bluuebunny/crossref_metadata_2025 huggingface dataset:
“Don’t Get Above Yourself ”: Heterosexual Cross-Class Couples Are Viewed Less Favorably
Authors: MacInnis Cara C. , Buliga Elena
Published: October 2019

We examined perceptions of cross-class heterosexual couples, that is, couples where couple members differ in social class. Informed by social dominance theory, system justification theory, and equity theory, we predicted that (a) cross- (vs. same-) class couples would be perceived more negatively, (b) cross-class couples with the woman (vs. the man) in the higher class position would be evaluated more negatively, and (c) same-class low-low (vs. high-high) couples would be evaluated more negatively. We examined perceptions of cross-income, cross-education, and cross-occupation status relationships. We found support for our predicted patterns, with some exceptions. In general, high-high class couples were preferred. In three of four studies, a higher-class woman paired with a lower-class man was evaluated most negatively of all couples. Recognition of this prejudice may explain challenges faced by certain couples and couple members; as such, implications for clinicians and counselors are discussed. Further, our research generates directions for future research. Additional online materials for this article are available on PWQ’s website at http://journals.sagepub.com/doi/suppl/10.1177/0361684319878459
Media Strategies in Policy Advocacy: Tracing the Justifications for Indiana’s School Choice Reforms
Authors: Malin Joel R. , Lubienski Christopher , Mensa-Bonsu Queenstar
Published: October 2019

This study treats Indiana (2010-2018) as a case in which to examine media-based coverage, deliberation, and ethical and empirical framings as school choice reforms were being taken up and as they evolved and accelerated. Within this timeframe, Indiana transformed into a leading state in school choice reforms. Both repetitive and shifting justifications were noted, with these patterning roughly into three main phases. Arguments were much more frequently ideological than empirical in nature, and advocates generally (and especially in the first two phases) were observed as holding the upper hand, successfully using the media to frame the debate using their terms.
Teacher Power and the Politics of Union Organizing in the Charter Sector
Authors: Jabbar Huriya , Chanin Jesse , Haynes Jamie , Slaughter Sara
Published: October 2019

Despite the growing media attention paid to charter-school unions, comparatively little empirical research exists. Drawing on interview data from two cities (Detroit, MI, and New Orleans, LA), our exploratory study examined charter-school teachers’ motivations for organizing, the political and power dimensions, and the framing of unions by both teachers and administrations. We found that improving teacher retention, and thus school stability, was a central motivation for teacher organizers, whereas, simultaneously, high teacher turnover stymied union drives. We also found that charter administrators reacted with severity to nascent unionization drives, harnessing school-as-family metaphors and at-will contracts to prevent union formation. As the charter sector continues to grow, understanding why teachers want unions and how those unions differ from traditional public school unions is crucial to analyzing the long-term viability of these schools and the career trajectories of the teachers who work in them.
The effects of L-NAME on DU145 human prostate cancer cell line: A cytotoxicity-based study
Authors: Kacar S , Kar F , Hacioglu C , Kanbak G , Sahinturk V
Published: October 2019

Of all cancer types, prostate cancer is the second most common one with an age-standardized incidence rate of 29.3 per 100,000 men worldwide. Nitric oxide (NO) is both a radical and versatile messenger molecule involved in many physiological activities. NO was documented to be highly secreted and utilized by cancer cells. N ω-nitro-L-arginine methyl ester (L-NAME) is utilized for inhibiting NO synthase. Its worst long-term side effect is reported to be hypertension, hence less cytotoxic than chemotherapeutic agents. Herein, we carried out a cytotoxicity study on how different doses of L-NAME affect DU145 human prostate cancer cells. First, toxic doses of L-NAME were determined. Then, while antioxidant capacity was determined by glutathione and total antioxidant status, oxidative stress was evaluated by quantifying malondialdehyde, NO, and total oxidant status levels. Inflammatory effects of L-NAME were investigated by measuring tumor necrosis factor- α and interleukin-6 (IL-6) levels. Apoptotic effects of L-NAME were evaluated by measuring cytochrome C somatic and caspase 3 levels and by staining Bax protein. Finally, morphological analysis was performed. IC50 of L-NAME against DU145 cells was 12.2 mM. In L-NAME-treated DU145 cells, a dose-dependent increase in oxidative stress, inflammatory, and apoptotic marker proteins and decrease in antioxidant capacity were observed. While at the moderate dose of L-NAME, apoptotic changes were commonly observed, at higher doses, vacuolated and swollen cells were also recorded. We believe that the present study will encourage future studies by providing insights about dose and effects of L-NAME.
Does Public Health System Provide Adequate Financial Protection to Its Clients Through RSBY? An Exploratory Study of Tribal Odisha
Authors: Panda Babita , Rout Himanshu Sekhar
Published: October 2019

This study estimates whether Rashtriya Swasthya Bima Yojana (RSBY) protects beneficiaries from out-of-pocket health expenditure arising at the time of illness and points out obstacles that the beneficiaries face. This article uses data of 100 beneficiaries selected through simple random sampling from the beneficiaries list that were collected from the district headquarter hospital of Mayurbhanj District, Odisha, India. This study highlights that only 8.4 per cent beneficiaries access their full healthcare services from the scheme. More than 50 per cent are forced to spend from their own pocket even though they have sum assured. The beneficiaries face problems like lack of awareness, no proper enrolment procedure, no cooperative hospital staff, limited assured money sanctioned per day, only inpatient care services, an unhygienic atmosphere in the hospital, long distance to the empanelled hospital and exploitation among health service providers. Awareness may be created among insured. The behaviour of healthcare providers may be turned friendly. Immediate attention may be provided by help desk counters to the beneficiaries. The sum assured amount may be increased. The detailed receipt of hospital expenditure may be supplied to the insured at the time of discharge.
Individual Task Conflict Asymmetry and Peer Ratings of Member Effectiveness
Authors: Wang Shirley , Homan Astrid C. , Jehn Karen
Published: October 2019

The present article explores the effects of individual task conflict asymmetry—a member’s task conflict perception relative to others on the team—on peer ratings of that member’s effectiveness. In two studies of student teams, we find that individuals who perceive more conflict than their teammates are rated as more effective team members. This effect is explained by uncertainty experienced by the high task conflict perceiver, which acts as a catalyst for additional effort expansion toward team goals. By turning our attention to peer ratings of member effectiveness, we offer an optimistic side to individual task conflict asymmetry.
Augmented Reality Supporting Reading Skills of Students with Autism Spectrum Disorder
Authors: Howorth Sarah K. , Rooks-Ellis Deborah , Flanagan Sara , Ok Min Wook
Published: October 2019

Teachers’ use of video modeling has been established as an evidence-based practice for teaching students with autism spectrum disorder (ASD). Augmented reality (AR) applications can be used as tools to provide trigger-based, video-modeled instructional supports to students with ASD. The use of AR in this way may help teachers implement evidence-based reading skills practice such as video modeling and provide more independent practice opportunities. It also provides more options for student engagement and concept representation. This article describes ideas for how to use a particular AR application to (a) teach phonics and word identification, (b) support reading fluency, (c) embed videos into texts as cues for reading comprehension, (d) teach content area vocabulary words, and (e) use video models during transition planning.
Playing it Cool: Considering McLuhan’s Hot and Cool taxonomy for Game Studies
Authors: Conway Steven , Ouellette Marc
Published: October 2019

While Marshall McLuhan is often acknowledged as an influential theorist for Game Studies, there is very little work currently available that directly attempts to apply McLuhan’s theoretical framework and terminology. This article, therefore, provides an overview, interrogation and application of McLuhan’s taxonomy of Hot and Cool media to digital games. McLuhan describes Hot media as ‘high fidelity’ and ‘low participation’, while Cool media are conversely ‘high participation’ and ‘low fidelity’. The article summarizes McLuhan’s conceptual spectrum and articulates how these qualities can exist not only within digital games but also within the player: their skills, competencies and literacies. In doing so, we propose the further quality of ‘pattern’ to better describe how Hot and Cool features operate within game experiences. The article finally discusses how Hot and Cool game designs can impact user’s affective, cognitive, motoric and sociocultural responses to the play experience.
Postmillennial cancer narratives: feminism and postfeminism in Eve Ensler’s In the Body of the World
Authors: Fernández-Morales Marta
Published: October 2019

In the context of a new wave of women’s activism for equality, the body is once again at the centre of the discussion today, in the USA and globally. Analysing American discourses about health and illness at the turn of the twenty-first century, Tasha Dubriwny has argued that the current narratives are dominated by neoliberal and postfeminist philosophies that have thrived in a framework of biomedicalisation and self-surveillance. What happens, then, when a successful feminist artist is diagnosed with uterine cancer? How does Eve Ensler, author of The Vagina Monologues and founder of V-Day, face the fact that her life may have a painful ending? How does a woman so aware of her physical and psychological self come to terms with illness? Is she willing to put her political project aside to become a patient? Through a close reading of Ensler’s uterine cancer memoir In the Body of the World, and focusing particularly on its structure and narrative strategies, this article situates her work within the corpus of female literature about health and illness in the twenty-first century, exploring her meaning-making process in the light of the current tensions between feminism and postfeminism.
Radical republicanism and solidarity
Authors: Kohn Margaret
Published: October 2019

This article explains how 19th-century radical republicans answered the following question: how is it possible to be free in a social order that fosters economic dependence on others? I focus on the writings of a group of French thinkers called the solidarists who advocated “liberty organized for everyone.” Mutualism and social right were two components of the solidarist strategy for limiting domination in commercial/industrial society. While the doctrine of mutualism was rooted in pre-industrial artisan culture, social right was a novel idea that built on Durkheim’s analysis of the division of labour. In this article, I describe the main features of the solidarist account: solidarity, social property, quasi-contractual debt, and restorative justice. Classical republicanism was deeply concerned with citizen participation and the balance between popular and elite power, but 19th-century radical republicans thought that these goals must be approached differently in market societies in which enormous power is exercised outside the state. The solidarists cautiously embraced the state as a mechanism for regulating the market in order to ensure equal liberty. Social right and mutualism were also conceived as ways of limiting the centralization of state power.
A Model for the Prediction of Survival in Patients With Upper Tract Urothelial Carcinoma After Surgery
Authors: Zhang Guang-lin , Zhou Wei
Published: October 2019

Objective:

We aimed to formulate and validate prognostic nomograms that can be used to predict the prognosis of patients with upper tract urothelial carcinoma (UTUC).

Methods:

By consulting the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients who were surgically treated for UTUC between 2004 and 2013. Variables were analyzed in both univariate and multivariate analyses. Nomograms were constructed based on independent prognostic factors. The prognostic nomogram models were established and validated internally and externally to determine their ability to predict the survival of patients with UTUC.

Results:

A total of 4990 patients were collected and enrolled in our analyses. Of these, 3327 patients were assigned to the training set and 1663 to the validation set. Nomograms were effectively applied to predict the 3- and 5-year survivals of patients with UTUC after surgery. The nomograms exhibited better accuracy for predicting overall survival (OS) and cancer-specific survival (CSS) than the tumor-node-metastasis (TNM) staging system and the SEER stage in both the training and validation sets. Calibration curves indicated that the nomograms exhibited high correlation to actual observed results for both OS and CSS.

Conclusions:

The nomogram models showed stronger predictive ability than the TNM staging system and the SEER stage. Precise estimates of the prognosis of UTUC might help doctors to make better treatment decisions.
HDL-cholesterol elevation associated with fingolimod and dimethyl fumarate therapies in multiple sclerosis
Authors: Blumenfeld Kan S , Staun-Ram E , Golan D , Miller A
Published: October 2019

Background

Patients with Multiple Sclerosis (PwMS) display altered lipoproteins levels and function, which seem to affect disease risk and progress. Whether disease-modifying therapies affect the lipoprotein profile in PwMS has scarcely been studied.

Objective

The study aims to assess whether fingolimod and dimethyl fumarate (DMF) affect lipoproteins in PwMS.

Methods

We compared retrospectively the blood lipoprotein levels of 29 fingolimod-treated and 41 DMF-treated patients before and after 3 and 12 months of therapy. Patients treated with cholesterol-reducing medications were not included. Data on weight change and disease activity during 1-year follow-up were obtained.

Results

HDL level, HDL/LDL ratio and HDL/total cholesterol ratio were increased in both treatment groups after 3 months’ therapy and sustained, with no change in LDL or triglycerides. While at baseline only 26% of patients met the recommended minimum of HDL 60 mg/dl, after 3 months’ therapy, 43% of fingolimod-treated and 47% of DMF-treated patients reached the recommended level. The majority of patients had no weight reduction.

Conclusions

Fingolimod and DMF therapies are associated with a specific increase in HDL in PwMS. Further studies are required to validate these findings and their potential implication as biomarker of reduced inflammatory state and/or reduced risk of neurodegeneration or cardiovascular comorbidity.
Emergence of Fine Art Photography in Israel in the 1970s to the 1990s Through Pedagogical and Social Links with the United States
Authors: Ben-Choreen Tal-Or K.
Published: October 2019

The flourishing of photography as a tool for expressive reportage and artistic practice transformed photographic education during the mid-twentieth century. American-based academic institutions quickly established reputations in the emerging fine art field as leaders in photographic education drawing international students from diverse locations, including Israel. Many Israelis who studied photography in American institutions returned to Israel bringing with them the knowledge they had gained while abroad. This article considers the impact of American pedagogical models and social networks on the development of the Israeli photographic field. Included in this discussion is an exploration of the emergence of Israeli photography programs in institutions of higher education, photography galleries, museum collections, and exhibitions. By approaching the study through a network methodological approach, this article traces the transnational movements of individuals: photographers, program graduates, and curators in order to demonstrate the significant impact American photographic education had on the emerging Israeli photographic field.
Targeted next generation sequencing identifies a genetic spectrum of DNA variants in patients with hemiplegic migraine
Authors: Maksemous Neven , Smith Robert A , Sutherland Heidi G , Maher Bridget H , Ibrahim Omar , Nicholson Garth A , Carpenter Elisabeth P , Lea Rod A , Cader M Zameel , Griffiths Lyn R
Published: October 2019

Objective:

Hemiplegic migraine in both familial (FHM) and sporadic (SHM) forms is a rare subtype of migraine with aura that can be traced to mutations in the CACNA1A, ATP1A2 and SCN1A genes. It is characterised by severe attacks of typical migraine accompanied by hemiparesis, as well as episodes of complex aura that vary significantly between individuals.

Methods:

Using a targeted next generation sequencing (NGS) multigene panel, we have sequenced the genomic DNA of 172 suspected hemiplegic migraine cases, in whom no mutation had previously been found by Sanger sequencing (SS) of a limited number of exons with high mutation frequency in FHM genes.

Results:

Genetic screening identified 29 variants, 10 of which were novel, in 35 cases in the three FHM genes ( CACNA1A, ATP1A2 and SCN1A). Interestingly, in this suspected HM cohort, the ATP1A2 gene harboured the highest number of variants with 24/35 cases (68.6%), while CACNA1A ranked the second gene, with 5 variants identified in 7/35 cases (20%). All detected variants were confirmed by SS and were absent in 100 non-migraine healthy control individuals. Assessment of variants with the American College of Medical Genetics and Genomics guidelines classified 8 variants as pathogenic, 3 as likely pathogenic and 18 as variants of unknown significance. Targeted NGS gene panel increased the diagnostic yield by fourfold over iterative SS in our diagnostics facility.

Conclusion:

We have identified 29 potentially causative variants in an Australian and New Zealand cohort of suspected HM cases and found that the ATP1A2 gene was the most commonly mutated gene. Our results suggest that screening using NGS multigene panels to investigate ATP1A2 alongside CACNA1A and SCN1A is a clinically useful and efficient method.
Development of Hematopoietic Stem Cells in the Human Embryo
Authors: Medvinsky Alexander
Published: October 2019

Haematopoietic stem cells (HSCs) develop intra-embryonically in the aorta-gonad-mesonephros (AGM) region, more specifically in the ventral domain of the embryonic dorsal aorta. This process is highly conserved across vertebrate species. Key transcription factors and signalling pathways involved in HSC development have been identified using various model organisms. As a mammal, the mouse represents an excellent model for understanding HSC development in the human embryo. However, in utero development significantly reduces accessibility of the embryo for experimentation, which hampers analysis of dynamic developmental processes.

We have overcome this hurdle by establishing AGM in vitro systems that can recapitulate in vivo HSC development. The generation of HSCs during embryonic development is a highly specific process. So far any significant expansion of HSCs from adult sources using solely external molecular cues have been largely unsuccessful. This is despite the fact that there is a pressing need to supply clinically relevant HSCs to some groups of patients. The generation of HSCs from pluripotent stem cells (ES/iPS cells) holds great hopes for regenerative medicine, however, this goal has not been achieved without genetic manipulations due to poor understanding of mechanisms acting in the embryo.

Using a dissociation-reaggregation AGM culture system enabled developmental hierarchy of developing mouse HSCs to be reconstructed. On co-aggregation with AGM stroma or OP9 cells, embryonic precursors mature into adult definitive HSCs, which can provide multi-lineage long-term repopulation upon transplantation into adult irradiated recipients. We have established that during development, mouse HSCs mature through upregulation CD41, CD43 and CD45 haematopoietic markers. The analysis of the AGM niche revealed a highly heterogeneous signalling landscape that can regulate HSC development in a concerted manner.

During human development, HSCs also emerge first in the ventral domain of the embryonic dorsal aorta and reside in a population, which express markers known from mouse HSC development. These first HSCs emerge in small numbers, possess an enormous regenerative/ self-renewing potential and can generate hundreds of fully functional daughter HSCs. However, it appears that establishing human AGM cultures, which recapitulate HSC development because of yet unclear reasons, is problematic. This makes it difficult to study the developing human HSC hierarchy and AGM stromal factors driving HSC development.

In this talk, commonalities and differences in mouse and human development as well as routes to the solution of this hurdle will be discussed.

Disclosures

No relevant conflicts of interest to declare.
Weight-Based Enoxaparin Dosing for Venous Thromboembolism (VTE) >100kg Gives Similar Anti-Xa Levels to Patients <100kg, with No Increase in Bleeding
Authors: Maclachlan Kylee H , Stevens Hannah P , Chunilal Sanjeev D , Tran Huyen A
Published: October 2019

Background: In clinical trials assessing venous thromboemobolism (VTE) management, patients with obesity are under-represented or specifically excluded. The International Society on Thrombosis and Haemostasis advises against direct-acting oral anticoagulants in patients >120kg(1). Therefore, low-molecular weight heparin and warfarin remain the standard of care in this population.

Objective : To assess weight-based enoxaparin dosing in VTE, with no capping of prescribed doses, comparing patients weighing >100kg with those weighing <100kg. The primary outcome was anti-Xa activity levels, as a surrogate marker of bleeding and recurrence risk, with the secondary outcome measures of major bleeding and VTE recurrence at 30 days.

Methods: A 5-year retrospective audit of patients with acute VTE who were prescribed enoxaparin at 1mg/kg BD, with an anti-Xa level taken 2-6 hours post-dose. Patients with an eGFR <30 were excluded.

Results: 166 patients weighing >100kg with acute VTE were identified, and 63 were excluded for not fulfilling all criteria. 64 patients weighing <100kg were assessed for comparison. Table 1 describes the patient characteristics, anti-Xa levels and clinical outcomes for patient above and below 100kg. Figure 1 demonstrates the anti-Xa levels in group 1 according to weight, and the distribution of anti-Xa levels below, within and above the therapeutic range (0.5-1.0U/mL).

Discussion: Patients above and below 100kg dosed with 1mg/kg enoxaparin BD showed no significant difference in either median anti-Xa levels, or distribution of anti-Xa activity. Regardless of weight, the majority of patients with an eGFR of 30-59 mL/min had anti-Xa levels >1.0U/mL. The obese patients did not suffer any major bleeding or VTE recurrence within 30 days. In comparison, the patients weighing <100kg, despite similar levels of anticoagulation, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and concurrent cancer. These findings are consistent with the observation that bleeding risk is primarily determined by clinical characteristics rather than the anti-Xa activity alone.

Conclusion: These data support a weight-based dosing strategy for enoxaparin in obese patients with VTE, with no dose-capping, to ensure therapeutic drug levels. Routine anti-Xa levels in patients weighing >100kg, particularly in those with moderate renal impairment, allow tailoring of doses to the therapeutic anti-Xa range.

Reference:

(1) Martin K et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. Journal of thrombosis and haemostasis 2016; 14: 1308-13.

Disclosures

No relevant conflicts of interest to declare.
Loss of Gadd45b Accelerates BCR-ABL-Driven CML
Authors: Sha Xiaojin , Liebermann Dan , Hoffman Barbara
Published: October 2019

Gadd45b is a member of Gadd45 stress sensor protein family that also includes Gadd45a & Gadd45g. To investigate the effect of Gadd45b in bcr-abl oncogene driven chronic myeloid leukemia (CML) development, syngeneic wild type lethally irradiated mice were reconstituted with either wild type or Gadd45b null myeloid progenitors transduced with a retroviral vector expressing BCR-ABL. Loss of Gadd45b was observed to accelerate BCR-ABL driven CML development with shortened median mouse survival time. BCR-ABL Gadd45b deficient CML progenitors exhibited increased proliferation and decreased apoptosis, associated with hyper-activation of c-Jun NH2-terminal kinase and Stat5. These results provide novel evidence that gadd45b, like gadd45a, functions as a suppressor of BCR-ABL driven leukemia, albeit via a different mechanism.

Disclosures

No relevant conflicts of interest to declare.
Developing the Next Generation of iPSC Cell-Based Immunotherapies
Authors: Vizcardo Raul , Klemen Nicholas Donald , Islam Rafiqul , Gurusamy Devikala , Tamaoki Naritaka , Jia Li , Yu Zhiya , Hennings Amanda N , Maeda Takuya , Bosch-Marce Marta , Good Meghan L , Pack Svetlana , Stroncek David F. , Flomerfelt Francis A , Kruhlak Michael J , Restifo Nicholas Phillip
Published: October 2019

T cells are potentially curative for patients with metastatic cancer, but many patients with cancer have T cells that are 'terminally differentiated', a condition associated with treatment failure. We have observed that less differentiated T cells have a greater capacity to proliferate, persist and destroy large cancer deposits. Advances in regenerative medicine might allow the generation of rejuvenated T cells from induced pluripotent stem cells (iPSC). We have previously reported that T cells can be generated from iPSC in vitro by co-culturing them OP9 stromal cells expressing Notch-1 ligand, Delta-like-1 (OP9/DLL1). These cells have limited tumor-specificity but also exhibit unconventional and NK cell-like properties demonstrating lineage diversion into alternative lymphoid development pathways, with unknown consequences for their safety and efficacy. To generate iPSC-derived T cells with more naturalistic tumor-specific T cell programs, we sought to restore physiologic signals for selection, maturation and survival. We employed a novel 3D thymic culture system using fetal thymic tissue and generated a novel type of T cell, 'iPSC-derived thymic emigrants' (iTE). Antigen-specific CD8αβ+ iTE exhibited functional properties in vitro that were almost indistinguishable from natural naïve CD8αβ+ T cells, including vigorous expansion and robust anti-tumor activity. iPSC-derived immature T cells generated using OP9/DLL1 and 'educated' in fetal thymic organoids in a 3D culture system resembled naturally-occurring 'young' T cells, as analyzed using whole genome RNA-seq techniques. iTE recapitulated many of the transcriptional programs of naïve T cells in vivo and revealed a striking capacity for engraftment, memory formation and efficient tumor destruction. Although many milestones remain, our data show that 'Next-Gen' autologous tumor-specific T cells can realistically be generated from iPSC using 3D thymic organ tissue. Our next goal is now to employ these cells to treat patients with metastatic cancer because iPSC-derived T cells have a potentially unlimited capacity for proliferation, engraftment and anti-tumor activity.

Disclosures

Vizcardo: NCI: Patents & Royalties: International Patent Application PCT/US2017/65986. Klemen:NIH/NCI: Patents & Royalties: International Patent Application PCT/US2017/65986. Restifo:NIH/NCI: Patents & Royalties: International Patent Application PCT/US2017/65986.
The Diagnostic Value of Kappa/Lambda Ratios Determined By Flow Cytometric Analysis of Peripheral Blood and Bone Marrow Specimens in B-Cell Chronic Proliferative Disease
Authors: Paiva Aldair Sousa , Jardim Alessandra Suelen , Soares Victor lima , Paiva Hugo Diogenes De Oliveira , Bahia Frank , Sales Valéria SF , Leão Marcos Dias , Silva Antonia Eduarda Martins Oliveira Elói , Lima João Pedro Andrade , Cavalcanti Geraldo Barroso
Published: October 2019

Background. Previous studies have suggested that analysis of the distribution of surface immunoglobulin light chain kappa and lambda by flow cytometry (FC) provides evidence for monoclonality of B cell tumors in patients with persistent lymphocytosis. The objective is this study is to investigate the efficiency of FC in determination of monoclonality in patients with persistent lymphocytosis through the analysis of kappa and lambda light chain of immunoglobulin expression (kappa/lambda tests). Methods: Samples of peripheral blood from 43 patients with B-CLD were analyzed. They were analyzed by FC with monoclonal antibody panel as: CD3, CD4, CD5, CD8, CD10, CD19, CD22, CD20; CD103; FMC7; CD23, CD25, CD38, CD45, CD16/CD56, HLADR, anti- heavy chain of immunoglobulin (IgH), anti-heavy chain m and d of immunoglobulin (IgM/IgD) and anti-light chains (kappa and lambda) of immunoglobulin. In addition, information about sex, age and clinical and hematological data from the patients were also evaluated. Results. A relation between kappa / lambda higher than 10:1 was found in all samples, suggesting a monoclonal B cells proliferation with 86% of the samples displayed kappa light chain of immunoglobulin expression and 14% displayed lambda light chain of immunoglobulin expression. The immunophenotyping data associated with the hematological and clinical ones, confirmed 35 cases of B-cell chronic lymphocytic leukemia, 3 cases of B-cell prolymphocytic leukemia, 3 of hairy cell leukemia, one case of Waldenstrong macroglobulinemia and mantle cell lymphoma. Conclusions. The results showed that the kappa and lambda light chain of immunoglobulin expression analysis by FC is a simple and effective methodology in the malignant B- cell proliferation.

Disclosures

No relevant conflicts of interest to declare.
Prognostic Value of DNA Index By Flow Cytometry for Minimal Residual Disease in Childhood B-Cell Acute Lymphoblastic Leukemia
Authors: Cervantes Elizabeth , Enriquez Daniel J , Vidal Judith , Retamozo Rosario
Published: October 2019

Background: Prognostic factors in B-ALL represent a critical role for treatment stratification. High hyperdiploids (>50 chromosomes) have been related to better outcomes, and hypodiploids to worse prognosis. DNA Index (DI) quantifies the DNA from leukemic blast by flow cytometry and has been correlated to the number of chromosomes. Our aim was to demonstrate the prognostic value of DI for minimal residual disease in childhood B-ALL.

Methods: 26 blood samples from newly diagnosed childhood B-ALL cases were analyzed between November 2017 and February 2018. DI was evaluated by flow cytometry in samples with Propidium Iodide and leukemic blasts were identified by CD19/CD22/CD10/CD20 antibodies. DI was calculated as the ratio of mean fluorescence of pathologic B blasts and normal cells (T, NK lymphocytes, neutrophils and monocytes) in G0/G1 phase. We stablished three categories: diploid (0.95 - 1.05, 46 chromosomes), hypodiploid (<0.95) and hyperdiploid (>1.05). 8-colors FacsCanto II BD flow cytometer was also used to evaluate minimal residual disease with 0.0025% threshold of detection.

Results: 26 cases were evaluated and 2 died during induction treatment. Median age was 8 years (4mo - 16years) and 54% were males. At diagnosis, 62% showed DI diploid and 38% DI hyperdiploid, no hypodiploids cases were detected. Clinical characteristics were similar between both groups. Median DI in the hyperdiploids cases was 1.25 (R: 1.12 - 1.64). We only detected two hyperdiploids cases by conventional karyotype. All patients received the same BFM-based protocol. After induction, all cases achieved complete remission and 46% had MRD negative at the 28th day. DI diploid and hyperdiploid cases achieved 47% and 44% MRD negative, respectively. At the end of consolidation (R: 6-8 Mo), 77% cases achieved MRD negative, and between categories, 62% of DI diploid cases had MRD negative and 100% of DI hyperdiploid cases were negative for MRD detection by flow (p=0.02).

Conclusions: The hyperdiploid DNA index by flow cytometry is associated with minimal residual disease negative at the end of consolidation.Flow cytometry offers an alternative over the conventional karyotype to detect good prognosis groups among B-ALL cases.

Disclosures

No relevant conflicts of interest to declare.
A Retrospective Case Series Describing the Efficacy of Ketotifen in Systemic Mastocytosis
Authors: Slapnicar Calum Anthony , Scullion Smeenk Conrad , Hicks Lisa K. , Petrucci Jessica , Vadas Peter , Trinkaus Martina
Published: October 2019

Introduction

Systemic Mastocytosis (SM) represents a heterogeneous group of disorders characterized by the accumulation of neoplastic mast cells (MCs) in one or more organ systems. Patients with SM present with a broad range of symptoms resulting from excessive mast cell mediator release, especially histamine that frequently overlap with those of allergic disease. Episodes of life-threatening anaphylaxis are a recognized feature of SM. Here at St. Michael's Hospital, we currently follow more than 50 SM patients, the largest patient cohort in Canada. Ketotifen is a dual action mast cell stabilizer used to treat asthma, anaphylaxis and other mast cell, allergic-type disorders. Along with cromolyn, another mast cell stabilizer, ketotifen is known to be the most effective at controlling mast cell activation. At St. Michael's Hospital, ketotifen is used as an add-on, off-label therapy in SM patients at risk for recurrent anaphylaxis. The literature has yet to confirm the efficacy of using ketotifen to treat SM. Few centres besides St. Michael's use ketotifen as a potential therapy.

Objectives

Our primary objective was to describe the response to treatment by ketotifen in patients with SM in a tertiary care centre.

Methods

This is an observational, retrospective study (n=10) of SM patients treated with ketotifen at St. Michael's Hospital from January 2015 to June 2018. Electronic medical records were reviewed for mastocytosis treatment and symptom progression. All patients included in the study were diagnosed with SM according to the 2016 WHO criteria by undergoing a bone marrow biopsy. Symptoms were assessed at baseline (2-5 months pre-ketotifen initiation) and again at follow-up (4-8 months post initiation). An independent statistician produced binomial proportion confidence intervals for each reported symptom.

Results

Our study consisted of 7 females and 3 males, with an average age of 49 years old [IQR 33-67]. 5 of the 10 patients were diagnosed with indolent SM, the more moderate of the six SM subtypes. Table 1 demonstrates the 5 most frequently reported symptoms at baseline.

(Refer to Table 1) For nausea/vomiting, presyncope/syncope and urticaria, 100% of patients who reported these symptoms responded to treatment. For diarrhea and flushing, 86% and 67% of patients who reported these symptoms responded to treatment.

Conclusions

Ketotifen appears to be an effective therapy for patients with SM with anaphylaxis. It should be readily considered in the management of this population. Further investigation is warranted given our small sample size and single centre recruitment. Next steps include following these patients prospectively to better capture the efficacy of ketotifen within this population.

Disclosures

No conflicts of interest to declare

Disclosures

No relevant conflicts of interest to declare.
Methamphetamine use association with pulmonary diseases: a retrospective investigation of hospital discharges in California from 2005 to 2011
Authors: Tsai Halley , Lee Justin , Hedlin Haley , Zamanian Roham T. , de Jesus Perez Vinicio A.
Published: October 2019

Background

Methamphetamine can have acute and long-term adverse health consequences. Our objective was to determine whether methamphetamine use is associated with more hospitalisation codes for asthma exacerbation, chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia and acute respiratory failure (ARF).

Methods

The Health Care Utilization Project (HCUP) database includes retrospective inpatient discharge abstracts from 2005 through 2011 from the California state inpatient databases (SIDs). ICD-9 codes were used to identify hospitalisations for asthma exacerbation, COPD exacerbation, acute pneumonia, ARF and methamphetamine use from discharges with complete demographic data and ages 18 to 75 years. Adjusted rate ratios comparing methamphetamine users with nonusers were estimated separately for each pulmonary disease diagnosis by sex using negative binomial regression models.

Results

We included 21 125 249 inpatient discharges from 2005 through 2011 in California in our analysis; 182 766 (0.87%) had methamphetamine use. The rate ratio comparing pneumonia in discharges with methamphetamine useversusthose without were 1.40 (95% CI 1.18, 1.67) for women and 1.18 (95% CI 1.04, 1.35) for men; comparing ARF 1.77 (95% CI 1.59, 1.98) for women and 1.24 (95% CI 1.12, 1.37) for men; and comparing COPD exacerbation 1.40 (95% CI 1.18, 1.67) for women and 0.90 (95% CI 0.79, 1.02) for men.

Conclusions

A positive association was found when comparing inpatient hospital discharge diagnoses for methamphetamine use and those for pneumonia and ARF in both sexes. This association was not seen when comparing discharge diagnoses for methamphetamine and those for asthma exacerbation in both sexes or COPD exacerbation in men. While future investigation for is warranted, this finding may help to further characterise the pulmonary toxicity of methamphetamine.
The Initiation of Inferior Grain Filling is Affected by Sugar Translocation Efficiency in Large Panicle Rice
Authors: Chen Lin , Deng Yao , Zhu Honglei , Hu Yuxiang , Jiang Zhengrong , Tang She , Wang Shaohua , Ding Yanfeng
Published: October 2019

Background

Large panicle rice has a large sink capacity, but inferior spikelet filling is poor in this variety of rice due to asynchronous grain filling. The understanding of the factors that cause asynchronous grain filling will help to propose a model for how to regulate the rice inferior spikelets grain filling.

Results

In this study, two large panicle rice varieties, W1844 and CJ03, with the same sink capacity but with differences in asynchronous grain filling were used. The difference in the grain filling rate between superior and inferior spikelets in W1844 was much smaller than that in CJ03. We found that superior spikelet filling was initiated earlier in W1844 than in CJ03. The source-to-sink translocation rate of sucrose during the grain filling stage was more efficient in W1844 than in CJ03, and the gene expression levels of sucrose transporters (OsSUTs) were higher in W1844 functional leaves than in those of CJ03. In addition, carbon output, the transport ratio, and the contribution rate from the stem and sheath to the panicle were much higher at the early filling stage than at later filling stages in W1844.

Conclusion

Efficient sugar translocation can satisfy high sink strength, and also the strong sink activity can facilitate the sugar unloading in spikelets. All the above results indicate that an efficient sugar translocation rate at the early grain filling stage can improve sink strength and inferior grain filling initiation. Strategies to limit asynchronous grain filling in rice were also discussed based on our findings.
Comprehensive Transcriptomic Analysis of Mouse Gonadal Development Involving Sexual Differentiation, Meiosis and Gametogenesis
Authors: Wang Jian , Tian Geng G. , Zheng Zhuxia , Li Bo , Xing Qinghe , Wu Ji
Published: October 2019

Background

Mammalian gonadal development is crucial for fertility. Sexual differentiation, meiosis and gametogenesis are critical events in the process of gonadal development. Abnormalities in any of these events may cause infertility. However, owing to the complexity of these developmental events, the underlying molecular mechanisms are not fully understood and require further research.

Results

In this study, we employed RNA sequencing to examine transcriptome profiles of murine female and male gonads at crucial stages of these developmental events. By bioinformatics analysis, we identified a group of candidate genes that may participate in sexual differentiation, including Erbb3, Erbb4, and Prkg2. One hundred and two and 134 candidate genes that may be important for female and male gonadal development, respectively, were screened by analyzing the global gene expression patterns of developing female and male gonads. Weighted gene co-expression network analysis was performed on developing female gonads, and we identified a gene co-expression module related to meiosis. By alternative splicing analysis, we found that cassette-type exon and alternative start sites were the main forms of alternative splicing in developing gonads. A considerable portion of differentially expressed and alternatively spliced genes were involved in meiosis.

Conclusion

Taken together, our findings have enriched the gonadal transcriptome database and provided novel candidate genes and avenues to research the molecular mechanisms of sexual differentiation, meiosis, and gametogenesis.
doepipeline: a systematic approach to optimizing multi-level and multi-step data processing workflows
Authors: Svensson Daniel , Sjögren Rickard , Sundell David , Sjödin Andreas , Trygg Johan
Published: October 2019

Background

Selecting the proper parameter settings for bioinformatic software tools is challenging. Not only will each parameter have an individual effect on the outcome, but there are also potential interaction effects between parameters. Both of these effects may be difficult to predict. To make the situation even more complex, multiple tools may be run in a sequential pipeline where the final output depends on the parameter configuration for each tool in the pipeline. Because of the complexity and difficulty of predicting outcomes, in practice parameters are often left at default settings or set based on personal or peer experience obtained in a trial and error fashion. To allow for the reliable and efficient selection of parameters for bioinformatic pipelines, a systematic approach is needed.

Results

We presentdoepipeline, a novel approach to optimizing bioinformatic software parameters, based on core concepts of the Design of Experiments methodology and recent advances in subset designs. Optimal parameter settings are first approximated in a screening phase using a subset design that efficiently spans the entire search space, then optimized in the subsequent phase using response surface designs and OLS modeling.Doepipelinewas used to optimize parameters in four use cases; 1) de-novo assembly, 2) scaffolding of a fragmented genome assembly, 3) k-mer taxonomic classification of Oxford Nanopore Technologies MinION reads, and 4) genetic variant calling. In all four cases,doepipelinefound parameter settings that produced a better outcome with respect to the characteristic measured when compared to using default values. Our approach is implemented and available in the Python packagedoepipeline.

Conclusions

Our proposed methodology provides a systematic and robust framework for optimizing software parameter settings, in contrast to labor- and time-intensive manual parameter tweaking. Implementation indoepipelinemakes our methodology accessible and user-friendly, and allows for automatic optimization of tools in a wide range of cases. The source code ofdoepipelineis available athttps://github.com/clicumu/doepipelineand it can be installed through conda-forge.
Identification of differentially expressed genes and pathways between intramuscular and abdominal fat-derived preadipocyte differentiation of chickens in vitro
Authors: Zhang Meng , Li Fang , Ma Xiang-fei , Li Wen-ting , Jiang Rui-rui , Han Rui-li , Li Guo-xi , Wang Yan-bin , Li Zi-yi , Tian Ya-dong , Kang Xiang-tao , Sun Gui-rong
Published: October 2019

Background

The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens.

Results

AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes(86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such asPPARG,ACSBG2,FABP4,FASN,APOA1andINSIG1, were identified in our study.

Conclusion

This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.