bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA05: Genomic approaches to drug discovery
Authors: Golub Todd
Published: August 2018

It is now becoming possible to bring powerful genomic methods to bear on the process of drug discovery. This talk will illustrate 1) the use of the Connectivity Map, a large-scale effort to develop a compendium of gene expression signatures of cellular state; 2) the use of PRISM, a new multiplexed, high-throughput approach to screening cancer cell lines for anticancer activity; and 3) the use of cancer models (cell lines and patient-derived xenografts) in discovery, with particular focus on clonal drift in these models and the impact of that drift on drug sensitivity.

Citation Format: Todd Golub. Genomic approaches to drug discovery [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA05.
Abstract IA07: Cancer drug target identification using domain-focused CRISPR screening
Authors: Vakoc Christopher
Published: August 2018

In my presentation, I will describe an experimental strategy to reveal actionable protein domains that sustain the growth of cancer cells, which relies on CRISPR-Cas9-based indel mutagenesis of exons encoding protein domains.

Citation Format: Christopher Vakoc. Cancer drug target identification using domain-focused CRISPR screening [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA07.
Abstract IA18: Integrin-α10 drives metastasis and sarcomagenesis in mxyofibrosarcoma and undifferentiated pleomorphic sarcoma
Authors: Singer Samuel
Published: August 2018

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are the most common and aggressive types of genetically complex sarcoma. The development of new targeted therapies is vital for improving patients' outcomes; however, the complexity of alterations in these sarcomas has made it difficult to find the true drivers of oncogenesis. To investigate the molecular basis of MFS and UPS oncogenesis and progression, we undertook gene expression and copy number profiling of a well-characterized set of 94 primary untreated high-grade MFS and UPS. Unsupervised clustering identified a subgroup associated with poor clinical outcome. This subgroup had strikingly higher expression of the integrin-α10 gene, ITGA10, and its expression was also independently associated with outcome. We therefore investigated the role of integrin-α10 in MFS and UPS cells, defined the pathways by which it exerts its effects, and tested pharmacologic inhibition of these pathways for antitumor effects both in vitro and in vivo. Silencing of integrin-α10 induces growth suppression through apoptosis in MFS and UPS cells but not in normal mesenchymal cells. Integrin-α10 transmitted its tumor-specific signal via TRIO and RICTOR, two oncoproteins that are frequently co-overexpressed through gene amplification on chromosome 5p. TRIO and RICTOR activated RAC/PAK and AKT/mTOR to promote sarcoma cell survival. Inhibition of these proteins with EHop-016 (RAC inhibitor) and INK128 (mTOR inhibitor) had antitumor effects in tumor-derived cell lines and mouse xenografts, and combining the drugs enhanced the effects. Our results demonstrate the importance of integrin-α10/TRIO/RICTOR signaling for driving myxofibrosarcoma progression and provide the basis for promising targeted treatment strategies for patients with high-risk disease.

Citation Format: Samuel Singer. Integrin-α10 drives metastasis and sarcomagenesis in mxyofibrosarcoma and undifferentiated pleomorphic sarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA18.
Abstract IA23: Variation in the immune cell infiltrate and expression of PD-L1 in sarcoma subtypes
Authors: Andrulis Irene L.
Published: August 2018

The presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment has been associated with clinical characteristics and prognosis in various cancers, although the role of TILs in sarcoma is unclear. Adult soft tissue sarcomas are a heterogeneous group of tumors that would benefit from the identification of new prognostic markers and novel therapeutic strategies. The purpose of this study was to determine whether there are specific subgroups of soft tissue sarcomas that contain TILs and/or express immune checkpoint proteins, and if so, the clinical importance. We performed immunohistochemistry (IHC) on sections from 99 tumors and found that certain soft tissue sarcomas such as leiomyosarcoma and liposarcoma exhibit little or no immune infiltrate and immune checkpoint proteins. In contrast, a subset of undifferentiated pleomorphic sarcomas (UPS) and myxofibrosarcomas contain TILs and express PD-L1 and PD-1. Evaluation of expression of PD-L1 by IHC has been controversial; however, we observed a significant positive correlation comparing the levels of PD-L1 determined by IHC on tumor sections and RT-qPCR of mRNA from quick frozen primary tumors. We detected PD-L1 expression in a well-characterized group of osteosarcomas in addition to UPS and myxofibrosarcoma. We are now integrating data from RNA-sequencing and next-generation sequencing to investigate the molecular differences in tumors with and without PD-L1 expression. These studies suggest that there may be individuals with specific sarcomas who may be good candidates to benefit from immunotherapies targeting PD-L1/PD-1 based on their tumor characteristics.

Citation Format: Irene L. Andrulis. Variation in the immune cell infiltrate and expression of PD-L1 in sarcoma subtypes [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA23.
Abstract PR10: Development and characterization of novel/genetically defined mouse models of malignant peripheral nerve sheath tumor for preclinical therapeutics testing
Authors: Patel Amish J. , Sher Jessica J. , Chen Yu , Chi Ping
Published: August 2018

Malignant peripheral nerve sheath tumor (MPNST) represents 5-10% of soft-tissue sarcomas, and can develop either sporadically, in patients with neurofibromatosis Type I (NF1), or in association with radiotherapy. Limited genetic information regarding their pathogenesis in humans has posed a challenge to developing authentic mouse models more reflective of the human disease. Recently, we discovered that these clinically distinct MPNST subtypes commonly share inactivating mutations in tumor suppressors NF1, CDKN2A, and PRC2 (Polycomb Repressive Complex 2). Using a combination of Cre-loxP-based genetically engineered mouse models (GEMMs) and stem/progenitor transplantation models, we show that inactivation of these tumor suppressors is sufficient to promote development of bona fide MPNSTs. We envision that further characterization of these models will provide a solid foundation for investigating MPNST biology and developing therapies in a genetically defined context more closely resembling the human disease.

This abstract is also being presented as Poster B18.

Citation Format: Amish J. Patel, Jessica J. Sher, Yu Chen, Ping Chi. Development and characterization of novel/genetically defined mouse models of malignant peripheral nerve sheath tumor for preclinical therapeutics testing [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR10.
Abstract PR14: Immune cell transcript levels, metastatic progression, and survival in osteosarcoma: A comparative transcriptome analysis
Authors: Scott Milcah , Temiz Nuri , Sarver Anne , LaRue Rebecca , Rathe Susan , Varshney Jyotika , Wolf Natalie , Moriarity Branden , Obrien Timothy , Spector Logan , Largaespada David , Modiano Jaime , Subramanian Subbaya , Sarver Aaron
Published: August 2018

Background: Human osteosarcoma (OS) is a rare bone disease primarily affecting children and adolescents that has proven challenging to study, due both to its rarity and its genetic heterogeneity. OS is very common in large-breed dogs and can be genetically induced in mice, making the disease ideal for comparative genomic analyses across species. The overall survival rate of patients with OS is ~60% in patients under 30 years old and only ~30% for patients aged 50 years or older---rates that have not significantly improved over the past two decades. Understanding how intertumor transcriptional variation is conserved across species and associated with progression to metastasis resulting in patient death will enable us to more efficiently develop effective strategies to manage OS and improve therapy.

Methods and Findings: Transcriptional profiles of OS tumors and cell lines derived from humans (n=49), mice (n=103), and dogs (n=34) were generated using RNA sequencing. We identified conserved intertumor transcriptional variation present in tumor sets from all 3 species, comprising gene clusters associated with cell cycle/mitosis and with the presence/absence of immune cells. Further, we developed a novel Gene Cluster Expression Summary Score (GCESS) technique to quantify intertumor transcriptional variation and demonstrate that these GCESS values are

associated with patient outcome. Specifically, we show that human OS tumors with GCESS values indicative of decreased immune cell presence are associated with metastasis and poor survival. These results were validated in an independent human OS tumor cohort and in 15 different tumor data sets obtained from The Cancer Genome Atlas (TCGA).

Conclusions: Utilizing GCESS-based analyses of primary OS tumors to characterize the extent to which immune cells are absent and the tumor cells are undergoing mitosis may provide key information to identify novel drug targets, better inform therapeutic decisions, and improve overall survival for OS patients.

This abstract is also being presented as Poster A07.

Citation Format: Milcah Scott, Nuri Temiz, Anne Sarver, Rebecca LaRue, Susan Rathe, Jyotika Varshney, Natalie Wolf, Branden Moriarity, Timothy Obrien, Logan Spector, David Largaespada, Jaime Modiano, Subbaya Subramanian, Aaron Sarver. Immune cell transcript levels, metastatic progression, and survival in osteosarcoma: A comparative transcriptome analysis [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR14.
Pre-Induction Transperineal Ultrasound Assessment for the Prediction of Labor Outcome
Authors: Chan Winnie W.Y. , Chaemsaithong Piya , Lim Wen Teng , Tse Ada W.T. , Kwan Angel H.W. , Leung Tak Yeung , Sahota Daljit S. , Poon Liona C.
Published: August 2018

Objective: To examine (1) the concordance of manual and automated para-symphyseal angle of progression (psAOP) measurements, (2) the repeatability of psAOP, head-symphysis distance, head-perineum distance, and sonographic cervical dilatation, and (3) the value of transperineal ultrasound (TPU) in predicting induction of labor (IOL) outcome. Methods: We performed a prospective study in 308 women with singleton pregnancies undergoing IOL at term. Logistic regression analysis was used to determine which maternal factors, Bishop score, method of IOL, and TPU parameters were significant predictors of cesarean section (CS) and CS due to no progress (CS-NP). Results: There was vaginal delivery in 225 (83.0%) and CS in 46 (17.0%) cases. The intra-class correlation coefficient between manual and automated psAOP was 0.866, but automated psAOP was 4.6° wider than manual measurement. All TPU parameters had an inter-observer intra-class correlation coefficient > 0.800. Significant independent prediction of CS and CS-NP was provided by maternal factors, previous vaginal delivery, and psAOP. There was no improvement in area under the receiver-operating characteristic curve with the addition of psAOP to maternal factors. Conclusions: All TPU parameters are reproducible. Comparing the three TPU parameters for fetal head station, only psAOP is a significant independent predictor of CS; however, it is unlikely to be useful in predicting IOL outcome.
The Effect of Chorionicity on Maternal Cardiac Adaptation to Uncomplicated Twin Pregnancy: A Prospective Longitudinal Study
Authors: Ghi Tullio , Dall’Asta Andrea , Franchi Laura , Fieni Stefania , Gaibazzi Nicola , Siniscalchi Carmine , Pedrazzi Giuseppe , Montaguti Elisa , Degli Esposti Daniela , Carpano Maria Giovanna , Suprani Alice , Orabona Rossana , Prefumo Federico , Vizzardi Enrico , Bonadei Ivano , Sciatti Edoardo , Borghi Claudio , Frusca Tiziana
Published: August 2018

Objective: The objective of this study was to longitudinally evaluate maternal echocardiographic findings in uncomplicated twin gestations according to chorionicity. Methods: Healthy women with twin pregnancy were assessed with transthoracic echocardiography across the first, second, and third trimesters. Cardiac findings were compared within each group and between monochorionic (MC) and dicho­rionic (DC) pregnancies. Results: Overall, 19 MC and 48 DC uncomplicated twin pregnancies were included. In the MC group, no significant maternal haemodynamic changes were documented across gestation, with the exception of a decrease in ejection fraction. Compared to DC pregnancies, in the MC set lower cardiac output (second and third trimester, p = 0.001 and p = 0.006, respectively) and higher total vascular resistance (first trimester, p = 0.032) were observed. Regarding the diastolic function in MC twins, significantly higher values were observed for mitral E/A ratio (third trimester, p = 0.014), septal mitral E1/A1 ratio (third trimester, p = 0.030), lateral mitral E1 (second and third trimester, p = 0.014 and p = 0.029, respectively), and E1/A1 ratio (third trimester, p = 0.006). Conclusions: Maternal cardiac adaptation in twin pregnancy seems to differ significantly according to chorionicity. In particular, in MC pregnancies the impairment of diastolic function is less pronounced, presumably due to the lower circulating volume.
Urine Cofilin-1 Detection for Predicting Type 1 Cardiorenal Syndrome in the Coronary Care Unit: A Gold Nanoparticle- and Laser-Based Approach
Authors: Chen Hsing-Yu , Chou Chien , Chang Chih-Hsiang , Lee Nien-Gen , Yu Pei-Chun , Chen Yu-Chi , Pan Heng-Chih , Fan Pei-Chun , Yang Chih-Wei , Cherng Wen-Jin , Chen Yung-Chang
Published: August 2018

Background: Type 1 cardiorenal syndrome (CRS) is a severe complication for acute decompensated heart failure patients. This study aimed at evaluating the feasibility of using the gold nanoparticle-based localized surface plasmon-coupled fluorescence biosensor (LSPCFB) to detect urine cofilin-1 as a biomarker for predicting CRS among patients in the coronary care unit (CCU). Methods: A total of 44 patients were included with prospectively collected urine and blood samples. Both LSPCFB and conventional enzyme-linked immunosorbent assays (ELISAs) were used to measure urine cofilin-1 at admission to the CCU. The occurrence of CRS was judged within 7 days after admission. The discrimination presented as the area under the receiver operating characteristic curve (AUROC) and calibration of both detection methods were used to assess the predictive ability of urine cofilin-1 measured by the LSPCFB and ELISA. Results: Thirteen patients were diagnosed with CRS, while the other 31 patients were classified into a non-CRS group. For predicting CRS by measuring urine cofilin-1, the LSPCFB had higher accuracy (AUROC: 0.707, p = 0.031; overall accuracy: 79.55%) than the ELISA (AUROC: 0.479, p = 0.827; overall accuracy: 53.27%). The positive and negative predictive values of the LSPCFB were also higher than those of the ELISA (positive predictive value: 70.0 vs. 34.8%; negative predictive value: 82.4 vs. 76.2%). Conclusions: The gold nanoparticle-based immunoassay LSPCFB could exploit the potential of urine cofilin-1 as a single biomarker to predict CRS among CCU patients.
Acute Myeloid Leukemia with Myelodysplasia-Related Changes in a Patient with Crohn’s Disease Treated with Immunosuppressive Therapy
Authors: Li Bowen , Zhu Zhenhua , Long Shunhua , Li Fei , Zhu Xuan , Liao Wangdi
Published: August 2018

We report a case of acute myeloid leukemia with myelodysplasia-related changes in a patient with Crohn’s disease. The patient was diagnosed with Crohn’s disease at the age of 47 years and was treated with the tumor necrosis factor α inhibitors adalimumab and infliximab, and a short course of azathioprine. Four years later, the patient developed acute myeloid leukemia with myelodysplasia that involved mainly erythropoiesis. Crohn’s disease is associated with an increased risk of cancers including hematological malignancies. Cancer surveillance including hematology assessment is warranted to monitor the patients on immunosuppressive therapy.
Aromatase Inhibitor-Associated Tendinopathy and Muscle Tendon Rupture: Report of Three Cases of This Exceedingly Rare Adverse Event
Authors: Mitsimponas Nikolaos , Klouva Evangelia , Tryfonopoulos Dimitrios , Grivas Anastasios , Demiri Stamatina , Koumakis George , Gouveris Panagiotis
Published: August 2018

Aromatase inhibitors (AIs) are a commonly used antihormonal therapy in the treatment of breast cancer in postmenopausal women, specifically in the treatment of hormone receptor-positive breast cancer. AI-associated tendinopathy and muscle tendon rupture is exceedingly rare. Until now, only one case with AI-associated severe tendinopathy has been reported in the medical literature, and there are no recorded cases of AI-associated muscle tendon rapture. We report three cases of postmenopausal women with hormone receptor-positive breast cancer, who experienced tendinopathy or muscle tendon rupture under antihormonal treatment with letrozole. All of the three women were in the adjuvant setting, and the treatment of tendinopathy or tendon rupture consisted of AI discontinuation, initiation of corticosteroids, or surgical treatment. Diagnosis was made via MRI. Furthermore, in our cases, there were no signs of underlying systemic disease, there was no abnormal physical activity preceding the complaints, and there was no use of other drugs beside letrozole. AIs are one of the most commonly used drugs in antihormonal therapy for hormone receptor-positive breast cancer. In every case of a female patient with hormone receptor-positive breast cancer under treatment with AIs and arthralgia, an MRI should be performed in order to exclude the presence of tendinopathy or muscle tendon rupture.
Leukoerythroblastosis with Cytopenia as an Initial Presentation of Lung Adenocarcinoma
Authors: Kotchetkov Rouslan , El-Maraghi Robert , Narsinghani Leena
Published: August 2018

A 74-year-old male with a history of chronic lymphocytic leukemia (CLL) previously treated with fludarabine/cyclophosphamide/rituximab (FCR) 5 years ago, presented with progressive fatigue, mucocutaneous bleeding, and cytopenias (hemoglobin 51 g/L, platelets 8.0 × 109/L, lymphocytes 0.4 × 109/L). He had normal respiratory findings, and no lymphadenopathy or hepatosplenomegaly. Further workup revealed a small spiculated lung nodule and multiple sclerotic bony lesions. Due to bleeding/profound thrombocytopenia, lung biopsy was not feasible. Peripheral smear revealed leukoerythroblastosis with few nucleated red blood cells and left shift of granulocytes. Bone marrow (BM) aspirate yielded a dry tap with clusters of extrinsic atypical cells on touch preparations. BM core biopsy showed infiltration and near complete replacement by a population of highly atypical cells with surrounding fibrosis. Cells were positive for cytokeratins CK7 and CK8/18, Napsin A, and thyroid transcription factor-1, specific for a primary poorly differentiated lung adenocarcinoma. Leukoerythroblastosis in association with cytopenia often indicates a BM infiltration and warrants an early BM biopsy to rule out hematological and solid malignancies, particularly in CLL patients treated with FCR. In our case, a diagnosis of a lung adenocarcinoma was established by BM examination, the only clinically feasible diagnostic modality.
High Mobility Group Box 1 Regulates Uterine Decidualization through Bone Morphogenetic Protein 2 and Plays a Role in Kruppel-Like Factor 5-Induced Stromal Differentiation
Authors: Wang Kai , Yang Zhan-Qing , Yu Hai-Fan , Wang Yu-Si , Guo Bin , Yue Zhan-Peng
Published: August 2018

Background/Aims: High mobility group box 1 (Hmgb1) is associated with a variety of physiological processes including embryonic development, cell proliferation and differentiation, but little information is available regarding its biological role in decidualization. Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to analyze the spatiotemporal expression of Hmgb1 in mouse uterus during the pre-implantation period, and explore its function and regulatory mechanisms during uterine decidualization. Results: Hmgb1 mRNA was obviously observed in uterine epithelium on day 2 and 3 of pregnancy, but its expression was scarcely detected on day 4 of pregnancy. With the onset of embryo implantation, abundant Hmgb1 expression was noted in the subluminal stromal cells around the implanting blastocyst at implantation sites. Meanwhile, the accumulation of Hmgb1 mRNA was visualized in the decidual cells. Hmgb1 advanced the proliferation of uterine stromal cells and induced the expression of prolactin family 8, subfamily a, member 2 (Prl8a2), a reliable differentiation marker for decidualization. In uterine stromal cells, cAMP analogue 8-Br-cAMP up-regulated the expression of Hmgb1, but the up-regulation was abrogated by protein kinase A (PKA) inhibitor H89. Silencing of Hmgb1 by specific siRNA impeded the induction of 8-Br-cAMP on Prl8a2. Further analysis evidenced that Hmgb1 was a critical mediator of Kruppel-like factor 5 (Klf5) function in stromal differentiation. Knockdown of bone morphogenetic protein 2 (Bmp2) prevented the up-regulation of Prl8a2 elicited by Hmgb1 overexpression, whereas addition of exogenous recombinant Bmp2 protein (rBmp2) reversed the repression of Hmgb1 siRNA on Prl8a2 expression. Conclusion: Hmgb1 may play an important role during mouse uterine decidualization.
A Minimal lncRNA-mRNA Signature Predicts Sensitivity to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Wang Qian , Li Chunmei , Tang Peipei , Ji Runyuan , Chen Song , Wen Jian
Published: August 2018

Background/Aims: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that responds in a diverse manner to neoadjuvant chemotherapy (NAC). This study was aimed to uncover an RNA signature in TNBC patients which predicts pathological complete responses (pCR) to NAC by analyzing long noncoding RNA (lncRNA) and coding gene expression. Methods: Microarray datasets from 26 TNBC patients receiving NAC including ten patients showing pCR were obtained from the Gene Expression Omnibus database. Results: A total of 172 coding genes and 84 lncRNAs were differentially expressed between patients achieving pCR and those who did not. Filtering based on the predictive efficacy of response to NAC using receiver operator characteristic curve (ROC) and area under the curve (AUC) shortlisted 23 lncRNAs and 15 coding genes from consideration. Finally, a response score consisting of 1 lncRNA and 2 coding genes was developed: response score = 2.595*BPESC1 – 1.09*WDR72 –1.428*GADD45A – 0.731. The response score had good predictive performance (AUC=0.931, p< 0.01) and at the cut-off of 0.545, the response score had sensitivity and specificity of 0.8 and 0.9, respectively. Conclusion: We propose a simple gene expression signature of only three RNA species could be employed clinically to predict pCR in TNBC patients receiving NAC.
Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies
Authors: Müller Paula , Lemcke Heiko , David Robert
Published: August 2018

A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.
Relationship between serum thyrotropin and urine albumin excretion in euthyroid subjects with diabetes
Authors: Das Gautam , Taylor Peter N , Abusahmin Hussam , Ali Amer , Tennant Brian P , Geen John , Okosieme Onyebuchi
Published: August 2018

Background

Microalbuminuria represents vascular and endothelial dysfunction. Thyroid hormones can influence urine albumin excretion as it exerts crucial effects on the kidney and on the vascular system. This study explores the relationship between serum thyrotropin and urine albumin excretion in euthyroid patients with diabetes.

Methods

A total of 433 patients with type 1 or 2 diabetes were included in this retrospective cross-sectional study. Data included anthropometric measurements and biochemical parameters from diabetes clinic. Males with urine albumin creatinine ratio >2.5 and female’s >3.5 mg/mmoL were considered to have microalbuminuria.

Results

34.9% of the patients had microalbuminuria. Prevalence of microalbuminuria increased according to TSH quartiles (26.9, 34.6, 38.5 and 44.9%, P for trend = 0.02). In a fully adjusted logistic regression model, higher TSH concentrations were associated with high prevalence of microalbuminuria (adjusted odds ratio 2.06 [95% CI: 1.14–3.72]; P = 0.02), while comparing the highest with the lowest quartile of TSH. Multiple linear regression analysis showed an independent association between serum TSH and urine albumin creatinine ratio (β = 0.007, t = 2.03 and P = 0.04). The risk of having microalbuminuria was higher with rise in TSH concentration in patients with younger age (<65 years), raised body mass index (≥25 kg/m2), hypertension, type 2 diabetes and hyperlipidaemia and age was the most important determinant ( P for interaction = 0.02).

Conclusion

Serum TSH even in the euthyroid range was positively associated with microalbuminuria in euthyroid patients with diabetes independent of traditional risk factors. This relationship was strongest in patients with components of the metabolic syndrome.
A Compass for Navigating Sharing Economy Business Models
Authors: Muñoz Pablo , Cohen Boyd
Published: August 2018

The sharing economy has emerged in recent years as a disruptive approach to traditional business models. Drawing on a multi-year research program and a design-based methodology, this article introduces a framework and generative tool called the Sharing Business Model Compass. As an actionable framework, the Compass helps elucidate the multiple, innovative forms sharing economy businesses are adopting. As a generative tool, it enables entrepreneurs, investors, incubators, and incumbents interested in entering the sharing economy to create, present, and evolve a compelling sharing business model as well as evaluate its extent of robustness.
Working at the boundaries: Middle managerial work as a source of emancipation and alienation
Authors: Azambuja Ricardo , Islam Gazi
Published: August 2018

The current article examines the experience of middle management through the concept of boundary work, characterized as the work of negotiating between multiple roles in the interstices of organizational groups. Through an ethnographic study of a Brazilian accounting firm, we explore the ambivalent experience of boundary work as characteristic of professional middle managerial workers. Our managers described themselves as proactive and reflexive agents, on the one hand, yet also as lacking autonomy and a sense of belonging, on the other. We examine this tension as a contrast between forces of emancipation (i.e. sense of mastery, autonomy, empowerment and reflexivity) and alienation (i.e. fatigue, lack of self-determination, and detachment from their profession and coworkers). We discuss these forces and their implications for managerial work in the light that, in our findings, managers routinely shift between being agential and reflexive mediators (boundary subjects) and interfacing and coordination devices (boundary objects).
A Panel Data Analysis of Foreign Direct Investment Inflows into India Since 1991 to 2015
Authors: Javed Roohi , Javed Farheen
Published: August 2018

At the outset, this study dwells on the ambiguities surrounding the definition of foreign direct investment (FDI) and the non-adherence to international norms in measuring the FDI inflows by India. The study finds that portfolio investors and round-tripping investments have been important contributors to India’s reported FDI inflows, thus, blurring the distinction between direct and portfolio investors on the one hand and foreign and domestic investors on the other. These investors were also the ones who have exploited the tax haven route the most. These observations acquire added significance in the context of the substantial fall in the inflows seen during 1991–1992 to April 2015–December 2015.

FDI as a strategic component of investment is needed by India for achieving the economic reforms and maintaining the pace of growth and development of the economy. The government should design the FDI policy in such a way where FDI inflow can be utilised as a means of enhancing domestic production, savings and exports through the equitable distribution among states by providing much freedom to states, so that they can attract FDI inflows at their own level. The impact of FDI inflows into India in recent years is highly significant.

JEL: C40, C82, E44, F210, G15
Industrial Location Policy in India
Authors: Ramaul Nalin Kumar , Ramaul Pinki
Published: August 2018

The article provides a broad overview of the industrial location policy in India since Independence. In India, the glaring regional imbalances and inequalities have arisen through a complex set of historical, socio-economic, demographic and cultural factors. The pre-reform approach to industrial location policy involved top-down identification of lagging areas and targeting them with interventionist and regulatory measures. In the post-reform period, the process of liberalisation has curtailed the role of government as industrial owner and location regulator, and restricted policy space. Thus, the focus shifted to a targeted approach and subnational strategies. Package for industrial development are in operation for the special category states, namely northeastern states, Jammu and Kashmir (J&K), Himachal Pradesh and Uttarakhand. In other regions, the development of industries adopted a cluster development approach. However, the peripheral lagging regions continue to stagnate despite the industrial location policy having tried virtually everything. The persistently growing regional disparity in post-reform period is a matter of grave concern.

JEL Classification: R3, L5
Economies of Scale in Public Sector Banks
Authors: Bishnoi Tulchha Ram , Sh. Sofia Devi
Published: August 2018

The present study attempts to analyse the cost analysis of the banking industry with special focus on optimum size of a bank. It studies the cost structure, economies/diseconomies as well as the optimum size of public sector banks for the period 1991–1992 to 2013–2014. Economies of scale relating to 26 public sector banks are worked out for selected years. The large banks operated at a scale, reaping economies in all the years, the exception being the year 2004–2005 achieving position of the minimum AC—. For the small banks, there are economies of scale in all the selected years. Both the banks groups did not show diseconomies with respect to total cost, even though there were diseconomies associated with other individual cost items. The minimum efficient size (MES) was attained by all the public sector banks in each of the years selected.

JEL codes: D24, D210, D220, D240, D240, D250
Does Privatising the Public Interest Guarantee School Quality in India? Looking through the Lens of Teacher Education
Authors: Mythili N.
Published: August 2018

There is a monopolistic competition in teacher education (TE) at the national level, characterised by a large number of substandard private stand-alone institutions. There is oligopoly at the regional level in which few states provide TE to the entire region. This is especially true for southern and western regions. Substandard private stand-alone teachers educational institutions (TEIs) are in majority in these regions. In this way, substandard private institutions have captured the TE market. So monopolistic competition has not contributed to TE quality in India. Oligopoly has neither ensured fair distribution of teachers nor adequately addressed teachers’ deficit within the regions. National Council of Teacher Education (NCTE), as a regulatory body, has failed to control these two market behaviours due to its own inherent weaknesses such as lack of skills, bureaucratic ineptitude and lack of ability to handle the complexity of technical knowledge. All these have led to information asymmetry within NCTE and poor teacher quality. In turn, school education suffers from lower levels of student learning. So, privatising the public interest of TE does not guarantee quality. NCTE must develop a robust TE management information system to address its inherent weaknesses.
Regulating the Electoral Domain: The Election Commission of India
Authors: Singh Ujjwal Kumar , Roy Anupama
Published: August 2018

The Election Commission of India (ECI) is generally seen as a regulatory body with the power to enforce rules for the efficient conduct of elections. The ECI performs a range of overlapping functions, not all of which are regulatory. The ECI has been actively engaged in framing rules that constitute both the procedural and substantive aspects of electoral democracy in India. Following successive court decisions, Article 324 has become a ‘reservoir of powers’ giving the ECI scope for the exercise of residuary powers in a variety of situations. The ‘legal doctrine of electoral exceptionalism’ during election time has made itself manifest in the Model Code of Conduct. Innovations in ‘voter education and awareness’, which are often seen through the lens of electoral ‘management’ and the framework of ‘electoral integrity’, have become part of the deliberative content of election alongside the quest for ‘procedural certainty’ and ‘democratic outcomes’.
Damage characterization of composites to support an orthotropic plasticity material model
Authors: Khaled Bilal , Shyamsunder Loukham , Hoffarth Canio , Rajan Subramaniam D , Goldberg Robert K , Carney Kelly S , DuBois Paul , Blankenhorn Gunther
Published: August 2018

The focus of this paper is the development of test procedures to characterize the damage-related behavior of a unidirectional composite at room temperature and quasi-static loading conditions and use the resulting data in the damage sub-model of a newly developed material model for orthotropic composites. This material model has three distinct sub-models to handle elastic and inelastic deformations, damage, and failure. A unidirectional composite—T800/F3900 that was the focus of our previous work, is used to illustrate how the deformation and damage-related experimental procedures are developed and used. The implementation of the damage sub-model into LS-DYNA is verified using single-element tests and validated using impact tests. Results show that the implementation yields reasonably accurate predictions of impact behavior involving deformation and damage in structural composites.
Mechanistic model for fiber crack density prediction in cyclically loaded carbon fiber-reinforced polymer during the damage initiation phase
Authors: Hiremath Chandrashekhar P , Senthilnathan K , Naik Niranjan K , Guha Anirban , Tewari Asim
Published: August 2018

Prediction of the fiber crack density (as one of the microstructural damages) for unidirectional fiber-reinforced polymer composite under monotonic tensile load, using strength models, has been reported in the literature. However, the microstructural damage prediction for a fiber-reinforced polymer subjected to fatigue loading is still a challenge. In this work, a progressive damage initiation model was developed to predict the fiber crack density in carbon fiber-reinforced polymer composite subjected to fatigue loading. A stochastic model was used for modeling the fiber fatigue strength. Reduction in effective life of the fiber was modeled using linear Miner’s rule. Effect of fatigue strength parameters on fiber crack density was found to be considerable compared to the effect of interface shear strength. At a low number of cycles, fiber crack density obtained from the model was in good agreement with the experimentally measured fiber crack density.
A State-Wide Program for Educational Efficiency
Authors: Francis John H.
Published: August 2018

Address at Ohio State Association. From Ohio Educational Monthly.
Let Laughter In!
Authors: Nash Winifred H.
Published: August 2018

A plea for cultivation of a sense of humor as part of the course in high school English.
Brain Processing (Auditory Event-Related Potential) of Stressed Versus Unstressed Words in Thai Speech
Authors: Arunphalungsanti Kittipun , Pichitpornchai Chailerd
Published: August 2018

This study investigated the effect of the stressed word in Thai language on auditory event-related potential (aERP) in unattended conditions. We presented 30 healthy participants with monosyllabic Thai words consisting of either stressed or unstressed words. We instructed them not to attend to the sound stimuli, but rather to watch and memorize the contents of a silent natural documentary without subtitles. The two listening conditions consisted of 20% deviant stimuli (70 stressed and 70 unstressed words, respectively) and 80% standard stimuli (other 280 unstressed words) presented pseudorandomly and binaurally via a pair of earphones. Participants’ aERPs from the two conditions were evaluated by the mismatch negativity (MMN) component of aERP. The mismatch negativity amplitudes in the stressed word condition were significantly higher than those in the unstressed word condition, especially in frontal and left fronto-central brain areas. Therefore, these data show the role of the frontal and left fronto-central brain regions in auditory preattentive processing of stressed word perception among native Thai speakers. This is the first study demonstration that stressed meaningful monosyllable words in tonal language facilitate word perception in this preattentive stage. This result has implications for developing clinical tests evaluating preattentive speech perception.
Acceptance of Workplace Bullying Behaviors and Job Satisfaction: Moderated Mediation Analysis With Coping Self-Efficacy and Exposure to Bullying
Authors: Vukelić Milica , Čizmić Svetlana , Petrović Ivana B.
Published: August 2018

Previous research explored workplace climate as a factor of workplace bullying and coping with workplace bullying, but these concepts were not closely related to workplace bullying behaviors (WBBs). To examine whether the perceived exposure to bullying mediates the relationship between the climate of accepting WBBs and job satisfaction under the condition of different levels of WBBs coping self-efficacy beliefs, we performed moderated mediation analysis. The Negative Acts Questionnaire – Revised was given to 329 employees from Serbia for assessing perceived exposure to bullying. Leaving the original scale items, the instruction of the original Negative Acts Questionnaire – Revised was modified for assessing (1) the climate of accepting WBBs and (2) WBBs coping self-efficacy beliefs. There was a significant negative relationship between exposure to bullying and job satisfaction. WBB acceptance climate was positively related to exposure to workplace bullying and negatively related to job satisfaction. WBB acceptance climate had an indirect relationship with job satisfaction through bullying exposure, and the relationship between WBB acceptance and exposure to bullying was weaker among those who believed that they were more efficient in coping with workplace bullying. Workplace bullying could be sustained by WBB acceptance climate which threatens the job-related outcomes. WBBs coping self-efficacy beliefs have some buffering effects.
Unemployment Normalization: Its Effect on Mental Health During Various Stages of Unemployment
Authors: Thill Steve , Houssemand Claude , Pignault Anne
Published: August 2018

The negative effects of job loss on mental health have been thoroughly described in the literature. However, different fluctuations in mental health during the unemployment period have been noticed. We argue that a coping process takes place in this kind of situation. Therefore, in this study, we investigated the effect of the unemployment normalization process on mental health during various stages of unemployment. Participants ( N = 803) completed the General Health Questionaire-12 and the Unemployment Normalization Questionnaire. Results showed that a negative perception of unemployment had the greatest impact on mental health during the different phases of unemployment. Nevertheless, during the first year, having a positive perception counteracted these negative effects, and after 1 year, the unemployment norm took over the role of buffering against the negative effects on mental health. These results indicate that unemployment is still perceived as negative, but depending on the stage of unemployment, various coping strategies are used to buffer the negative consequences of unemployment.
Adherence to health management guidelines for children with Down’s syndrome at the Bustamante Hospital for Children, Jamaica
Authors: Livingstone-Sinclair Keisha , Scott Charmaine , Trotman Helen
Published: August 2018

Health surveillance of children with Down’s syndrome may be inadequate. We aimed to assess adherence to health management guidelines at the main paediatric hospital in Jamaica. Ours was a retrospective descriptive study over a five-year period. Data on demographics, co-morbidities, investigations, referrals and interventions were recorded. Of 41 children included in the study, 85% were diagnosed in the neonatal period. Congenital heart disease in 29 (76%) and ophthalmological disorders in 13/24 (54%) were the most common co-morbidities. Evaluations in accordance with the American Academy of Pediatrics guidelines were carried out in only 46% of the children for echocardiography, 48% for ophthalmology, 30% for hearing evaluation and 10% for neonatal thyroid screening. Thus, the recommended guidelines were not carried out in a timely manner in the majority of the children. Education of healthcare providers and caregivers along with the provision of adequate resources may help to resolve this inadequacy.
Tuberculosis of the thyroid in Togo: a clinicopathologic study of 11 presumed cases
Authors: Darre Tchin , Amana Bathokédeou , Pegbessou Essobozou , Winga Foma , Warou Dolou , Napo-Koura Gado
Published: August 2018

Tuberculosis (TB) remains a real public health concern in Africa; thyroid localisation of the disease is a very rare form of extrapulmonary TB. We conducted a descriptive and cross-sectional study on all histologically proved cases of thyroid TB diagnosed in Togo over the last 20 years. Eleven cases of TB of the thyroid were identified, of which nine were in women, with an average age of 29.4 ± 0.2 years. The clinical signs were the presence of a nodule in seven, an abscess in three and a swelling with cutaneous fistulisation in one. Thyroid involvement alone was found in four, associated with pleuropulmonary TB in six and mammary TB in one. Human immunodeficiency virus (HIV) co-infection was present in six. All histopathology results showed inflammatory granulomata with caseous necrosis. The clinical features are often misleading and pose a real diagnostic problem, especially with differentials of simple abscess and cancer.
Impaired cerebral autoregulation and neurovascular coupling in middle cerebral artery stroke: Influence of severity?
Authors: Salinet Angela SM , Silva Nathália CC , Caldas Juliana , de Azevedo Daniel S , de-Lima-Oliveira Marcelo , Nogueira Ricardo C , Conforto Adriana B , Texeira Manoel J , Robinson Thompson G , Panerai Ronney B , Bor-Seng-Shu Edson
Published: August 2018

We aimed to assess cerebral autoregulation (CA) and neurovascular coupling (NVC) in stroke patients of differing severity comparing responses to healthy controls and explore the association between CA and NVC with functional outcome. Patients admitted with middle cerebral artery (MCA) stroke and healthy controls were recruited. Stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS) scores: ≤4 mild, 5–15 moderate and ≥16 severe. Transcranial Doppler ultrasound and Finometer recorded MCA cerebral blood flow velocity (CBFv) and blood pressure, respectively, over 5 min baseline and 1 min passive movement of the elbow to calculate the autoregulation index (ARI) and CBFv amplitude responses to movement. All participants were followed up for three months. A total of 87 participants enrolled in the study, including 15 mild, 27 moderate and 13 severe stroke patients, and 32 control subjects. ARI was lower in the affected hemisphere (AH) of moderate and severe stroke groups. Decreased NVC was seen bilaterally in all stroke groups. CA and NVC correlated with stroke severity and functional outcome. CBFv regulation is significantly impaired in acute stroke, and further compromised with increasing stroke severity. Preserved CA and NVC in the acute period were associated with improved three-month functional outcome.
Cancer precision medicine today: Towards omic information in healthcare systems
Authors: Maggi Norbert , Gazzarata Roberta , Ruggiero Carmelina , Lombardo Claudio , Giacomini Mauro
Published: August 2018

Introduction:

This article focuses on the integration of omics data in electronic health records and on interoperability aspects relating to big data analysis for precision medicine.

Methods:

Omics data integration methods for electronic health record and for systems interoperability are considered, with special reference to the high number of specific software tools used to manage different aspects of patient treatment. This is an important barrier against the use of this integrated approach in daily clinical routine.

Results:

The correct use of all three levels of interoperability (technical, semantic, and process interoperability) plays a key role in order to achieve an easy access to a significant amount of data, all with correct contextualization, which is the only way to obtain a real value from data for precision medicine.

Conclusions:

The proposed architecture could improve the potentialities of data routinely collected in many health information systems to form a real patient center information environment.