bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and Role of hERG1 Channels in Pediatric Acute Lymphoblastic Leukemias: Shortcoming of Drug Resistance by hERG1 Channel Inhibitors in Stoma-Supported Leukaemia Cell Cultures In Vitro.
Authors: Pillozzi Serena , Accordi Benedetta , Veltroni Marinella , Masselli Marika , Pancrazzi Elisa , Gaipa Giuseppe , Lippi Alma , Bernini Gabriella , Basso Giuseppe , Arcangeli Annarosa
Published: November 2019

Therapy resistance is still a major obstacle to successful treatment in a significant number of pediatric acute lymphoblastic leukaemia (ALL) patients. It has been previously demonstrated that children with ALL whose leukemia cells exhibit in vitro resistance to single or a combination of drugs have a significantly worse prognosis compared to patients with sensitive leukemic cells (Ramakers-van Woerden N, et al Leukemia18(3):521–9 2004). Ion channels are becoming one of the potential targets for cancer therapy and putative biochemical modulators of conventional chemotherapy (Conti M, J Exp Ther Oncol. 4(2):161–6, 2004). In particular, K+ channels belonging to the hERG1 family are attracting most attention, since they are over-expressed in a broad range of primary acute myeloid leukaemias (AML) as well as in both myeloid and lymphoid leukemic cell lines (Pillozzi S, et al Leukemia16:1791–1798, 2002; Smith GA, et al, JBC227:18528–18534, 2002). hERG1 channel expression confers a greater capacity to engraft the bone marrow and invade the bloodstream in NOD/SCID mice injected with AML cells. This fact corresponds to a greater malignancy (shorter overall survival and higher probability to relapse) in hERG1 positive AML patients (Pillozzi S, et al Blood110:1238–1250, 2007). It was also recently shown that the expression of hERG1 is related to the chemosensitivity of cancer cells to vincristine, paclitaxel, and hydroxy-camptothecin (Chen SZ, et al Cancer Chemother Pharmacol56(2):212–20, 2005). We studied the expression and role of hERG1 channels in various B lymphoid leukaemia cell lines and primary childhood B lymphoid leukaemia samples. It emerged that:

hERG1 K+ channels are expressed in both all the leukaemia cell lines and primary childhood B leukaemia samples; the N-terminus deleted, herg1b isoform was preferentially expressed in both cell lines and primary samples; in childhood leukaemia patients, the level of herg1b expression correlated with response to therapy.

B lymphoid leukaemia cell lines were co-cultured on human bone marrow stromal cells, a system known to enhance leukaemia cell survival and escape from drug-induced apoptosis. In these cultures, the addition of a specific hERG1 inhibitor, E4031, induced a significant apoptosis in leukaemia cells, bypassing the protective effect of the bone marrow microenvironment. We hypothesise that hERG1 channels can represent a novel molecular device regulating drug sensitivity in childhood acute leukaemia cells, and that targeting of hERG1 channels can restore a proper pro-apoptotic response to chemotherapy in resistant B lymphoid leukemic cells.
Targeting An Ancient Retrovirus In Tumor Using Engineered T Cells
Authors: Krishnamurthy Janani , Rabinovich Brian , Olivares Simon , Teijuan Mi , Switzer Kirsten , Plummer Joshua , Maiti Sourindra , Singh Harjeet , Huls Helen , Johanning Feng-wang , Cooper Laurence J N
Published: November 2019

Human endogenous retroviruses (HERVs) are ancient viruses forming 8% of human genome. One subset of HERVs, the HERV-K has recently been found to be expressed on tumor cells including melanoma, breast cancer and lymphoma but not on normal body cells. Thus, targeting HERV-K protein as a tumor associated antigen (TAA) may be a potential treatment strategy for tumors that are resistant to conventional therapies. One approach to improve therapeutic outcome is by infusing T cells rendered specific for such TAAs preferentially expressed on tumor cells. Recognition of cell-surface TAAs independent of major histocompatibility complex can be achieved by introducing a chimeric antigen receptor (CAR) on T cells using gene therapy. This approach is currently being used in our clinical trials adoptively transferring CD19-specific CAR+ T cells into patients with B-lineage malignancies. Preliminary analysis of HERV-K env protein expression in 268 melanoma samples and 139 normal organ donor tissues using immunohistochemistry demonstrated antigen expression in tumor cells and absence of expression in normal organ tissues. The scFv region from a mouse monoclonal antibody to target HERV-K env was used to generate a CAR and cloned into Sleeping Beauty (SB) plasmid for stable expression in T cells. HERV-K-specific CAR+T cells were selectively propagated ex vivo on artificial antigen presenting cells (aAPC) using an approach already in our clinical trials. Indeed, after genetic modification of T cells and selection on HERV-K+ aAPC, over 95% of propagated T cells stably expressed the introduced HERV-K-specific CAR and exhibited redirected specificity for HERV-K+ melanoma (Figure 1). Further, the adoptive transfer of HERV-K-specific CAR+T cells killed metastatic melanoma in a mouse xenograph model. While we have chosen melanoma as our tumor model, this study has the potential to be applied to other malignancies, including lymphoma and myeloma due to restricted expression of HERV-K envelope (env) protein on these tumor cells. These data demonstrate that it is feasible to generate T cells expressing a HERV-K-specific CAR using a clinically-appealing approach as a treatment strategy for HERV-K env+ tumors.

Disclosures:

No relevant conflicts of interest to declare.
Fibrin formation, fibrinopeptide A release, and platelet thrombus dimensions on subendothelium exposed to flowing native blood: greater in factor XII and XI than in factor VIII and IX deficiency
Authors: Weiss HJ , Turitto VT , Vicic WJ , Baumgartner HR
Published: November 2019

Fibrin deposition and platelet thrombus dimensions on subendothelium were studied in four groups of patients with coagulation factor deficiencies. Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe bleeders, whereas four patients with factor XII deficiency and seven with factor XI deficiency were either asymptomatic or only mild bleeders despite APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted segments of deendothelialized rabbit aorta were exposed at a shear rate of 650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular chamber. Blood coagulation was evaluated by measuring fibrin deposition (percent surface coverage) on the subendothelium and post-chamber fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium were evaluated by determining the total thrombus volume per surface area (using an optical scanning technique) and the average height of the three tallest thrombi. Consistent differences were observed among the patient groups for both the 5-min and 10-min exposure times. The larger of the 5- and 10-min exposure-time values was used to calculate group averages. Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and post- chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly decreased fibrin deposition and fibrinopeptide A levels were observed in factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly higher values were obtained in patients deficient in factor XI (33% +/- 5% and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml). Differences in thrombus dimensions were also observed. In normal subjects, the value for thrombus volume and average height of the tallest thrombi were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively, and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5 +/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/- 3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient with fibrinogen deficiency, indicating that the smaller thrombi in factor VIII and factor IX deficiencies were probably due to impaired evolution of thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400 WORDS)
A case of dyskinesia after levetiracetam administration
Authors: Yim Soo Hwan , Choi Yun Ho , Heo Kyoung , Cho Kyoo ho
Published: November 2019

Background

Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported.

Case presentation

A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs.

Discussion and conclusions

To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.
Searching for optimal blood pressure targets in type 2 diabetic patients with coronary artery disease
Authors: Shen Ying , Dai Yang , Wang Xiao Qun , Zhang Rui Yan , Lu Lin , Ding Feng Hua , Shen Wei Feng
Published: November 2019

Background

Controversies exist regarding the optimal blood pressure (BP) level that is safe and provides cardiovascular protection in patients with type 2 diabetes mellitus (T2DM) and coexistent coronary artery disease. Several new glucose-lowering agents have been found to lower BP as well, making the interaction between BP and T2DM even more complex.

Methods

With the reference to recent literature, this review article describes the potential mechanisms of increased risk of hypertension in T2DM and outlines the possible optimal BP levels based upon recommendations on the management of hypertension by the current guidelines, in combination with our research findings, for type 2 diabetic patients with coronary artery disease.

Results

The development of hypertension in T2DM involves multiple processes, including enhanced sympathetic output, inappropriate activation of renin-angiotensin- aldosterone system, endothelial dysfunction induced through insulin resistance, and abnormal sodium handling by the kidney. Both AGE-RAGE axis and adipokine dysregulation activate intracellular signaling pathways, increase oxidative stress, and aggravate vascular inflammation. Pancreatic β-cell specific microRNAs are implicated in gene expression and diabetic complications. Non-pharmacological intervention with lifestyle changes improves BP control, and anti-hypertensive medications with ACEI/ARB, calcium antagonists, β-blockers, diuretics and new hypoglycemic agent SGLT2 inhibitors are effective to decrease mortality and prevent major adverse cardiovascular events. For hypertensive patients with T2DM and stable coronary artery disease, control of BP < 130/80 mmHg but not < 120/70 mmHg is reasonable, whereas for those with chronic total occlusion or acute coronary syndromes, an ideal BP target may be somewhat higher (< 140/90 mmHg). Caution is advised with aggressive lowering of diastolic BP to a critical threshold (< 60 mmHg).

Conclusions

Hypertension and T2DM share certain similar aspects of pathophysiology, and BP control should be individualized to minimize adverse events and maximize benefits especially for patients with T2DM and coronary artery disease.
LncRNA SNHG8 is identified as a key regulator of acute myocardial infarction by RNA-seq analysis
Authors: Zhuo Liu-An , Wen Yi-Tao , Wang Yong , Liang Zhi-Fang , Wu Gang , Nong Mei-Dan , Miao Liu
Published: November 2019

Background

Long noncoding RNAs (lncRNAs) are involved in numerous physiological functions. However, their mechanisms in acute myocardial infarction (AMI) are not well understood.

Methods

We performed an RNA-seq analysis to explore the molecular mechanism of AMI by constructing a lncRNA-miRNA-mRNA axis based on the ceRNA hypothesis. The target microRNA data were used to design a global AMI triple network. Thereafter, a functional enrichment analysis and clustering topological analyses were conducted by using the triple network. The expression of lncRNA SNHG8, SOCS3 and ICAM1 was measured by qRT-PCR. The prognostic values of lncRNA SNHG8, SOCS3 and ICAM1 were evaluated using a receiver operating characteristic (ROC) curve.

Results

An AMI lncRNA-miRNA-mRNA network was constructed that included two mRNAs, one miRNA and one lncRNA. After RT-PCR validation of lncRNA SNHG8, SOCS3 and ICAM1 between the AMI and normal samples, only lncRNA SNHG8 had significant diagnostic value for further analysis. The ROC curve showed that SNHG8 presented an AUC of 0.850, while the AUC of SOCS3 was 0.633 and that of ICAM1 was 0.594. After a pairwise comparison, we found that SNHG8 was statistically significant (PSNHG8-ICAM1 = 0.002; PSNHG8-SOCS3 = 0.031). The results of a functional enrichment analysis of the interacting genes and microRNAs showed that the shared lncRNA SNHG8 may be a new factor in AMI.

Conclusions

Our investigation of the lncRNA-miRNA-mRNA regulatory networks in AMI revealed a novel lncRNA, lncRNA SNHG8, as a risk factor for AMI and expanded our understanding of the mechanisms involved in the pathogenesis of AMI.
Bee pollen and propolis improve neuroinflammation and dysbiosis induced by propionic acid, a short chain fatty acid in a rodent model of autism
Authors: Aabed Kawther , Bhat Ramesa Shafi , Al-Dbass Abeer , Moubayed Nadine , Algahtani Norah , Merghani Nada M. , Alanazi Azizah , Zayed Naima , El-Ansary Afaf
Published: November 2019

Background

Neuroinflammation plays a major role in the pathogenesis of autism because the cytokine levels are typically disturbed in the brain in autistic patients. Prebiotics-rich diet maintains the healthy gut microbiota and hence can regulate the neuroinflammation indirectly. The study aimed to investigate the role of bee pollen and propolis in ameliorating neuroinflammation, including cytokine levels, in an animal model of autism.

Methods

Hamsters were classified as four groups: Group I, control; Group II, autistic model/animals treated with 250 mg propionic acid (PPA)/kg body weight (BW)/day for 3 days; Group III, animals treated with bee pollen at a dose of 250 mg/kg BW/day for 4 weeks; and Group IV, animals treated with propolis at a dose of 250 mg/kg BW/day for 4 weeks. Neuroinflammatory responses were evaluated using the levels of interferon γ (IFN-γ), interleukin 1 alpha (IL-1α), IL-6, IL-10, IL-12 (p70), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNFα).

Results

Significant decrease of IL-10 (P<0.026), VEGF (P<0.005), and TNFα(P<0.005) levels and increased IL-1α (P<0.032), IL-6(P<0.028), and IFN-γ (P<0.013) levels were observed between the four studied groups. The neurotoxic effects of PPA was clearly presented as much higher IL-6, as pro-inflammatory cytokine (P<0.05), concomitant with much lower IL-10, as anti-inflammatory cytokine(P<0.015) compared to controls. Both bee pollen and propolis were effective in ameliorating the neurotoxic effects of PPA demonstrating non-significant changes of IL-6 and IL-10 when compared to control healthy hamsters.

Conclusions

Our findings indicate that both bee pollen and propolis protect against neuroinflammation in the rodent model of autism. However, further studies are needed to investigate the clinical benefits of prebiotics-rich diet in neurodevelopmental disorders, such as autism.
Cervical invasion, lymphovascular space invasion, and ovarian metastasis as predictors of lymph node metastasis and poor outcome on stages I to III endometrial cancers: a single-center retrospective study
Authors: Li Min , Wu Shuwei , Xie Yangqin , Zhang Xiaohui , Wang Zhanyu , Zhu Ying , Yan Shijie
Published: November 2019

Background

The aim of this study is to determine pathological factors that increase the risk of LNM and indicate poor survival of patients diagnosed with endometrial cancer and treated with surgical staging.

Method

Between January 2010 and November 2018, we enrolled 874 eligible patients who received staging surgery in the First Affiliated Hospital of Anhui Medical University. The roles of prognostic risk factors, such as age, histological subtype, tumor grade, myometrial infiltration, tumor diameter, cervical infiltration, lymphopoiesis space invasion (LVSI), CA125, and ascites, were evaluated. Multivariable logistic regression models were used to identify the predictors of LNM. Kaplan–Meier and COX regression models were utilized to study the overall survival.

Results

Multivariable regression analysis confirmed cervical stromal invasion (OR 3.412, 95% CI 1.631–7.141; P < 0.01), LVSI (OR 2.542, 95% CI 1.061–6.004; P = 0.04) and ovarian metastasis (OR 6.236, 95% CI 1.561–24.904; P = 0.01) as significant predictors of nodal dissemination. Furthermore, pathological pattern (P = 0.03), myometrial invasion (OR 2.70, 95% CI 1.139–6.40; P = 0.01), and lymph node metastasis (OR 9.675, 95% CI 3.708–25.245; P < 0.01) were independent predictors of decreased overall survival.

Conclusions

Cervical invasion, lymphopoiesis space invasion, and ovarian metastasis significantly convey the risk of LNM. Pathological type, myometrial invasion, and lymph node metastasis are all important predictors of survival and should be scheduled for completion when possible in the surgical staging procedure.
Correction to: Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity
Authors: Chen Ching-Yi , Liao Po-Lin , Tsai Chi-Hao , Chan Yen-Ju , Cheng Yu-Wen , Hwang Ling-Ling , Lin Kuan-Hung , Yen Ting-Ling , Li Ching-Hao
Published: November 2019

It was highlighted that the original article [1] contained the wrong Fig. 1.
Assessment of computational methods for the analysis of single-cell ATAC-seq data
Authors: Chen Huidong , Lareau Caleb , Andreani Tommaso , Vinyard Michael E. , Garcia Sara P. , Clement Kendell , Andrade-Navarro Miguel A. , Buenrostro Jason D. , Pinello Luca
Published: November 2019

Background

Recent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysis presents unique methodological challenges. scATAC-seq experiments sample DNA, which, due to low copy numbers (diploid in humans), lead to inherent data sparsity (1–10% of peaks detected per cell) compared to transcriptomic (scRNA-seq) data (10–45% of expressed genes detected per cell). Such challenges in data generation emphasize the need for informative features to assess cell heterogeneity at the chromatin level.

Results

We present a benchmarking framework that is applied to 10 computational methods for scATAC-seq on 13 synthetic and real datasets from different assays, profiling cell types from diverse tissues and organisms. Methods for processing and featurizing scATAC-seq data were compared by their ability to discriminate cell types when combined with common unsupervised clustering approaches. We rank evaluated methods and discuss computational challenges associated with scATAC-seq analysis including inherently sparse data, determination of features, peak calling, the effects of sequencing coverage and noise, and clustering performance. Running times and memory requirements are also discussed.

Conclusions

This reference summary of scATAC-seq methods offers recommendations for best practices with consideration for both the non-expert user and the methods developer. Despite variation across methods and datasets, SnapATAC, Cusanovich2018, and cisTopic outperform other methods in separating cell populations of different coverages and noise levels in both synthetic and real datasets. Notably, SnapATAC is the only method able to analyze a large dataset (> 80,000 cells).
Canine cutaneous and renal glomerular vasculopathy in the Republic of Ireland: a description of three cases
Authors: Hope Aimee , Martinez Carlos , Cassidy Joseph P. , Gallagher Barbara , Mooney Carmel T.
Published: November 2019

Background

Cutaneous and renal glomerular vasculopathy (CRGV) is a condition of unknown aetiology involving microvascular thrombosis. It has recently been described in over 160 dogs in the United Kingdom and usually has a grave prognosis. To date, this condition has not been described in dogs residing in the Republic of Ireland.

Case presentation

Three dogs presented to University College Dublin Veterinary Hospital (UCDVH) for investigation of rapidly progressive skin lesions. All dogs were diagnosed with CRGV on post-mortem examination. All three dogs had azotaemia on presentation or rapidly developed azotaemia, and all were euthanased because of progression of clinical signs and likelihood of CRGV. One dog was affected by seizure-like episodes and had thrombotic microangiopathy evident within the cerebrum.

Conclusions

CRGV occurs in dogs residing in the Republic of Ireland and is a differential for cases presenting with skin lesions and azotaemia. The histopathological lesions of CRGV can also affect the brain leading to neurological signs such as seizures. Owners and veterinarians should be aware that this condition can occur in dogs in Ireland.
Imbalance in glycemic control between the treatment and placebo groups in cardiovascular outcome trials in type 2 diabetes
Authors: Shimazawa Rumiko , Ikeda Masayuki
Published: November 2019

Background

Glycated hemoglobin (HbA1c) is accepted as the most reliable marker for assessing chronic glycemia. The present study aimed to investigate glycemic control in cardiovascular outcome trials (CVOTs) performed by pharmaceutical sponsors, at the request of the United States Food and Drug Administration (FDA) to ensure that newer hypoglycemic agents do not increase cardiovascular risk for patients with type 2 diabetes.

Methods

We chose ClinicalTrials.gov as a data source to identify randomized, double-blind, placebo-controlled non-inferiority trials of newer hypoglycemic agents for which the FDA 2008 guidance required a CVOT involving patients with type 2 diabetes.

Results

We identified 12 CVOTs, all of which were performed in accordance with the FDA guidance and published as of December 2018. Participants received either active treatment or placebo in addition to their existing therapy. On the assumption that HbA1c concentrations would be higher in the placebo group than in the treatment group, the use of open-label glucose lowering agents was encouraged as required to help all patients reach appropriate HbA1c targets according to local guidelines. As a result, the number of patients who received additional hypoglycemic agents during the trial was greater in the placebo group than in the treatment group in 10 of the CVOTs. Although the CVOTs were designed to avoid any imbalance in glycemic control between the groups, HbA1c concentrations were substantially higher in the placebo group than in the treatment group in all CVOTs throughout the observational period. The inferior glycemic control in the placebo groups was not considered in analyzing the outcomes in any of the CVOTs.

Conclusions

The safety and efficacy of new hypoglycemic agents are potentially inflated because the participants in the placebo groups unexpectedly exhibited inferior glycemic control throughout the trial compared with the outcomes in the treatment groups. This imbalance may distort data interpretation and mask potential risks of the drugs. Re-analysis with adjustment for HbA1c concentrations would determine whether the results of these CVOTs were biased by the difference in glycemic control between the treatment and placebo groups and reveal potential effects of the test drugs independent of glycemic control.
Harvesting of forest products and implications for Afrotemperate bird communities in a montane forest of the Eastern Cape, South Africa
Authors: Leaver Jessica , Carstens Johann C. , Cherry Michael I.
Published: November 2019

Background

Harvesting of forest products is a widespread driver of disturbance in developing nations, where policies are increasingly aimed at managing natural forests for sustainable use. There is thus need for research aimed at understanding the impact of resource use on forest habitats and concomitant effects on biodiversity. Afromontane forests in the Eastern Cape, South Africa are harvested informally for poles and medicinal bark and occur along elevational gradients of 800–1600 m above sea level. Patterns of spatial diversity and human disturbance are expected to be affected by elevation. Furthermore, species’ responses to disturbance are expected to vary depending on their level of habitat specialisation. Understanding harvest impacts on forest biodiversity thus requires disentangling the separate effects of elevation and disturbance, and considering forest-specialist and forest-generalist species separately. This study comprises two components. First, harvest activities, resultant harvest-mediated habitat heterogeneity, and avifaunal species richness, composition and beta-diversity were compared across two elevational zones in a harvested forest. Second, the role of harvest-mediated habitat heterogeneity in driving patterns of avifaunal diversity were assessed, while controlling for elevation, and considering forest-specialist and forest-generalist species separately.

Results

Harvest rates were higher, and activities more varied in the lower elevation zone, with significant impacts of harvesting on habitat features resulting in higher harvest-mediated habitat heterogeneity at lower elevations. Harvest-mediated increases in habitat heterogeneity positively affected forest-generalist species richness, while forest-specialist richness was negatively affected. While species composition of both groups differed across elevational zones, variation in harvest-mediated habitat heterogeneity did not fully account for this, suggesting that factors other than disturbance shape avifaunal communities along the elevation gradient. However, variation in harvest-mediated habitat heterogeneity accounted for the amount of beta-diversity attributed to species turnover in the forest-specialist assemblage, indicating that harvest disturbances affect the mechanisms driving beta-diversity of this group.

Conclusion

Spatial patterns of avifaunal diversity are affected by elevation over a 300-m gradient. Harvesting results in increased habitat heterogeneity, which variably affects avifaunal communities at the forest-scale, with positive effects for forest generalists and negative effects for forest-specialists.
Heterozygous Mutation (Q459R) in the Calcium-Sensing Receptor Gene Causes Familial Hypocalciuric Hypercalcemia 1 (FHH1)
Authors: Boisen Ida Marie , Mos Iris , Lerche-Black Eva Merete , Juul Anders , Bräuner-Osborne Hans , Blomberg Jensen Martin
Published: November 2019

Context

Several heterozygous loss-of-function mutations in the calcium-sensing receptor gene (CASR) leading to elevated ionized serum calcium and familial hypocalciuric hypercalcemia 1 (FHH1) have been characterized. Few mutations are not pathogenic, and previous studies suggested that the Q459R mutation does not result in an FHH1 phenotype.

Objective

We identified a family with a heterozygous CASR Q459R mutation and characterized their calcium homeostasis and the pathophysiological mechanisms of a homozygous and heterozygous Q459R mutation in vitro.

Design

The index patient and her family had clinical, biochemical, and genetic analyses performed. In vitro functional characterization of homozygous and heterozygous (Q459R) mutations was conducted by determining CaSR cell-surface expression and inositol monophosphate (IP1) signaling in transiently transfected human embryonic kidney 293A (HEK293A) cells.

Results

All 3 heterozygous carriers had mild asymptomatic hypercalcemia, hypocalciuria, and 2 had elevated serum parathyroid hormone (PTH). In vitro characterization in HEK293A cells revealed that CASR Q459R is a loss-of-function mutation with no impact on cell-surface expression. Cells with the homozygous Q459R genotype had significantly reduced calcium potency of IP1 signaling compared to wild type, whereas the heterozygous Q459R also had lower calcium potency albeit not significantly different from wild type.

Conclusion

A loss-of-function Q459R mutation in CASR in a family caused FHH1 characterized by elevated ionized calcium and PTH and low calcium excretion. The marked presence of CaSR at the membrane and inhibition of IP1 signaling in vitro suggest that calcimimetics may be functional in patients with this mutation, which seems to be a mild loss-of-function mutation associated with autosomal dominant transmission of FHH1.
Zhang Nuanxin and Social Commitment in 1980s Chinese Women’s Experimental Cinema
Authors: Wang Lingzhen
Published: November 2019

In December 1978, the Chinese government formally laid out its economic reform policy, thereby marking the beginning of a new post-Mao era. As economic reform deepened around the mid-1980s, the state began to openly retreat from its former socialist commitments—including the institutionalized practice of class and gender equality—and new mainstream discourses began to endorse a universal modernity, disregarding sociopolitical consequences of the market. Zhang Nuanxin (张暖忻, 1941–95) emerged as a pioneer in both the theory and practice of early post-Mao new experimental cinema, but she was dismissed as nonessential to the advancement of post-Mao new cinema in the late 1980s. Post-Mao feminist film scholars have since expressed their disappointment with Zhang’s films due to their incomplete break from the socialist mainstream cinema of the Mao era. This article closely studies Zhang’s most representative film, Sacrificed Youth (青春祭, 1985), exploring its complicated negotiation with the socialist legacy and new post-Mao discourses. With a highly subjective and documentary experimental style, the film articulates a double critique of political and cultural uniformity during the Cultural Revolution (1966–76) and the socially detached and universal individualism, naturalized sexual difference, and essentialized female consciousness newly mainstreamed around the mid-1980s in China. The article argues that the dismissal of Zhang toward the end of the 1980s reveals both the transformation of Chinese culture into a depoliticized and male-centered masculine practice and Zhang’s insistence on sociopolitically engaged filmmaking as China moved toward a market economy.
Whatever Happened to Janet Wood? Women Story Editors in 1950s Television
Authors: Berke Annie
Published: November 2019

This article places 1950s women story editors in television in the context of the studio system and explains the particular labor of the story and script editors in film and TV. It examines the extant records and archival sources (including newspapers, industry trade publications, and internal memos) of women story editors such as Dorothy Hechtlinger, Alice Young, Jacqueline Babbin, and Janet Wood in conjunction with the historical work of David Waterman and Erin Hill, as well as the theoretical model Michel Foucault posits in his essay on the criminal notices of obscure “infamous men.” These “infamous” (or, more appropriately, un-famous) women story editors become visible as they are being penalized, disciplined, or fired—which is to say, they only appear in the historical record when they are being pushed out or when they push back. As Hechtlinger writes in an angry memo to a supervisor at The United States Steel Hour (ABC, 1953–55; CBS, 1955–63), “I think it was a shameful omission that I was not permitted to attend today’s meeting.” For decades, women like Hechtlinger and Wood have suffered such “omissions” within television history. This essay seeks to integrate their stories, work, and subjectivities into the field of postwar media industry studies while revealing how this hidden history invites a rereading of media texts from the period.
Single cell transcriptome dynamics from pluripotency to FLK1+ mesoderm
Authors: Zhao Haiyong , Choi Kyunghee
Published: November 2019

Hemangiogenic progenitors generating blood and endothelial cells are specified from FLK1-expressing (FLK1+) mesoderm by the transcription factor ETV2. FLK1+ mesoderm also contributes to smooth muscle and cardiomyocytes. However, the developmental process of FLK1+ mesoderm generation and its allocation to various cell fates remain obscure. Recent single cell RNA-sequencing studies of early embryos or in vitro-differentiated human embryonic stem (ES) cells have provided unprecedented information on the spatiotemporal resolution of cells in embryogenesis. These snapshots, however, lack information on continuous dynamic developmental processes. Here, we performed single cell RNA sequencing of in vitro-differentiated mouse ES cells to capture the continuous developmental process leading to hemangiogenesis. We found that hemangiogenic progenitors from ES cells develop through intermediate gastrulation stages, which are gradually specified by ‘relay’-like highly overlapping transcription factor modules. Moreover, the transcriptional program of the Flk1+ mesoderm was maintained in the smooth muscle lineage, suggesting that smooth muscle is the default fate of Flk1+ mesoderm. We also identified the SRC kinase contributing to ETV2-mediated activation of the hemangiogenic program. This continuous transcriptome map will facilitate both basic and applied studies of mesoderm development.
Hemangioma: Recent Advances
Authors: DeHart Austin , Richter Gresham
Published: November 2019

Hemangiomas are common benign vascular tumors that often present in childhood. Diagnosis is based on clinical history, physical examination, and, when unclear, assisted with ultrasound or MRI. While the majority are small, nonproblematic, and can be managed conservatively, some hemangiomas may be associated with underlying syndromes or concerning for visceral involvement. Symptomatic lesions may develop ulceration, bleeding, vision disturbances, functional limitations, or disfigurement. The ideal treatment for a symptomatic hemangioma is often multimodal and may vary depending on the size, location, and proximity to critical structures. Medical treatments include topical beta blockers, oral propranolol, or steroid injections. Surgical resection and laser therapies may be necessary to optimize long term outcomes.
New view on alcoholic liver disease - potential role of PD1/PDL-1 pathway in the disease pathogenesis
Authors: Adamczyk Katarzyna , Kasztelan-Szczerbińska Beata , Rycyk Anna , Cichoż-Lach Halina
Published: November 2019

Introduction: Exposure to chronic, excessive alcohol consumption, its breakdown metabolites, and gut-derived endotoxins dysregulate immune signaling leading to activation of inflammation. As a result, the non-resolving inflammatory response and development of alcoholic liver disease (ALD) may occur. There are still no pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Material and Methods: The information provided was collected as a result of various article’s analyses on the development, diagnosis, and treatment of patients with alcoholic liver disease using Google Scholar and PubMed databases. Results: The pathway consisting of the programmed cell death 1 (PD-1) receptor and its ligand PD-L1 may play a critical role in the inhibition of self-reactive and inflammatory effector cells and the protection against immune-mediated tissue damage. There is a possibility of the potential gender-related differences in PD1/PD-L1 signaling in ALD. Conclusion: The better understanding of ALD as a dynamic process and all aspects of immune dysregulation may be important for the development of novel therapies in alcoholic liver disease. Results from a further study on the PD1/PDL-1 pathway might be exploited to re-define therapeutic targets and create sex-tailored treatments according to individual patient needs.
CLARICE EM CORDEL: UMA EXPERIÊNCIA LITERÁRIA NO ENSINO MÉDIO
Authors: SOARES MICHELLY CRISTINY
Published: November 2019

RESUMO: O presente trabalho, objetivou aplicar oficinas de prática de leitura a partir do conto Bonecos de Barro reescrito em cordel. Pesquisa-ação de abordagem qualitativa foi realizada, em uma turma de Ensino Médio, por meio de uma metodologia de produção textual que valoriza a cultura local. Tal estudo busca apresentar as diferenças e similaridades das estruturas do cânone e da literatura popular de cordéis e ressignificar nossa prática educativa. A fundamentação apresentada apoia-se em reflexões de concepções de Thiolent (1992), (COSSON, 2017), Lispector (1999), Leffa (1996), Todorov (2009), Solé (2009). A pesquisa permitiu compreender que a compreensão de um texto é um trabalho árduo e contínuo que se for mediado pelo professor com responsabilidade e compromisso pode gerar bons textos, como o cordel produzido, em conjunto, neste trabalho.Palavras-chave: Clarice Lispector, Cânone e Popular, Professor mediador, Conto, Cordel.
ESPAÇOS LITERÁRIOS DE DESTRUIÇÃO
Authors: GARBO KAREN CRISTINA
Published: November 2019

A emergência do conceito de destruição para pensar na literatura como espaço de novas significações, dentro da ótica deleuziana. Assim, a destruição emerge como um novo conceito dentro no contexto do capitalismo tardio, em que o colapso da história em consequência do tempo acelerado provoca novas interpretações espaciais, sobretudo na literatura. Segue a isso a análise de três obras literárias que trazem o exercício da destruição enquanto potência na literatura: 120 dias de Sodoma, de Marquês de Sade, a Colônia Penal, de Franz Kafka e a Anéis de Saturno, de W.G. Sebald.
O ROMANCE MODERNO E OS DESLOCAMENTOS DA VOZ NARRADORA: ORALIDADE E INTERSEÇÕES CULTURAIS
Authors: Azevedo Candice Firmino de
Published: November 2019

O gênero romance, desde seu surgimento e consolidação em meados do século XVIII, ocupa um espaço de experimentação que o permite questionar regras de produção consideradas tradicionais, assumindo um papel de destaque na construção de uma literatura que reflete os movimentos discursivos dos tempos. Os deslocamentos culturais, as interseções com elementos diversos da cultura escrita e a mobilidade das relações sociais na modernidade são refletidos na linguagem romanesca e refratados como discurso de um gênero considerado rebelde quanto aos seus próprios limites. Como elemento moderador das vozes presentes no discurso romanesco, percebemos o narrador e sua habilidade em estabelecer um diálogo com o espaço ficcional e os elementos que compõem a teia da narrativa. Atravessados pelos estudos pós-coloniais, da filosofia da linguagem, da estética e da sociologia, propomos aqui uma discussão acerca do narrador como elemento discursivo na construção do romance na modernidade.
How to… support residents and staff during the winter
Authors: Ashurst Adrian
Published: November 2019

Winter is one of the most difficult periods for healthcare services across the board. For care homes, this is no different. Adrian Ashurst shares his ideas to help care home managers prepare for the cold months ahead
Beliefs and attitudes of health workers to influenza vaccination: a survey
Authors: King Andrea , Doherty Tracy , Quintyne Keith Ian , Brabazon Elaine
Published: November 2019

Flu season has arrived, and with it comes the increased risk of health professionals infecting those under their care. It is vital, therefore, that barriers that may deter healthcare professionals from being vaccinated are addressed. Researchers at Ireland's Department of Public Health presents its fascinating findings about these obstacles and how to overcome them
Managing lymphoedema in patients with dementia: how to address compliance
Authors: Stoney Josephine
Published: November 2019

As practitioners, the primary goal is to do the best for patients by giving information and advice and helping them towards a positive outcome. However, patient compliance is not always easily achieved. Josephine Stoney explores some of the factors that may affect this, particularly for a patient with dementia and lymphoedema
Training staff to develop meaningful activities for older people
Authors: Ashurst Adrian
Published: November 2019

Appreciating residents' individuality is a key aspect of care, and one way to do this is to help them cultivate their hobbies. Adrian Ashurst explains how staff can be trained to enhance residents' quality of life through arranging activities and entertainment
Phytochemical and Antibacterial Properties of Ethanolic Seed Extracts of Chrysophyllum albidum (African Star Apple)
Authors: Oputah Samuel L. , Ajanaku Kolawole O. , Mordi Raphael C. , Olugbuyiro Joseph A. O. , Olorunshola Shade J. , Azuh Dominic E.
Published: November 2019

Phytochemical and antibacterial properties of ethanolic extract of the seeds of African Star Apple (Chrysophyllum albidum) were investigated. The phytochemical result revealed the presence of saponins, carbohydrates, flavonoids, quinones, cardiac glycosides, fatty acids and terpenoids. The antibacterial activity was studied using agar well diffusion method at different concentrations against six pathogenic bacterial strains, three Gram-positive (Staphylococcus aureus, Micrococcus varians and Bacillus cereus) and three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris). Significant inhibitory activities were exhibited by the ethanolic seed extracts for all test organisms except Bacillus cereus. Zone of inhibition of the crude ethanolic extract was correlated with that of a standard antibiotic Gentamicin, for antibacterial activity. The results indicated a notable inhibition of the bacterial growth.
Photoluminescence Properties of Eu3+ and Ce3+ Activated Calcium Chlorophosphate Via Combustion Synthesis Method
Authors: Baig Nahida , Dhoble N. S. , Kokode N. S. , Dhoble S. J.
Published: November 2019

Calcium chlorophosphate (Ca2PO4Cl) phosphors, activated by rare earth ions Eu3+ and Ce3+ were prepared by urea assisted combustion synthesis technique and their characterization and luminescent properties were studied. The synthesized phosphors were investigated by powdered XRD, SEM and Photoluminescence characterization (PL) methods. PL excitation spectra of Ca2PO4Cl:Eu3+/Ce3+ phosphor exhibit narrow bands in the near ultra violet (n-UV) range, and the PL emission spectra of Ca2PO4Cl: Eu3+/Ce3+ phosphor shows sharp narrow bands typical of rare earth ions. The bands observed in the PL emission and excitation spectra of Ca2PO4Cl: Eu3+/Ce3+ phosphors can be ascribed to the electronic transitions within 4f configurations of rare earth ions. The excitation peaks for Ca2PO4Cl: Eu3+ is in n-UV range. The obtained results suggest that these phosphors may be favorable for lamp industry.
Task Scheduling Problem Using Fuzzy Graph
Authors: Raich Vivek , Rai Shweta
Published: November 2019

The concept of obtaining fuzzy sum of fuzzy colorings problem has a natural application in scheduling theory. The problem of scheduling N jobs on a single machine and obtain the minimum value of the job completion times is equivalent to finding the fuzzy chromatic sum of the fuzzy graph modeled for this problem. The aim of this paper is to solve task scheduling problems using fuzzy graph.
On the Estimation of Population Mean Under Systematic Sampling Using Auxiliary Attributes
Authors: Shahzad Usman
Published: November 2019

Naik and Gupta (1996), Singh et al. (2007) and Abd-Elfattah et al. (2010) introduced some estimators for estimating population mean using available auxiliary attributes under simple random sampling scheme. We adapt these estimators under systematic random sampling scheme using available auxiliary attributes. Further, a new family of estimators is proposed for the estimation of population mean under systematic random sampling scheme. The properties such as bias and mean square error of the proposed estimators are derived. From numerical illustration it is shown that proposed estimators are more efficient than the reviewed ones.
Aplicação de Foresight e Inteligência Competitiva em um Centro de P&D Empresarial por meio de um Observatório de Tendências: desafios e benefícios
Authors: Parreiras Viviane Masseran Antunes , Antunes Adelaide Maria de Souza
Published: November 2019

DOI: http://dx.doi.org/10.13071/regec.2317-5087.2012.1.1.3908.55-73O artigo inicia-se apresentando os conceitos relacionados aos processos de foresight e inteligência competitiva, bem como suas respectivas metodologias, procurando mostrar como estas podem ser aplicadas em um centro de P&D empresarial, por meio da implantação de um observatório de tendências tecnológicas. São evidenciados os principais aspectos e as variáveis a serem consideradas na construção de um observatório de tendências, indicando o papel dos processos de foresight e inteligência competitiva, bem como ressaltando os desafios e benefícios potenciais que podem ser vivenciados pelas instituições no momento da implementação de observatórios de tendências em centros de P&D empresariais.
Metamorfoses Paulistanas: atlas geoeconômico da Cidade
Authors: Freire Carlos Eduardo Torres , Consoni Flávia Luciane
Published: November 2019

DOI: http://dx.doi.org/10.13071/regec.2317-5087.2012.1.1.4111.210-217“Metamorfoses Paulistanas” traz uma análise que contempla de forma coordenada transformações econômicas e territoriais do município de São Paulo. É, portanto, uma análise com foco na cidade de São Paulo, porém seus achados extrapolam esta delimitação territorial. A cidade é tanto influenciada pela dinâmica das suas regiões fronteiriças, quanto estas regiões ajudam a determinar a trajetória e as características da dinâmica econômica da Capital Paulista.
Proposta de Disciplina de Propriedade Intelectual a partir de Práticas de Ensino em Instituições Selecionadas
Authors: Nunes Gimenez Ana Maria , Machado Bonacelli Maria Beatriz , Carneiro Ana Maria
Published: November 2019

DOI: http://dx.doi.org/10.13071/regec.2317-5087.2013.2.2.4587.52-74O presente artigo apresenta questões abordadas em trabalho desenvolvido na Universidade Estadual de Campinas (Unicamp) e que dizem respeito ao ensino da propriedade intelectual. Partiu-se da análise de iniciativas internacionais e nacionais (“boas práticas” no ensino da PI), bem como das recomendações da Organização Mundial da Propriedade Intelectual (OMPI), de referencial teórico e de estudo de caso – a Unicamp, o que permitiu a proposição de curso/disciplina sobre propriedade intelectual como contribuição às discussões sobre o tema.