bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B40: High-throughput screening of new potential targets for high-grade serous ovarian cancer treatment
Authors: Dai Jun , Erkan Erdogan Pekcan , Zhang Kaiyang , Kaipio Katja , Lamminen Tarja , Huhtinen Kaisa , Hynninen Johanna , Grenman Seija , Carpen Olli Mikael , Hautaniemi Sampsa , Vähärautio Anna
Published: August 2018

High-grade serous ovarian cancer (HGSOC) is the most common cause of gynecologic-cancer-associated death. Although HGSOC is initially extremely sensitive to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen, resulting in the low 5-year survival rate of this disease. Therefore, we aim to establish a feasible methodology that combines genome editing and single-cell RNA-seq to high-throughput screen new potential targets that could be utilized alone or combined with platinum for HGSOC treatment. Firstly, we constructed several inducible Cas9-expressed HGSOC cell lines, including both platinum-sensitive and -resistant cells. Secondly, we transduced these cell lines with a pooled sgRNA lentivirus consisting of 105 non-target scrambled sgRNAs and sgRNAs against 188 genes (10 sgRNAs per gene) that are currently targets of FDA/EMA approved drugs or drugs undergoing clinical trials in ovarian cancer treatment. Our analysis of multiple HGSOC dissociated tumors by single-cell RNA-seq has revealed intertumoral heterogeneity in expression of these drug targets in vivo. The majority of these 188 genes, approximately two thirds, are expressed in low level in most epithelial ovarian cancer (EOC) cells. Only 4 genes (AKT1, IL6, C1QA, INHBA) show relatively high expression, and only in a small subset of EOC cells. Also, the remaining drug target genes that are expressed show intertumoral heterogeneity, e.g., high expression of PARP-1 in tumors that are potentially deficient in homologous recombination repair. To elucidate the functionality of these drug targets, we will next analyze the transcriptomic effects of specific gene CRISPR/Cas9 knockouts in these HGSOC cell lines by droplet-based single-cell RNA-seq. From the data, we will compare the differences between platinum-sensitive and -resistant cell lines after the gene knockouts to identify the correlations between specific genetic perturbations and platinum resistance. As a future perspective, we will continue optimizing our platform for screening other potential targets. Overall, this study provides a comprehensive and unbiased approach for potential HGSOC target screening.

Note: This abstract was not presented at the conference.

Citation Format: Jun Dai, Erdogan Pekcan Erkan, Kaiyang Zhang, Katja Kaipio, Tarja Lamminen, Kaisa Huhtinen, Johanna Hynninen, Seija Grenman, Olli Mikael Carpen, Sampsa Hautaniemi, Anna Vähärautio. High-throughput screening of new potential targets for high-grade serous ovarian cancer treatment. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B40.
Abstract IA07: Targeting micrometastasis for the treatment of ovarian cancer
Authors: Ahmed Ahmed Ashour
Published: August 2018

Unlike many other solid tumors, high-grade serous ovarian cancer seldom spreads outside the abdominal cavity. The most common cause of death is malnutrition secondary to intestinal obstruction because of abdominal metastasis. Understanding the key mechanisms involved in driving abdominal metastases is important for the development of novel strategies to prevent metastasis. In this talk, I will present our recent work on preventing ovarian cancer metastasis by targeting Salt Inducible Kinase 2 (SIK2).

Citation Format: Ahmed Ashour Ahmed. Targeting micrometastasis for the treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA07.
Abstract IA14: Exploiting synthetic lethality in the treatment of gynecologic cancers
Authors: Lord Christopher J.
Published: August 2018

PARP inhibitors represent the first synthetic lethal treatment for cancer and are now approved for the treatment of serous ovarian cancers. Despite this advance, drug resistance to PARP inhibitors is a growing problem and in most patients has an unknown etiology. I will discuss efforts to understand PARP inhibitor resistance and to devise therapeutic approaches that limit the impact of revertant BRCA1/2 mutations. I will also discuss recent data describing synthetic lethal interactions between ARID1A defects in gynecologic cancers and novel DNA repair inhibitors, including ATR inhibitors currently undergoing clinical trial assessment.

Citation Format: Christopher J. Lord. Exploiting synthetic lethality in the treatment of gynecologic cancers. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA14.
Abstract IA16: PapGene, PapSEEK, and PapDREAming for early detection of ovarian cancer
Authors: Shih Ie-Ming
Published: August 2018

Advances in genomic technologies are revolutionizing how we understand pathogenesis in ovarian cancer. These technologies are critical in developing innovative strategies to diagnose cancer earlier by detecting rare mutant alleles or aberrant methylation marks among a pool of normal DNA. Studies integrating these technologies provide the fundamental scientific underpinning for designing future standards of care to reduce the burden of ovarian cancer through early detection and prevention. This presentation will focus on two related topics. One is to summarize the recent research findings from the Johns Hopkins Ovarian Cancer Early Detection (JHOCD) group in deciphering the major molecular alterations involving in ovarian cancer in situ lesions (serous tubal intraepithelial carcinoma, STIC) and its precursors (including serous tubal intraepithelial lesion, STIL and so-called “p53” signatures) in fallopian tubes. The clinicopathologic and molecular studies we have done have helped define the precursor lesions in many high-grade serous carcinomas (HGSC) of the ovary, the most common and aggressive type of ovarian epithelial cancer. The other focus is to discuss the promise and challenges in applying genetic and epigenetic methods to detect ovarian HGSC. In an effort to replicate the success of cervical cancer screening, several approaches for the early detection of ovarian cancers have been proposed. JHOCD team has first reported the feasibility of using cervical cytology samples to detect ovarian carcinomas. We have extended this original study by determining whether different sample collection methods including cervical cytology specimens, uterine lavage/brush, and blood, alone or in combination with each other or serum CA-125 levels, can achieve a better sensitivity and specificity. The objective of JHOCD is to facilitate the proposed clinical studies to assess the clinical benefit in applying the aforementioned molecular diagnostics for early ovarian cancer diagnosis in high-risk women (including those carrying BRCA mutations).

Citation Format: Ie-Ming Shih. PapGene, PapSEEK, and PapDREAming for early detection of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA16.
Abstract IA27: Functional genetic architecture of serous ovarian cancer
Authors: Francis Kyle , Burston Helen , Mokady Daphna , Wagner Melany , Medrano Mauricio , Rottapel Robert
Published: August 2018

The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and whole-kinome proteomics to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. We have identified essential kinases that manage biosynthetic stress indicative of the ovarian cancer transformed state. These data suggest that targeting pathways that underlie adaptation to cellular stress states rather than driver oncogenes may provide new therapeutic avenues for treating HGSC.

Citation Format: Kyle Francis, Helen Burston, Daphna Mokady, Melany Wagner, Mauricio Medrano, Robert Rottapel. Functional genetic architecture of serous ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA27.
Abstract A19: Establishment of in vitro and in vivo models of inflammatory myofibroblastic tumor
Authors: Xie Jinhan (Angela) , Mould Emily V. A. , Fordham Ashleigh , Gifford Andrew J. , Trahair Toby , Mackenzie Karen L.
Published: August 2018

Inflammatory myofibroblastic tumors (IMTs) are sarcomas of soft tissue that most commonly arise in children, adolescents, and young adults. If not cured by surgery, IMT has a high propensity for local recurrence as multifocal nodules, and may rapidly progress to fatal disease. Anaplastic Lymphoma Kinase (ALK) driven tumorigenesis is implicated in approximately 50% of IMT cases. IMT patients with ALK rearrangement have been reported to respond to the ALK inhibitor, crizotinib, but with the possibility of relapse with resistant disease. The second-generation ALK inhibitor ceritinib showed improved specificity and potency toward crizotinib-resistant tumors; however, resistant disease may still emerge. Thus, there is an urgent need for identifying alternative treatment options for ALK-driven IMT. In this study, we utilized fresh malignant ascites collected from a 9-year-old boy (IMT-1) with epithelioid inflammatory myofibroblastic sarcoma (eIMS), at diagnosis (IMT-1A) and third relapse (IMT-1D) to establish the in vitro cell culture and in vivo orthotopic patient-derived xenograft (PDX) model. Primary cell cultures were successfully established from both samples with confirmed ALK rearrangement. The PDX was established by intraperitoneal injection of cultured IMT-1D cells into nonobese diabetic severe combined immune-deficient mice with IL-2 receptor gamma chain deficiency (NSG) mice. Within 6-8 weeks of inoculation, 100% of the mice became moribund due to robust multifocal intraperitoneal tumors that grew in close association with abdominal organs, including the pancreas and small bowel. The xenograft recapitulated both morphologic and immunohistochemical features of the tumor within the patient. Positive immunohistochemical staining for ALK in a characteristic perinuclear membrane pattern and ALK gene rearrangement were also demonstrated in tumor cells cultured from peritoneal fluid of the xenografted mice. Our in vitro cultures and in vivo PDX models provide a valuable opportunity to undertake a detailed characterization of ALK-driven IMT at diagnosis and following ceritinib failure. They are ideal models for preclinical evaluation of new therapeutic approaches to the treatment of ALK-driven IMT.

Citation Format: Jinhan (Angela) Xie, Emily V. A. Mould, Ashleigh Fordham, Andrew J. Gifford, Toby Trahair, Karen L. Mackenzie. Establishment of in vitro and in vivo models of inflammatory myofibroblastic tumor [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 A19.
Abstract A21: Modeling of oncogenic chromosomal translocations of aggressive fusion-positive sarcomas by CRISPR-Cas9 genomic engineering
Authors: Spraggon Lee , Martelotto Luciano , Hmeljak Julija , Hitchman Tyler , Wang Jiang , Wang Lu , Slotkin Emily , Fan Pang-Dian , Reis-Filho Jorge , Ladanyi Marc
Published: August 2018

A prominent challenge in fusion-positive sarcoma research is that the oncogenic driver is typically a chimeric transcription factor. Although considered the disease-specific molecular drivers, these chimeric transcription factors remain challenging to target pharmacologically. An alternative approach is the elucidation of molecular pathways controlled by the oncogenic transcription factor, with the aim of identifying druggable targets.

However, many fusion-driven sarcomas have a paucity of suitable genetic models, with some lacking any patient-derived cell lines. In the situations where patient-derived cell lines are available, most have been passaged for decades, potentially adding further complexity and bias. Therefore, development of faithful model systems of oncogenic chromosomal translocations is of principal importance for these aggressive translocation-driven pediatric sarcomas.

Here, we describe a novel approach that combines CRISPR-Cas9 genomic editing technology, with homology-directed repair (HDR) to engineer, capture, and modulate the expression of chromosomal translocation products in a human cell line.

We have applied this approach to the genetic modeling of t(11;22)(q24;q12) and t(11;22)(p13;q12), translocation products of the EWSR1 gene and its 3 fusion partners FLI1 and WT1, present in Ewing's sarcoma and desmoplastic small round cell tumor, respectively. Our approach establishes an innovative platform for constructing isogenic and conditionally inducible biologically relevant models for a variety of sarcomas driven by chromosomal translocations.

Citation Format: Lee Spraggon, Luciano Martelotto, Julija Hmeljak, Tyler Hitchman, Jiang Wang, Lu Wang, Emily Slotkin, Pang-Dian Fan, Jorge Reis-Filho, Marc Ladanyi. Modeling of oncogenic chromosomal translocations of aggressive fusion-positive sarcomas by CRISPR-Cas9 genomic engineering [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 A21.
Abstract A25: Elephant p53 (EP53) enhances and restores p53-mediated apoptosis in human and canine osteosarcoma
Authors: Abegglen Lisa M. , Toruno Cristhian , Donovan Lauren N. , Robinson Rosann , Goldfeder Mor , Couldwell Genevieve , Kiso Wendy K. , Schmitt Dennis L. , Caulin Aleah F. , Maley Carlo C. , Schroeder Avi , Schiffman Joshua D.
Published: August 2018

Amplification of elephant p53 (EP53) was recently described as a potential mechanism for cancer resistance in elephants. Osteosarcoma is the most common pediatric bone tumor and also occurs frequently in pet dogs. Both human and canine osteosarcoma contain a very high rate of TP53 alterations leading to genomic instability. The purpose of our study was to determine if EP53 could enhance and/or restore p53 function in osteosarcoma and trigger p53-mediated cell death. We expressed various EP53 proteins in canine and human osteosarcoma cell lines (OSCA-40, U-2 OS, and Saos-2) by transfection or viral transduction. Expression of EP53 was confirmed by Western blot. Apoptosis of cells transfected/transduced with EP53 was compared to cells transfected/transduced with negative control vectors. Apoptosis was measured by fluorescence microscopy and caspase activity. We observed a significant increase in caspase activity (normalized to cell viability) of U-2 OS (TP53-wild type) cells expressing EP53 compared to negative control cells (p<0.0001). Saos-2 (TP53-null) and OSCA-40 cells underwent apoptosis as visualized by time-lapse fluorescence microscopy. Experiments to confirm these results with caspase activity assays are currently under way. Increased expression of p21, a direct p53 target, was observed in Saos-2 cells by Western blot. Taken together, our results indicate that EP53 enhances and restores p53-mediated apoptosis in osteosarcoma. These data suggest for the first time that EP53 can function in both human and canine osteosarcoma cells to promote cell death. Efforts to define the mechanism of action of EP53 in osteosarcoma cells are ongoing. Our results support further exploration of EP53-based osteosarcoma therapeutics for both humans and dogs.

Citation Format: Lisa M. Abegglen, Cristhian Toruno, Lauren N. Donovan, Rosann Robinson, Mor Goldfeder, Genevieve Couldwell, Wendy K. Kiso, Dennis L. Schmitt, Aleah F. Caulin, Carlo C. Maley, Avi Schroeder, Joshua D. Schiffman. Elephant p53 (EP53) enhances and restores p53-mediated apoptosis in human and canine osteosarcoma [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 A25.
Abstract IA03: Translating genomic risk into an early detection strategy for sarcoma
Authors: Pinese Mark , Ballinger Mandy , Thomas David
Published: August 2018

Sarcomas are a heterogeneous and rare group of cancers that particularly afflict younger populations. We have developed the International Sarcoma Kindred Study (ISKS) to understand the genetic basis of sarcomas as a population. The ISKS has recruited almost 2,300 families from 21 centers in 7 countries, and has clinical information on over 71,000 relatives of affected probands. Using a 72-cancer gene panel, we identified enrichment of monogenic and polygenic variation amongst sarcoma patients, and which correlated with age at first cancer diagnosis. We identified that 6-8% of subjects unselected for family history carried apparently pathogenic alleles in dominant cancer genes, and that 25% of subject carry variants of potential therapeutic significance. The correlation with family patterns or classic cancer phenotypes was inconsistent. However, panel tests are limited by both exonic gene content, and cannot capture many kinds of structural variation. We report here the initial results of whole genome sequencing on over 1,100 sarcoma probands, and case:control and age-of-onset analyses to exhaustively map sarcoma-associated rare and common germline genetic variation.

Citation Format: Mark Pinese, Mandy Ballinger, David Thomas, for the International Sarcoma Kindred Study. Translating genomic risk into an early detection strategy for 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 IA03.
Abstract IA16: Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions
Authors: Widemann Brigitte C.
Published: August 2018

Neurofibromatosis type 1 (NF1) is a common (incidence 1:2,700) inherited disorder characterized by the development of peripheral nerve sheath tumors, including plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumors (MPNST). While PN are histologically benign they can result in substantial morbidity including pain, disfigurement, and neurologic or functional deficits. Importantly, PN are at risk for transformation to MPNST with a lifetime incidence in NF1 of 15.8%.

We are evaluating the natural history of NF1 PN in children enrolled on an NCI natural history study. Patients undergo detailed clinical evaluations and longitudinal evaluation with whole body MRI to assess total body tumor burden.

Our studies confirm that PN grow most rapidly in young children and that substantial PN growth in patients ≥15 years old is infrequent and should raise concern for malignant transformation. We also identified the development of distinct nodular lesions (DNL) on MRI. These lesions appear after early childhood, frequently grow more rapidly than the surrounding PN, show a growth rate independent of age, and are avid for fluorodexyglucose on positron emission tomography. On biopsy, some of these lesions were identified as atypical neurofibromas (ANF), which were recently identified as precursor lesions to MPNST, and are characterized by CDKN2A/B loss.

We have confirmed that patients with ANF are at greater risk for MPNST and are developing strategies for the evaluation and management of patients with ANF. Surgical resection of ANF, when safely feasible, may reduce the risk for MPNST development. We recently identified that MEK inhibition results in shrinkage of most PN and are expanding our efforts to evaluate the effect of MEK inhibition on DNL and ANF.

Citation Format: Brigitte C. Widemann. Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions [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 IA16.
Abstract PR05: Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma
Authors: Kim Huen Suk , Yuan Ye X. , Bernitz Jeffrey M. , Gomes Andreia , Schaniel Christopher , Lee Dung-Fang , Lemischka Ihor R.
Published: August 2018

Osteosarcoma (OS), despite being a serious pediatric cancer with the lowest survival rate, is not well studied due to its rare occurrence. For this reason, studying OS in a patient-specific manner is more challenging. In an attempt to establish a method to study OS in a patient-specific manner, we previously generated Li-Fraumeni syndrome (LFS---a germline P53 mutation disease) patient specific iPSCs, and demonstrated that the LFS-iPSC derived mesenchymal stem cells (MSCs) and osteoblasts (OBs) can recapitulate tumorigenic phenotypes in vitro and in vivo (Lee, Kim, et al., Cell 2015). Taking advantage of this new platform, we focused on finding potential therapeutic targets. We found SFRP2 (secreted frizzled related protein 2) to be highly expressed in LFS iPSC-derived MSCs and OBs by global RNA-seq gene expression analysis. Using global transcript profiling of ectopic overexpression (OE) of sFRP2 in wild-type MSCs, we discovered that sFRP2 regulates osteoblast differentiation, cell adhesion, cell proliferation, and apoptosis-related gene sets. Further functional assays revealed that sFRP2 OE contributes to the generation of abnormal osteoblast cells, which are the cause of OS, by suppressing osteogenic alkaline phosphatase activity, mineralization, and osteogenic BMP and WNT signaling. Furthermore, ectopic OE of sFRP2 is associated with LFS mediated tumorigenesis. sFRP2 OE in MSCs and OBs facilitates cell proliferation through cell cycle alteration and increases anchorage independency. In in ovo and in vivo xenograft assays (subcutaneous and intratibial injections), the tumor size is significantly increased in sFRP2 OE group and decreased in knockdown sFRP2 group. Interestingly, we also found that sFRP2 OE augments angiogenesis in vitro and in vivo, suggesting sFRP2 has a role as a paracrine factor. In the future, we will analyze sFRP2 expression levels in human OS tissue samples to determine whether sFRP2 OE has clinical relevance. Conclusively, this study demonstrates that P53 mutation-mediated osteosarcoma exerts oncogenicity through sFRP2 overexpression and that targeting of sFRP2 is a potential therapeutic strategy for OS treatment.

This abstract is also being presented as Poster A22.

Citation Format: Huen Suk Kim, Ye X. Yuan, Jeffrey M. Bernitz, Andreia Gomes, Christopher Schaniel, Dung-Fang Lee, Ihor R. Lemischka. Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma [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 PR05.
Effect of injectable progesterone on follicular development in lactating beef cows treated with estradiol plus a low-concentration progesterone device
Authors: Pfeifer Luiz Francisco Machado , Mapletoft Reuben John , Dardawal Dinesh , Singh Jaswant
Published: August 2018

The effect of injectable progesterone was evaluated along with estradiol benzoate (EB) on the fate of the dominant follicle (DF) present in the ovary at the beginning of low progesterone-based TAI protocol. All cattle were given 500 µg cloprostenol im (PGF; Schering-Plough Animal Health for Estrumate, Pointe-Claire, QC, Canada) twice, 11 d apart, and allocated into two groups: Estradiol group (E group, n = 11) and Estradiol-Progesterone group (EP group, n = 11). Ten days after the second PGF (Day 0), all cattle were given an intravaginal progesterone device with half progesterone concentration (Cue-Mate with a single pod containing 0.78 g progesterone). Concurrently, all cattle were given 1.5 mg im of estradiol benzoate in 3 mL of canola oil and PGF im on Day 0 of the protocol in a crossover design, in which each cow received both treatments. Cows in the EP group also received 100 mg im progesterone (Sigma) in 2 mL of canola oil. On Day 8, progesterone devices were removed and all cattle were given PGF im. All statistical analyses were performed with SAS 9.0. The DF present on Day 0 ovulated in 76% (16/21) of cows from E group and 28.6% (6/21) of cows from EP group (P = 0.002). After progesterone device removal, the size of ovulatory follicle did not differ between groups (E group, 15.5 ± 0.43 mm vs EP group, 15.8 ± 0.98 mm; P = 0.82). These follicles ovulated in 81.3 ± 3.1 h in E group and 71.0 ± 6.1 h in EP group (P = 0.13). In conclusion, injectable progesterone reduced the proportion of cows that ovulate the dominant follicle present in the ovary at the beginning of estradiol-progesterone-based protocols. However, no difference was detected on time of ovulation after progesterone device removal between groups.
Use of a porous cellulose membrane (Membracel®) and moxibustion for severe excoriative injury in a chilean skua (Catharacta chilensis)
Authors: Mannina Natassia Bacco , Mello Daniela Magalhães Drummond de , Costa Priscilla Carla dos Santos , Rodrigues João Paulo Bastardo , Bertão João Victor da Silveira
Published: August 2018

The use of alternative therapeutic approaches in wild animals has gained notoriety due to its efficiency, low cost and reduced or nonexistent stressors. The present study evaluated the efficacy of treatment of a bilateral excoriative lesion in the region of the dorsal metacarpus in a Chilean skua (Catharacta chilensis) in a rehabilitation process with the use of a porous cell membrane, sold commercially, in concomitance with moxibustion sessions with herbs (Artemisia vulgaris). The healing time of 14 days was reduced when compared to traditional techniques and proved the viability and efficacy of the treatment.
Between Rupture and Continuity
Authors: Rozo Esteban
Published: August 2018

This paper explores the politics of conversion in the Colombian Amazon, comparing missionary narratives of conversion with indigenous accounts of conversion. It shows how conversion to Christianity articulates new meanings of indigeneity today in Amazonia. Using ethnographic evidence, documents and interviews, the paper demonstrates that neither the missionaries nor the indigenous populations view conversion only as rupture. Although they recognize the transformational process involved in conversion, they both emphasize cultural continuity, albeit for different reasons. It also analyses how indigenous pastors and missionaries combine narratives of rupture and narratives of continuity while articulating a new kind of indigeneity (Christian indigeneity), and a specific politics of conversion. In this context, politics of conversion articulates emergent regimes of indigeneity that postulate strong complementarities between Christianity and indigenous values.
Same Memory, Different Memorials
Authors: Loffman Reuben Alexander
Published: August 2018

Recent literature on modern martyrdom and memory has focused on cases in which individual groups remember martyrs’ sacrifices by making similar memorials to them. However, this article argues that even if members of a group agree on a martyr narrative, different memorials with diverse meanings can still be erected in memory of the martyrs concerned. This article supports its argument by exploring the case of twenty members of the Holy Ghost Fathers (Spiritans) who were killed on 1 January 1962 in Kongolo in southeastern Congo-Kinshasa. The memorials dedicated to these Spiritans differ substantively with each other by emphasizing different aspects of sacrifice and memory. This article concludes by arguing that the diversity of memorials involved in this case alerts us to the fact that the traditions associated with martyrdom do not always dominate the public memory of those who sacrifice their lives for a cause.
When the Relatively Poor Prosper: The Underdog Effect on Charitable Donations
Authors: Bradley Alex , Lawrence Claire , Ferguson Eamonn
Published: August 2018

In fundraising, it is common for the donor to see how much a charity has received so far. What is the impact of this information on (a) how much people choose to donate and (b) which charity they choose to donate to? Conditional cooperation suggests that people will donate to the charity that has received the most prior support, while the Underdog Effect suggests increased donations to the charity with the least support. Across two laboratory experiments, an online study (combined N = 494) and a qualitative survey ( N = 60), a consistent preference to donate to the charity with the least prior support was observed. Thus, the Underdog Effect was supported. We suggest people will show a preference for the underdog if there are two or more charities to donate to, one of the charities is at a disadvantage, and people have little preexisting loyalty to either charity.
Experimental study of vortex suction unit-based wall-climbing robot on walls with various surface conditions
Authors: Zhao Jianghong , Li Xin , Bai Jin
Published: August 2018

This study presents a wall-climbing robot called Vortexbot. Vortexbot has a suction unit that uses vortex flow to generate a suction force. Unlike the traditional unit based on contact-type suction, the suction unit can maintain a suction force without any contact with the wall surface. Therefore, the suction unit can provide a climbing robot with sufficient stable suction force even on walls with very rough surfaces and raised obstacles/grooves, and there is no wear and tear. Furthermore, the compressed air vents from the gap between the suction unit and the wall surface after rotating in the vortex chamber. Hence, such kind of flow direction can avoid the effect of the dust and dropped items on the wall surface. In this paper, we first introduced the vortex suction unit principle and discuss the feasibility of its application to a wall-climbing robot. Subsequently, the mechanical structure of Vortexbot was designed. After which, we surveyed the suction properties of the suction unit on a smooth wall surface. Then the functional relationship between the percentage change in the suction force and the supply flow rate was obtained. In addition, we studied the effect of the roughness and shape (a raised obstacle and groove) of the wall surface on the suction performance of the suction unit. Finally, we experimentally verified the climbing performance of Vortexbot on several kinds of walls with different surface conditions. It was confirmed that using the suction unit improves the robot’s climbing performance.
Can mountain route tourism work for the poor? Exploring worldviews from Maluti Route in the Drakensberg Region of South Africa
Authors: Mutana Sarudzai , Mukwada Geoffrey
Published: August 2018

Poverty reduction is necessary for the attainment of sustainable tourism development. Ironically, in many mountain regions, tourism destinations are concomitant with extreme poverty. Route tourism is regarded as one of the few poverty reduction options available to mountain communities. This study used the worldviews theory to compare the perceptions of the three distinct groups, namely local communities, tourism business operators and local government officials, regarding the contribution of route tourism to poverty reduction along the Maluti Route, in the Drakensberg Mountain Region of South Africa. A survey was carried out among 80 tourism business operators and 250 community members, and complimented with in-depth interviews held with local government officials and observations that were made in tourism business organisations. The results indicate diametrically opposed viewpoints between tourism business operators and local communities. While business organisations believe that they are significantly contributing to poverty reduction in the region, local communities acknowledge only a limited number of benefits from tourism. The study concludes that tourism can work for the poor if they are adequately equipped with skills to contribute in tourism investment and if the tourism cake is deliberately ‘tilted’ towards them. We conclude by highlighting the need for communication among stakeholders about current efforts and options available to reduce poverty through tourism, including the training of locals in tourism related skills, as well as improving linkages among industry, government and tourism industry as a measure for enhancing the role of tourism in poverty reduction.
Cost-minimization analysis of community pharmacy-based point-of-care testing for strep throat in 5 Canadian provinces
Authors: Lathia Nina , Sullivan Karen , Tam Kathy , Brna Margaret , MacNeil Paula , Saltmarche Deb , Agro Karen
Published: August 2018

Background:

Strep throat point-of-care (POC) testing in community pharmacies will enable pharmacist-based care for this condition. Our objective was to conduct an economic evaluation of treating severe sore throat when this service was offered in pharmacies in 5 Canadian provinces.

Methods:

We conducted 5 separate cost-minimization analyses for the provinces of Alberta, British Columbia, Nova Scotia, Ontario and Saskatchewan, from the public payer perspective, to estimate mean cost per patient of treating severe sore throat in 2 scenarios: 1) physician-based usual care in a family physician’s office, a walk-in clinic or an emergency room (ER) and 2) a new scenario where patients received care described above or in a pharmacy offering strep throat POC testing. One-way sensitivity analyses were conducted to account for model uncertainty.

Results:

Mean cost per patient for each pathway in the base-case analyses for the 5 provinces ranged from 1) $37.55 to $61.57 for family physician, 2) $37.55 to $61.57 for walk-in clinic, 3) $38.88 to $57.56 for ER and 4) $19.12 to $21.83 for pharmacy, representing savings ranging from $12.47 to $24.36 per patient for the new scenario. Approximate total cost savings range from $1.3 million to $2.6 million per year across the 5 provinces. All sensitivity analyses yielded cost savings for the new scenario.

Discussion:

Across 5 provinces, strep throat POC testing in pharmacies was cost saving compared to physician-based care. Sensitivity analyses demonstrated the robustness of these results.

Conclusions:

Funding strep throat POC testing in community pharmacies in these 5 provinces would lead to public health system cost savings and potentially improve patients’ access to care for severe sore throat.
Mainstreaming as rhetoric or reality? Gender and global health at the World Bank
Authors: Winters Janelle , Fernandes Genevie , McGivern Lauren , Sridhar Devi
Published: August 2018

Background:Over the past decade gender mainstreaming has gained visibility at global health organisations. The World Bank, one of the largest funders of global health activities, released twoWorld Development Reportsshowcasing its gender policies, and recently announced a $1 billion initiative for women’s entrepreneurship. We summarise the development of the Bank’s gender policies and analyse its financing of gender projects in the health sector. This article is intended to provide background for future research on the Bank’s gender and global health portfolio.

Methods:First, we constructed a timeline of the Bank’s gender policy development, through a review of published articles, grey literature, and Bank documents and reports. Second, we performed a health-focused analysis of publicly available Bank gender project databases, to track its financing of health sector projects with a gender ‘theme’ from 1985-2017.

Results:The Bank’s gender policy developed through four major phases from 1972-2017: ‘women in development’ (WID), institutionalisation of WID, gender mainstreaming, and gender equality through ‘smart economics’. In the more inclusive Bank project database, projects with a gender theme comprised between 1.3% (1985-1989) and 6.2% (2010-2016) of all Bank commitments.  Most funding targeted middle-income countries and particular health themes, including communicable diseases and health systems. Major gender-related trust funds were absent from both databases. The Bank reports that 98% of its lending is ‘gender informed’, which indicates that the gender theme used in its publicly available project databases is poorly aligned with its criteria for gender informed projects.

Conclusion:The Bank focused most of its health sector gender projects on women’s and girls’ issues. It is increasingly embracing private sector financing of its gender activities, which may impact its poverty alleviation agenda. Measuring the success of gender mainstreaming in global health will require the Bank to release more information about its gender indicators and projects.
The orthographic significance of the Latin name for the “Norfolk Island Hibiscus” (Malvaceae)
Authors: Mabberley David J.
Published: August 2018

A consideration of the naming of Hibiscus patersonius (Malvaceae) and similar names leads to the conclusion that such adjectival forms in specific epithets are in accordance with Classical Latin and that their “correction” to other adjectival forms or the genitive form of nouns is disruptive in botanical Latin.
Phylogenetic relationships in Malesian–Pacific Piper (Piperaceae) and their implications for systematics
Authors: Asmarayani Rani
Published: August 2018

Comprised of ~2000 spp., Piper is a major clade in the magnoliid angiosperms. Three major groups are recognized in Piper, i.e., the Neotropical, Asian and South Pacific. Unlike Neotropical Piper, relationships in the Paleotropical Piper remain enigmatic. This study evaluates the relationships within Paleotropical Piper by focusing sampling efforts in the Malesian region. This is the center of diversity of the genus in the Paleotropics, yet has been barely represented in previous phylogenetic studies. Eleven out of 14 infrageneric groups in Paleotropical Piper and 14% of the species were included in this study and their phylogenetic relationships were inferred based on nuclear (ITS, g3pdh) and chloroplast (trnL-F) regions. The goals were to test the monophyly of infrageneric groups, to examine how the main characters used to delimit these infrageneric groups have shaped classifications past and present, and to understand the origin of bisexual flowers and the shrubby habit in the predominantly dioecious Asian clade of climbers. The results show that the Asian clade is monophyletic in all phylogenies and the South Pacific clade is monophyletic in nuclear phylogenies. Within the Asian clade, species predominantly distributed west of Wallace’s Line (WWL) form a moderately/strongly supported clade in the ITS phylogeny, embedded within a grade of species from east of Wallace’s Line (EWL). The ITS phylogeny also resolves 12 and 5 clades in the WWL clade and the EWL grade, respectively. G3pdh and trnL-F phylogenies resolve some of the same clades, but some relationships among and within clades are incongruent. Almost no currently recognized infrageneric groups in Asian Piper are monophyletic. Most of the characters previously used to delimit infrageneric groups are homoplasious, including fruit type, bract type, direction of anther dehiscence, and number of anther valves. However, bract and fruit types are still of some value in that many clades in the Asian Piper are characterized by single bract and fruit types. In Paleotropical Piper, bisexual flowers have evolved numerous times in almost every clade, and shrubby habit has evolved at least six times, but is restricted to four clades in the WWL clade. The 17 clades resolved in this study are described along with their potential diagnostic characters.
Risk of Contraceptive Lapse and New Sexual Partnership Among Female University Students Traveling Internationally
Authors: Martins Summer L. , Mason Susan M. , Hellerstedt Wendy L. , Brady Sonya S.
Published: August 2018

CONTEXT

International travel is common and may influence women's sexual and reproductive health through myriad pathways. Existing studies focus on travelers’ risk of acquiring STDs, but not their pregnancy prevention behaviors. Further, it is unclear whether sexual and reproductive health outcomes observed for female travelers are associated with travel itself, because few studies compare travelers with nontravelers.

METHODS

An online survey was conducted in 2016–2017 among females attending a U.S. university who reported a history of sex with men; the sample comprised 340 students who had traveled internationally in the past three months (travelers) and 170 who intended to travel in the next three months (pretravelers). Multivariable modified Poisson regression models assessed associations between travel status and two outcomes during travelers’ recent trip or a period of similar duration for pretravelers: contraceptive lapse (incorrect or inconsistent use of any method) and new sexual partnership.

RESULTS

Travelers and pretravelers reported similar levels of contraceptive lapse (29% and 32%, respectively) and new sexual partnerships (17% and 12%). Multivariable analysis confirmed that travelers were no more likely than pretravelers to have contraceptive lapses, but indicated that they were more likely to report a new male partner (relative risk, 1.7). Most participants (80%) had a regular source of sexual and reproductive health care; 42% of travelers had seen a health care provider in preparation for their trip.

CONCLUSION

If the findings are corroborated by additional research, they may suggest a role for health care providers in students’ pretravel period.
Effect of Intermittent Normobaric Hypoxia Exposures on Acute Mountain Sickness During Acute Ascent to 3500 m in Indian Military Personnel
Authors: Bhaumik Gopinath , Dass Deepak , Ghosh Dishari , Kumar Harish , Kumar Sanjiva , Kumar Utkarsha , Sharma YK , Reddy MPK , Kumar Bhuvnesh , Singh Shashi Bala
Published: August 2018

In emergencies/war like situations, rapid deployment of army personnel into high altitude occurs without proper acclimatization. Rapid deployment of unacclimatized soldiers to high mountainous environments may cause debilitating effects on operational capabilities and development of acute mountain sickness (AMS). Altitude acclimatization is the best strategy for the prevention of AMS Use of pharmacological intervention for prevention of AMS is a common practice. The use of intermittent hypoxic exposure (IHE) is an alternative approach for altitude acclimatization and it reduces occurrence and severity of AMS is. But, the use of intermittent normobaric hypoxia exposure at sea level on occurrence of AMS after acute ascent to 3500m altitude in Indian army personnel has not been tested yet.
Exercise Responses to Metabolic Function on High Altitude Pulmonary Edema Susceptible Individuals
Authors: Halder Kaushik , Gupta RK , Pathak Anjana , Saha Montu
Published: August 2018

The study was aimed to evaluate and compare resting and exercise induced metabolic responses between acclimatized high altitude pulmonary edema (HAPE) susceptible (HAPE-s) and HAPE resistance (HAPE-r) volunteers at sea level. A group of 14 Indian soldiers volunteered for this study, divided into two groups, (i) HAPE-s, with past history of HAPE [n1 = 7; age = 33.3 ± 4.5 (M ± SD)] and (ii) HAPE-r, with prior history of repeated exposure to high altitude and without suffering HAPE [n2 = 7; age = 31.9 ± 4.2 (M ± SD)]. Respiratory frequency (fR), tidal volume (T), minute ventilation (E), oxygen consumption (O2), carbon dioxide output (CO2), heart rate (HR) and respiratory quotient (RQ) were recorded on all the volunteers during resting and exercise conditions. Ventilatory equivalent for oxygen (EqO2) and oxygen pulse (O2P) were calculated. Significant differences were observed between HAPE-s and HAPE-r volunteers in fRrest (25.3% higher), O2Prest (23.7% lower), Emax (50.9% lower) (all P<0.05), fRmax (55.7% lower), O2max (55.5% lower), O2Pmax (34.2% lower) (all P<0.01) and CO2max (42.1% lower, P<0.001). Rest of the parameters did not show any significant differences between the study groups. The study revealed that resting and exercise induced metabolic responses of HAPE-r volunteers was better as compared to acclimatized HAPE-s volunteers at sea level.
Role of Calpeptin in Amelioration of Hypobaric Hypoxia Induced Skeletal Muscle Damage in Rats: A Pilot Study
Authors: Rathor Richa , Agrawal Akanksha , Kumar Ravi , Suryakumar Geetha
Published: August 2018

Hypobaric hypoxia, a condition of low oxygen availability at high altitude, has a great impact on health via producing oxidative stress which could lead to protein modifications and skeletal muscle damage. Enhanced calpain activity has a major role in hypobaric hypoxia induced protein modifications and protein degradation in the skeletal muscle. The pilot study was designed to investigate the role of a calpain inhibitor, calpeptin in amelioration of hypoxia induced skeletal muscle damage. Male Sprague Dawley rats were exposed to hypobaric hypoxia (HH) with and without calpeptin (50 µg/kg, ip) treatment. HH exposure was given for 6 h at 25,000 ft. Following exposure, the animals were sacrificed and hind limb skeletal muscle was excised for analysis. Calpeptin administration inhibited protein oxidation (decrease protein carbonyl and AOPP content). Decrease in oxidized tryptophan and bityrosine content was also observed in calpeptin pre-treated group in comparison to HH exposed group. Beside this, HH induced reactive oxygen species (ROS) was also ameliorated via calpeptin treatment. Conclusively, calpeptin administration better maintained the oxidative homeostasis in skeletal muscle under hypobaric hypoxia and significantly protected against the protein damage and degradation. However, the exact mechanism is still unknown. Therefore, further research needs to be done to unravel the underlying mechanism.
Reclassification of Signs
Authors: Jia Hongwei
Published: August 2018

Previous semiotic research classified human signs into linguistic signs and non-linguistic signs, with reference to human language and the writing system as the core members of the sign family. However, this classification cannot cover all the types of translation in the broad sense in terms of sign transformation activities. Therefore, it is necessary to reclassify the signs that make meaning into tangible signs and intangible signs based on the medium of the signs. Whereas tangible signs are attached to the outer medium of the physical world, intangible signs are attached to the inner medium of the human cerebral nervous system. The three types of transformation, which are namely from tangible signs into tangible signs, from tangible signs into intangible signs, and from intangible signs into tangible signs, lay a solid foundation for the categorization of sign activities in translation semiotics. Such a reclassification of signs can not only enrich semiotic theories of sign types, human communication, and sign-text interpretation, but also inspire new research on translation types, the translation process, translators’ thinking systems and psychology, and the mechanism of machine translation.