5500 mass analyzer operated in positive ionization mode. The method was validated according to the Food and Drug Administration Bioanalytical Method Validation guidelines.

Results
The analytical measuring range of the assay was 200–10 000 pg/mL. QC samples prepared at the lower limit of quantification (LLOQ; 200 pg/mL) and low (600 pg/mL), mid (1750 pg/mL), and high (8500 pg/mL) levels showed interassay precision and accuracy ≤15.2% and ≤±9.6%, respectively. Stability-challenged samples yielded ≤15% from freshly prepared samples. Dilutional and matrix effects studies were also acceptable. The assay was also assessed in participants prescribed depot medroxyprogesterone acetate; observed concentrations were within the dynamic range of the assay.

Conclusions
An LC-MS/MS method for the quantification of MPA in plasma has been developed and validated. The described method is sufficiently sensitive and robust to quantify MPA in plasma and meets the criteria to support clinical trials.