bluuebunny/crossref_metadata_2025 huggingface dataset:
Worn tool geometry–based flank wear prediction in micro turning
Authors: Elias Jiju V , Asams S , Mathew Jose
Published: December 2019

Mechanical micromachining techniques have gained much popularity in the manufacturing of microcomponents with complex shapes in the past couple of decades. Machining at the microscale poses several challenges such as size effect, which highly influences the material deformation mechanism resulting in a nonlinear variation in specific cutting energy, which accelerates the tool wear. Since micromachining is associated with micro-features, high precision and tight tolerances, the prediction of tool wear in advance is essential. Calibrated tool-wear models are generally used for the prediction of tool wear in the macro machining regime, whereas the applicability of these tool-wear models in the microscale machining is not explored much in the past. In the present work, Usui tool-wear model and worn tool geometry–based Malakizadi model are calibrated for the tool flank wear prediction during micro turning of Ti-6Al-4V alloy, using a hybrid approach involving both finite element simulations and cutting experiments. The validation experiments show that both the models can satisfactorily predict the tool-wear rate during micro turning with a percentage error of less than 15%. Results indicate that the worn tool geometry–based tool-wear model outperforms the conventional Usui model as it incorporates the instantaneous tool geometry, which also makes it suitable for different tool geometries.
Use of Letter Names Benefits Young Children’s Spelling
Authors: Treiman Rebecca , Wolter Sloane
Published: December 2019

We studied how children begin to produce spellings that reflect the sounds in words. We asked 75 U.S. preschoolers (mean age = 4 years, 11 months) to participate in two sessions. In one session, the children were asked to spell words (e.g., bead) that begin with a sequence of sounds that matches the name of a letter; in another session, they were asked to spell control words (e.g., bed). The phonological plausibility of children’s spellings, particularly their spellings of the words’ first phonemes, was higher for letter-name words than for control words. When we categorized spelling performance in a session as prephonological if the child used phonologically appropriate letters no more often than would be expected by chance, we found that children were more likely to be prephonological spellers in the session with control words than in the session with letter-name words. Words with letter names can help children move from prephonological spellings to spellings that symbolize at least some of the sounds in words.
Book review: Giulia Battaglia, Documentary Film in India: An Anthropological History
Authors: Matzner Deborah
Published: December 2019

Giulia Battaglia, Documentary Film in India: An Anthropological History. London and New York, NY: Routledge, 2018, 248 pp., $82.25. ISBN: 978–1–13855173–2.
Book review: Ashvin Immanuel Devasundaram, India’s New Independent Cinema: The Rise of the Hybrid
Authors: Chatterjee Tupur
Published: December 2019

Ashvin Immanuel Devasundaram, India’s New Independent Cinema: The Rise of the Hybrid. New York, NY: Routledge, 2016, 292 pp., ISBN: 978-1-138-18462-6.
Segmental arterial mediolysis (SAM): Systematic review and analysis of 143 cases
Authors: Skeik Nedaa , Olson Sydney L , Hari Gopika , Pavia Mary L
Published: December 2019

Segmental arterial mediolysis (SAM) is a rare but serious nonatherosclerotic, noninflammatory vasculopathy of unknown etiology that often results in dissection, aneurysm, occlusion, or stenosis of, primarily, the abdominal arteries. Current literature lacks consensus on diagnostic criteria and management options for SAM. This review summarizes 143 cases and aims to advance appropriate recognition and management of SAM. Literature review of all relevant SAM case studies from 2005 to 2018 yielded 126 individual SAM cases from 66 reports. We identified 17 additional SAM cases from our center, bringing our analysis to 143 patients. Patients with SAM were most commonly men (68%) in their 60s. Hypertension (43%), tobacco use (12%), and hyperlipidemia (12%) were common comorbidities. Abdominal pain (80%) and intraabdominal bleeding (50%) were the most common presenting symptoms. Computed tomography was the most frequently used imaging method (78%), and histology was available in 44% of cases. The most commonly affected vessels were the superior mesenteric (53%), hepatic (45%), celiac (36%), renal (26%), and splenic (25%) arteries with aneurysm (76%), dissection (61%), and arterial rupture (46%). Treatments included coil embolization (28%), abdominal organ surgery (24%), open arterial repair (21%), and medical management (20%). Case-specific treatment modalities yielded symptom relief in the vast majority (91%) of patients, with a mortality rate of 7%.
Reconciling an irreconcilable past: Sexuality, autoethnography, and reflecting on the stigmatization of the ‘unspoken’
Authors: Javaid Aliraza
Published: December 2019

I demonstrate the ways in which constructions of knowledge about sexual violence metaphorically and symbolically transpose stigma onto me for researching a stigmatized topic. In every human interaction, we all run the risk of stigma. I was stigmatized for revealing my association with the topic of sexual violence. In this article, I detail certain encounters of running into this stigma, using autoethnography. Drawing on Sara Ahmed’s poetic writings in this piece, to name a problem as a problem is to become a problem; the problems I highlight in my life turn me into a problem. I provide some of the implications that developed from highlighting such problems, such as suffering disbelieving and hostile attitudes and responses, rape threats, and derogatory comments from the wider society. I offer suggestions for other gender and sexuality writers as to how to reduce or manage stigma from looming large, for to not do so, one could be susceptible to ongoing abuse, derogatory and degrading comments, and, in some cases, threats of – and actual – violence and abuse.
Exploring perceptions on medical app use in clinical communication among Austrian physicians: Results of a validation study
Authors: Haluza Daniela , Hofer Fanni
Published: December 2019

Physicians increasingly use medical applications to facilitate clinical information management. The respective effect on clinical communication and quality of healthcare provision has not been studied in the Austrian context so far. Thus, the current cross-sectional online study analyzed prevalent medical applications use and views on clinical communication competence in everyday medical practice among Austrian physicians (n = 151) and validated the survey tool. More than half of the participants used medical applications in daily clinical practice. The top three benefits of medical applications use were higher quality of healthcare, location-independent health service access, and higher efficiency in healthcare resource allocation. Moreover, study participants felt that communication competence acquired during medical studies inadequately prepared them for daily clinical practices. Medical applications use certainly affects the therapeutic alliance between patients and physician. This study supports the importance of initiating an open, constructive discussion among healthcare stakeholders and developing according to evidence-based guidelines.
A comparative study of the utilisation of an electronic test–result management system in emergency and intensive care settings
Authors: Thomas Judith , Dahm Maria R , Li Julie , Westbrook Johanna I , Georgiou Andrew
Published: December 2019

The purpose of this qualitative study was to identify differences in the utilisation of an electronic medical record test–result management system between two acute care departments. Field observations (130 min) and semi-structured interviews (n = 24) were conducted in the Intensive Care Unit and Emergency Department of an Australian hospital. Work processes identified from audio transcripts were modelled using business process modelling. Comparison of the Emergency Department and Intensive Care Unit identified the following: (1) test ordering variations according to clinical roles, (2) differences in the use of electronic medical record functionality according to specific demands of the clinical environment and (3) the non-linear components of the test–result management process. Variations were identified in the number of process decisions, external collaborations and temporal process workflows. Modelling the business processes, collaboration and communication needs of individual clinical environments can aid in enhancing the quality and appositeness of health information technology interventions and thus contribute to improving patient safety. Future health information technology interventions/evaluations aimed at improving the safety of test–result management processes need to address both the nuances of the clinical environment and accommodate the individual work practices of clinicians within that environment.
The efficiency analysis and spatial implications of health information technology: A regional exploratory study in China
Authors: Li Dan , Chao Jianqian , Kong Jing , Cao Gui , Lv Mengru , Zhang Man
Published: December 2019

The new adoption of healthcare information technology is costly, and effects on healthcare performance can be questionable. This nationwide study in China investigated the efficient performance of healthcare information technology and examined its spatial correlation. Panel data were extracted from the Annual Investigation Report on Hospital Information in China and the China Health Statistics Yearbook for 2007 through 2015 (279 observations). Stochastic frontier analysis was employed to estimate the technical efficiency of healthcare information technology performance and related factors at the regional level. Healthcare information technology performance was positively associated with electronic medical records, total input, and cost of inpatient stay, while picture archiving and communication systems and net assets were negatively related. Local Indicators of Spatial Association showed that there existed significant spatial autocorrelation. Governmental policies would best make distinctions among different forms of healthcare information technology, especially between electronic medical records and picture archiving and communication systems. Policies should be formulated to improve healthcare information technology adoption and reduce regional differences.
“Smart” Cameras and the Operational Enclosure
Authors: Andrejevic Mark , Volcic Zala
Published: December 2019

Concerns about the impending implementation of facial recognition technology in public and shared spaces go beyond privacy to include the changing relationship between space and power. This article explores the relationship between automated identification and social sorting, decision-making, and response. To develop a theoretical framework for considering the ways in which facial recognition technology reconfigures power relations, the article considers the effects of treating the face as what Harun Farocki calls an “operative image”: not a representation, but part of a sequence of operations. These operations deprive the face of its distinctive character to facilitate the automated governance of space. For Foucault, environmentality focused on the governance of populations, but digital technology individualizes and particularizes this process. Facial recognition technology raises issues of public concern not simply because it changes the conditions of privacy and recognition in shared spaces, but because it enables new modes of automated control.
Applying Multiple Methods of Systematic Evaluation in Narrative Analysis for Greater Validity and Deeper Meaning
Authors: Meraz Rebecca Lynn , Osteen Kathryn , McGee Jocelyn
Published: December 2019

Personal narrative is at the heart of how human beings share information, represent identity, and convey ideas. Narrative research is a form of qualitative analysis that assists researchers in gaining insight into the lived experiences of the persons they are studying within their unique life circumstances and contexts. Although many narrative investigations report themes from study data, there is no single, well-defined approach to data analysis in narrative research. In this article, we provide a method for analyzing the data beyond the spoken words by applying Riessman’s thematic, structural, and performance analysis. We describe how applying multiple methods of systematic evaluation to narrative data leads to a deeper and more valid insight into the told stories. The data analysis process outlined in this article contributes to the academic discourse and knowledge supporting the use of multiple methods of systematic evaluation to uncover deeper meaning and thus leading to greater validity of the findings from narrative data.
Prognosis comparison between wait and watch and surgical strategy on rectal cancer patients after treatment with neoadjuvant chemoradiotherapy: a meta-analysis
Authors: Pang Kai , Rao Quan , Qin Shengqi , Jin Lan , Yao Hongwei , Zhang Zhongtao
Published: December 2019

Background:

After achieving a clinical complete response through neoadjuvant chemoradiotherapy, a nonoperative management approach for rectal cancer patients known as Wait and Watch (W&W) has gained increasing attention. However, the W&W strategy has been related to higher local recurrence and ambiguous long-term survival. This meta-analysis compared key prognosis indicators between W&W and surgical treatment in an effort to clarify some long-standing points of confusion.

Methods:

Pubmed, Web of Science, EMbase, Cochrane Library were searched for relevant researches comparing W&W with surgery treatment, with a time criteria set from 1 January 2002 to 4 July 2019. Endpoints were 2-year local regrowth/recurrence, 2-year distant metastasis (plus local regrowth/recurrence), 3- and 5-year disease-free survival (DFS), and overall survival (OS).

Results:

In total, nine studies with 801 patients were enrolled, of which 348 were managed by W&W and 453 by surgery. Surgery patients were further divided into a pathological complete response (pCR) group (all included patients achieved pCR) and a surgery group (consisting of both pCR and non-pCR patients without deliberate screening). Compared with the surgery group, W&W patients have higher 3- and 5-year OS, and are not inferior on 2-year local regrowth (LR), 2-year distant metastasis (DM)/DM+LR, and 3- and 5-year DFS. On the other hand, compared with the pCR group, the W&W group is inferior on 2-year LR, 3- and 5-year DFS, and 5-year OS, and not inferior on 2-year DM/DM+LR and 3-year OS.

Conclusions:

In contrast with patients undergoing surgical treatment, the W&W group has higher 3- and 5-year OS, and is not inferior on other major prognostic indicators, which, however, is based on the fact that the tumor stage in the W&W group is generally earlier. Versus surgically treated patients who acquired pCR, W&W group is inferior on all major prognostic indicators except 2-year DM/DM+LR and 3-year OS. Additionally, by comparison of cCR definitions across different studies, we conclude that implementation of the strictest cCR criteria is critical for W&W patients to acquire maximum prognostic benefit.
Hounsfield unit and its correlation with spontaneous expulsion of lower ureteric stone
Authors: Bokka Sriharsha , Jain Amit
Published: December 2019

Background:

Hounsfield unit (HU) is the measure of stone density, and is utilized in the predetermination of type of stone. The purpose of this study was to identify some factors in noncontrast computed tomography (NCCT) of kidney, ureter, and bladder (KUB) that are easily extractable and can be used to determine the outcome of expectant management.

Methods:

All patients 18–50 years of age who presented with flank pain and diagnosed as having lower ureteric calculi of size 5–10 mm by NCCT KUB were included in the study. HU of stone was calculated from the mean HU at three different regions of interest. We prescribed tamsulosin for 4 weeks as medical expulsive therapy. We divided the patients into two groups: group A included patients with successful expulsion of stone, and group B included patients who failed to pass stone. We compared age, gender, laterality, stone size in axial and coronal section of NCCT, HU of stone, blood urea, creatinine, and renal parenchymal thickness.

Results:

A total of 180 patients with lower ureteric calculus were included in the study. The mean age of patients was 34 years, with male:female ratio of 2.3:1. Of these 180 patients, 119 (66%) successfully expelled the stone and were included in group A, with the remaining 61 (34%) forming group B. In univariate analysis, longitudinal diameter of stone ( p < 0.001), transverse diameter of stone ( p < 0.001) and high HU ( p < 0.001) were significantly associated with failure of expulsion. However, in multivariate analysis only longitudinal diameter of stone ( p < 0.001) differed significantly among groups. Differences in HU ( p = 0.179) and transverse diameter of stone ( p = 0.108) did not reach significance level.

Conclusions:

Lower ureteric calculi are definitely amenable to conservative management. Longitudinal diameter of stone can be a useful parameter; however, HU and its derivatives cannot be used as a predictor of outcome.
Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing–remitting multiple sclerosis in a real-world clinical setting: PROTEC
Authors: Berger T , Brochet B , Brambilla L , Giacomini PS , Montalbán X , Vasco Salgado A , Su R , Bretagne A
Published: December 2019

Background

Patient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing–remitting multiple sclerosis (RRMS) disease.

Objective

The aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic.

Methods

PROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated.

Results

Unadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall ( n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline.

Conclusion

At 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective. Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708, https://clinicaltrials.gov/ct2/show/NCT01930708 .
Scientific Culture and the Construction of a World Leader in Science and Technology
Authors: Wang Chunfa
Published: December 2019

Scientific culture provides a solid foundation and is an important indicator of a world leader in science and technology. This article explores the meaning and structure of scientific culture and expounds its role in the development of the economy and society. It focuses on the importance of scientific culture in the construction of a world leader in science and technology through a brief review of the process of the development of global science powers. Based on that analysis, the author proposes that in China's journey to become a world leader in science and technology, we should take scientific culture as the foundation and the only way to develop our scientific cause.
The Culture of Science as a New Direction for the Development of Chinese Culture: A Review of Studies of the Culture of Science in Contemporary China
Authors: Yuan Jiangyang
Published: December 2019

The rise of studies on the culture of science at the beginning of the 21st century in China is not merely an extension of studies on the split between scientific culture and the culture of the humanities, which stemmed directly from the introduction of CP Snow's thesis into China, but also a consequence of the re-meeting, conflict and fusion of Western and Chinese cultures since the 1980s. From the perspective of cultural conflict and cultural integration, the author examines the development of studies of the culture of science and some resulting academic tensions over the past 20 years. He points out that the new direction of contemporary Chinese culture lies in the promotion of the culture of science, which is, together with the building of a culture of innovation to make the economy more prosperous, aimed at the promotion of national intelligence.
Bei Shizhang and the Establishment of the First Department of Biophysics in China
Authors: Liu Rui , Yao Qin
Published: December 2019

Bei Shizhang is known as a biologist in China. After returning from study abroad, he overrode all objections, established the Institute of Biophysics at the Chinese Academy of Sciences in July 1958 and strongly advocated for the establishment of the Department of Biophysics at the University of Science and Technology of China (USTC) in September 1958. He planned and prepared for the establishment of the department from the very beginning. In determining various operational aspects, such as enrolment planning, teacher arrangements, teaching plans and teaching objectives, he endeavoured to change the traditional model of biology education by focusing on the basic knowledge of physics and chemistry and emphasizing the concept that education was in the service of the political and military needs of the country. With these principles, he trained a large number of outstanding talents in the field of biophysics. Using material from the USTC archives and from recorded interviews, this paper describes the process of establishing the Department of Biophysics at USTC and the important role played by Bei Shizhang.
Yang Chengzong and the University of Science and Technology of China
Authors: Liu Pei , Zhang Zhihui
Published: December 2019

Yang Chengzong was a famous radiochemist and is considered the founding father of radio-chemistry in China. He was also a pioneer in the field of natural uranium technology and was one of the founders of the University of Science and Technology of China (USTC). Professor Yang planned and participated in the establishment of the university and its relocation to Hefei, Anhui Province, making indispensable contributions to the development of USTC. This article describes his more than 30 years of experience in scientific and educational endeavours at USTC and explores the important roles he played in the development of the university.
Qian Xuesen's ‘Cultural Design’ and the Development of Engineering Science at the University of Science and Technology of China
Authors: Tang Yumei , Zhu Yun
Published: December 2019

Engineering science at the University of Science and Technology of China (USTC) is hosted by its School of Engineering Science. From the perspective of scientific culture, this article examines Qian Xuesen's initial concept of engineering science and the formation of the discipline's cultural elements at USTC, such as institute–department integration (research–teaching integration), the training model, its emphasis on practice and its development as a research platform.
Comparing Public Attitudes towards Science across Provinces in China
Authors: Liu Xuan , Ren Fujun , Süerdem Ahmet , Li Xiang , Bauer Martin W
Published: December 2019

To illustrate the feature and structure of cultural authority of science in a Chinese context, this study reports on the features and current status of the cultural authority of science across China via a structural analysis of public perceptions of science as measured by cognitive, evaluative and behavioural indicators. Regional socio-economic disparity in China is significant, and we expect that disparity to give rise to diverse public attitudes to science. This study aims not only to enrich the regional data on current international efforts to compare public attitudes to science, but also to provide evidence-based research for other countries to discuss the diversity in the patterns of the cultural authority of science.
Research on the Structures and Features of Netizens' Demand for Popular Science: A Search Data Perspective
Authors: Wang Liming , Zhong Qi
Published: December 2019

Netizens' demand for popular science could be seen as one important social representation of the public demand for science popularization in the information age. Based on the information searching behaviour of netizens, this paper uses two indicators (demand strength and breadth) to analyse and describe netizens' demand for popular science. It examines the features, the intrinsic structure, the developing trends and group-to-group differences of netizens' demand for popular science. The results reflect younger, more mobile and fragmented tendencies in science communication in the information society, revealing the features of netizens' concerns and knowledge of popular science.
A Follow-up Study on Contestants in the International Science and Engineering Fair from the Chinese Mainland
Authors: Li Xiuju
Published: December 2019

Science competitions are an important part of science education. Research on students participating in science competitions is helpful for strengthening the role of the competitions in selecting and cultivating science and technology talent. The International Science and Engineering Fair (ISEF) is the world's largest pre-college science competition. This paper is a follow-up study of 70 contestants in the ISEF from the Chinese mainland (2003 to 2013). My research team emailed each of them a questionnaire to collect information on their subsequent learning and careers. The results reveal that most contestants were male; they were good at engineering, computer science and environmental science; they performed well in subsequent academic learning (70% of them won awards during their academic study, and 85% selected a major study field related to science, technology, engineering or mathematics); and the high school years is the best period in which to encourage students to pursue science-related study and careers. Based on my analysis, I offer some suggestions for cultivating young scientists.
Decaying infrastructures in the post-industrial city: An urban political ecology of the US pipeline crisis
Authors: Silver Jonathan
Published: December 2019

Infrastructure is critical to the ways in which urban inequality is produced and experienced. Across US post-industrial contexts urban infrastructures are decaying, causing problems to the capacity of various systems to deliver essential resource flows for social reproduction. This paper examines the US pipeline crisis to understand why, how and with what effects infrastructure has undergone a process of physical decay, concentrated across inner-city areas. It uses a case study of Camden, New Jersey, a poor city in which infrastructure has undergone decades of neglect, privatisation and under-maintenance. This decay has created difficulties in sustaining a safe, universal and fully functioning infrastructure. To understand these dynamics, the paper advances an urban political ecology approach to examining these infrastructural geographies. It makes three key contributions. First, it considers how to conceptualise decay and its effect on the urban circulations that have been enabled/disabled by infrastructure through the notion of unbounding. Second, given the highly segregated infrastructural experiences between a black city and white suburbs, the paper draws on recent geographic scholarship on racial capitalism, emphasising the role of race in the governing of infrastructure and in accounting for Camden’s conditions of decay. Third, the paper advances a relational theorisation that draws on concepts emanating from urban political ecology and associated research on infrastructure in cities of the global South. With the reported, widespread decay of infrastructures in global North, post-industrial contexts, a relational theorisation can draw on long-established vocabularies that challenge where we locate the ‘infrastructural South’ and prompt new political urban questions.
Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling
Authors: Yu Xin , Wan Qilong , Ye Xiaoling , Cheng Yuet , Pathak Janak L. , Li Zubing
Published: December 2019

Background

Hypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown.

Methods

In this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model.

Results

The peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and μ-CT results showed that CoCl2treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect.

Conclusions

The in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.
Renal cell carcinoma lung metastases treated by radiofrequency ablation integrated with systemic treatments: over 10 years of experience
Authors: Gonnet Alexis , Salabert Laura , Roubaud Guilhem , Catena Vittorio , Brouste Véronique , Buy Xavier , Gross Goupil Marine , Ravaud Alain , Palussière Jean
Published: December 2019

Background

To determine safety and efficacy of radiofrequency ablation (RFA) for local treatment of lung metastases of renal cell carcinoma (RCC), sequenced or combined with systemic treatments.

Methods

Retrospectively, we studied 53 patients treated by RFA for a maximum of six lung metastases of RCC. The endpoints were local efficacy, overall (OS), disease-free (DFS), pulmonary progression-free (PPFS) and systemic treatment-free (STFS) survivals, complications graded by the CTCAE classification and factors associated with survivals. Potential factors analysed were: clinical and pathological data, tumoral staging of TNM classification, primary tumor histology, Fuhrman’s grade, age, number and size of lung metastases and extra-pulmonary metastases pre-RFA.

Results

One hundred metastases were treated by RFA. Median follow-up time was 61 months (interquartile range 90–34). Five-year OS was 62% (95% confidence interval (CI): 44–75). Median DFS was 9.9 months (95% CI: 6–16). PPFS at 1 and 3 years was 58.9% (95%CI: 44.1–70.9) and 35.2% (95%CI: 21.6–49.1), respectively. We observed 3% major complications (grade 3 and 4 of CTCAE classification). Local efficacy was 91%. Median STFS was 28.3 months. Thirteen patients (25%) with lung recurrence could be treated by another RFA. T3/T4 tumors had significantly worse OS, PPFS and STFS. Having two or more lung metastases increased the risk of pulmonary progression more than threefold.

Conclusion

Integrated to systemic treatment strategy, RFA is safe and effective for the treatment strategy of lung metastasis from RCC with good OS and long systemic treatment-free survival. RFA offers the possibility of repeat procedures, with low morbidity.
Correction to: LC3B globular structures correlate with survival in esophageal adenocarcinoma
Authors: El-Mashed Shereen , O’Donovan Tracey R. , Kay Elaine W. , Abdallah Ayat R. , Cathcart Mary-Clare , O’Sullivan Jacintha , O’Grady Anthony , Reynolds John , O’Reilly Seamus , O’Sullivan Gerald C. , McKenna Sharon L.
Published: December 2019

Following publication of the original article [1], the authors reported an omission in the affiliations.
Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness
Authors: Rutkowska Daria A. , Mokoena Nobalanda B. , Tsekoa Tsepo L. , Dibakwane Vusi S. , O’Kennedy Martha M.
Published: December 2019

Background

African horse sickness (AHS) is a severe arthropod-borne viral disease of equids, with a mortality rate of up to 95% in susceptible naïve horses. Due to safety concerns with the current live, attenuated AHS vaccine, alternate safe and effective vaccination strategies such as virus-like particles (VLPs) are being investigated. Transient plant-based expression systems are a rapid and highly scalable means of producing such African horse sickness virus (AHSV) VLPs for vaccine purposes.

Results

In this study, we demonstrated that transient co-expression of the four AHSV capsid proteins in agroinfiltrated Nicotiana benthamiana dXT/FT plants not only allowed for the assembly of homogenous AHSV-1 VLPs but also single, double and triple chimeric VLPs, where one capsid protein originated from one AHS serotype and at least one other capsid protein originated from another AHS serotype. Following optimisation of a large scale VLP purification procedure, the safety and immunogenicity of the plant-produced, triple chimeric AHSV-6 VLPs was confirmed in horses, the target species.

Conclusions

We have successfully shown assembly of single and double chimeric AHSV-7 VLPs, as well as triple chimeric AHSV-6 VLPs, in Nicotiana benthamiana dXT/FT plants. Plant produced chimeric AHSV-6 VLPs were found to be safe for administration into 6 month old foals as well as capable of eliciting a weak neutralizing humoral immune response in these target animals against homologous AHSV virus.
Silencing lncRNA ZFAS1 or elevated microRNA-135a represses proliferation, migration, invasion and resistance to apoptosis of osteosarcoma cells
Authors: Zhao Zilong , Lin Xiafei , Tong Yunhui , Li Wenxia
Published: December 2019

Background

Osteosarcoma (OS) is still a disease with high mortality from malignant tumors in children and adolescents. Due to its poor treatment, this study explored the involvement of lncRNA ZFAS1/microRNA-135a (miR-135a)/apurinic/apyrimidinic exonuclease 1 (APEX1) axis in the regulation of OS growth and metastasis.

Methods

ZFAS1, miR-135a and APEX1 expression in OS tissues and cells were tested by RT-qPCR and western blot analysis. MG63 cells were transfected with sh-ZFAS1, miR-135a mimic or their controls to unearth theirs functions in the proliferation, colony formation, migration, invasion, cycle entry and apoptosis of MG63 cells by MTT and EdU, colony formation assays, flow cytometry, and Transwell assay, severally. The proliferation related factor (Ki-67, CyclinD1), apoptosis related factor (Bax, Bcl-2) and migration related factor (MMP2, MMP9) protein levels were tested. Tumor volume and weight were detected by subcutaneous tumor xenograft in nude mice.

Results

Overexpressed ZFAS1 and APEX1, and down-regulated miR-135a existed in OS tissues and cells. Silenced ZFAS1 or elevated miR-135a inhibited colony formation and proliferation, cycle progression, migration and invasion while promoted apoptosis of MG63 cells. Silenced ZFAS1 or elevated miR-135a suppressed tumor volume and weight of OS in vivo. LncRNA ZFAS1 promoted APEX1 expression by competitively binding with miR-135a.

Conclusion

This study indicates that silenced ZFAS1 or up-regulated miR-135a restrained migration, proliferation and invasion and promoted apoptosis of OS MG63 cells. This study provides a possible theoretical basis for studying the regulatory mechanism of ZFAS1/miR-135a/APEX1 signaling axis on the growth and metastasis of OS.
Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1
Authors: Huang Hui , Cui Guiyun , Tang Hai , Kong Lingwen , Wang Xiaopeng , Cui Chenchen , Xiao Qihua , Ji Huiming
Published: December 2019

This study aimed to evaluate the specific regulatory roles of microRNA-146a (miRNA-146a) in temporal lobe epilepsy (TLE) and explore the related regulatory mechanisms. A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine. These model rats were injected intracerebroventricularly with an miRNA-146a inhibitor and Notch-1 siRNA. Then, neuronal damage and cell apoptosis in the cornu ammonis (CA) 1 and 3 regions of the hippocampus were assessed. SOD and MDA levels in the hippocampus were detected by chromatometry, and IL-1β, IL-6, and IL-18 levels were detected by ELISA. Then, we evaluated the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus. The interaction between Notch-1 and miRNA-146a was assessed by a dual luciferase reporter gene assay. A rat model of TLE was successfully established, which exhibited significantly increased miRNA-146a expression in the hippocampus. Silencing of miRNA-146a significantly alleviated the neuronal damage and cell apoptosis in the CA1 and CA3 regions of the hippocampus in TLE rats and decreased MDA, IL-1β, IL-6, and IL-18 levels and increased SOD levels in the hippocampus of TLE rats. In addition, silencing of miRNA-146a significantly decreased the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus of TLE rats. Notch-1 was identified as a target of miRNA-146a and silencing of Notch-1 aggravated the neuronal damage in the CA1 and CA3 regions. Silencing of miRNA-146a alleviated the neuronal damage in the hippocampus of TLE rats by down-regulating Notch-1.
Acute pain management in children: a survey of Italian pediatricians
Authors: Marseglia Gian Luigi , Alessio Maria , Da Dalt Liviana , Giuliano Maria , Ravelli Angelo , Marchisio Paola
Published: December 2019

Background

Current guidelines recommend assessing and relieving pain in all children and in all instances; yet, in clinical practice, management is frequently suboptimal. We investigated the attitude of Italian family pediatricians towards the evaluation and treatment of different types of acute pain in children aged 7–12 years.

Methods

This is a cross-sectional study based on a 17-question survey accessible online from October 2017 to October 2018. Responders had to describe cases of children suffering from any type of acute pain among headache, sore throat, musculoskeletal/post-traumatic pain, and earache. Children’s characteristics, pain assessment modalities and therapeutic approaches were queried. The following tests were used: Z-proportion to evaluate the distribution of categorical data; chi-squared and Kruskall-Wallis to explore data heterogeneity across groups; Mann-Whitney for head-to-head comparisons.

Results

Overall, 929 pediatricians presented 6335 cases uniformly distributed across the types examined. Pain was more frequently of moderate intensity (42.2%,P < 0.001) and short duration (within some days: 98.4%,P < 0.001). Only 50.1% of responders used an algometric scale to measure pain and 60.5% always prescribed a treatment. In children with mild-moderate pain (N = 4438), the most commonly used first-line non-opioids were ibuprofen (53.3%) and acetaminophen (44.4%). Importantly, a non-recommended dosage was prescribed in only 5.3% of acetaminophen-treated cases (overdosing). Among the misconceptions emerged, there were the following: i) ibuprofen and acetaminophen have different efficacy and safety profiles (when choosing the non-opioid, effectiveness weighted more for ibuprofen [79.7% vs 74.3%,P < 0.001] and tolerability for acetaminophen [74.0% vs 55.4%,P < 0.001]); ii) ibuprofen must be taken after meals to prevent gastric toxicities (52.5%); ibuprofen and acetaminophen can be used combined/alternated for persisting mild-moderate pain (16.1%). In case of moderate-severe pain not completely controlled by opioids, ibuprofen and acetaminophen were the most used add-on medications, with ibuprofen being much more prescribed than acetaminophen (65.2% vs 23.7%, respectively) overall and in all pain types.

Conclusions

Several gaps exist between the current practice of pain assessment and treatment and recommendations. Further efforts are needed to raise awareness and improve education on the possible exposure of the child to short- and long-term consequences in case of suboptimal pain management.
NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer
Authors: Jacobs Samuel A. , Robidoux André , Abraham Jame , Pérez-Garcia José Manuel , La Verde Nicla , Orcutt James M. , Cazzaniga Marina E. , Piette Fanny , Antolín Silvia , Aguirre Elena , Cortes Javier , Llombart-Cussac Antonio , Di Cosimo Serena , Kim Rim S. , Feng Huichen , Lipchik Corey , Lucas Peter C. , Srinivasan Ashok , Wang Ying , Song Nan , Gavin Patrick G. , Balousek April D. , Paik Soonmyung , Allegra Carmen J. , Wolmark Norman , Pogue-Geile Katherine L.
Published: December 2019

Purpose

The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2+) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses.

Experimental design

pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A). Pre-treatment biopsies and residual tumors were also compared to identify molecular changes.

Results

The numerical pCR rate in the trastuzumab plus neratinib arm (50% [95%CI 34–66%]) was greater than that for single-targeted therapies with trastuzumab (38% [95%CI 24–54]) or neratinib (33% [95%CI 20–50]) in the overall cohort but was not statistically significant. Hormone receptor-negative (HR−) tumors had a higher pCR rate than HR+tumors in all three treatment arms, with the highest pCR rate in the combination arm. Diarrhea was the most frequent adverse event and occurred in virtually all patients who received neratinib-based therapy. Grade 3 diarrhea was reported in 31% of patients; there were no grade 4 events. Our 8-gene signature, previously validated for trastuzumab benefit in two different clinical trials in theadjuvantsetting, was correlated with pCR across all arms of NSABP FB-7. Specifically, patientspredictedto receive no trastuzumab benefit had a significantly lower pCR rate than did patientspredictedto receive the most benefit (P = 0.03). FCGR genotyping showed that patients who were homozygous for the Fc low-binding phenylalanine (F) allele forFCGR3A-158V/Fwere less likely to achieve pCR.

Conclusions

Combining trastuzumab plus neratinib with paclitaxel increased the absolute pCR rate in the overall cohort and in HR−patients. The 8-gene signature, which is validated for predicting trastuzumab benefit in the adjuvant setting, was associated with pCR in the neoadjuvant setting, but remains to be validated as a predictive marker in a larger neoadjuvant clinical trial. HR status, and theFCGR3A-158V/Fgenotype, also warrant further investigation to identify HER2+patients who may benefit from additional anti-HER2 therapies beyond trastuzumab. All of these markers will require further validation in the neoadjuvant setting.

Trials registration

ClinicalTrials.gov,NCT01008150. Retrospectively registered on October 5, 2010.
Improvement in catalytic activity and thermostability of a GH10 xylanase and its synergistic degradation of biomass with cellulase
Authors: You Shuai , Xie Chen , Ma Rui , Huang Huo-qing , Herman Richard Ansah , Su Xiao-yun , Ge Yan , Cai Hui-yi , Yao Bin , Wang Jun , Luo Hui-ying
Published: December 2019

Background

Xylanase is one of the most extensively used biocatalysts for biomass degradation. However, its low catalytic efficiency and poor thermostability limit its applications. Therefore, improving the properties of xylanases to enable synergistic degradation of lignocellulosic biomass with cellulase is of considerable significance in the field of bioenergy.

Results

Using fragment replacement, we improved the catalytic performance and thermostability of a GH10 xylanase, XylE. Of the ten hybrid enzymes obtained, seven showed xylanase activity. Substitution of fragments, M3, M6, M9, and their combinations enhanced the catalytic efficiency (by 2.4- to fourfold) as well as the specific activity (by 1.2- to 3.3-fold) of XylE. The hybrids, XylE-M3, XylE-M3/M6, XylE-M3/M9, and XylE-M3/M6/M9, showed enhanced thermostability, as observed by the increase in the T50 (3–4.7 °C) and Tm (1.1–4.7 °C), and extended t1/2 (by 1.8–2.3 h). In addition, the synergistic effect of the mutant xylanase and cellulase on the degradation of mulberry bark showed that treatment with both XylE-M3/M6 and cellulase exhibited the highest synergistic effect. In this case, the degree of synergy reached 1.3, and the reducing sugar production and dry matter reduction increased by 148% and 185%, respectively, compared to treatment with only cellulase.

Conclusions

This study provides a successful strategy to improve the catalytic properties and thermostability of enzymes. We identified several xylanase candidates for applications in bioenergy and biorefinery. Synergistic degradation experiments elucidated a possible mechanism of cellulase inhibition by xylan and xylo-oligomers.
Mutational signatures in colon cancer
Authors: Pandey Priyatama , Yang Zhi , Shibata Darryl , Marjoram Paul , Siegmund Kimberly D.
Published: December 2019

Objective

Recently, many tumor sequencing studies have inferred and reported on mutational signatures, short nucleotide patterns at which particular somatic base substitutions appear more often. A number of signatures reflect biological processes in the patient and factors associated with cancer risk. Our goal is to infer mutational signatures appearing in colon cancer, a cancer for which environmental risk factors vary by cancer subtype, and compare the signatures to those in adult stem cells from normal colon. We also compare the mutational signatures to others in the literature.

Results

We apply a probabilistic mutation signature model to somatic mutations previously reported for six adult normal colon stem cells and 431 colon adenocarcinomas. We infer six mutational signatures in colon cancer, four being specific to tumors with hypermutation. Just two signatures explained the majority of mutations in the small number of normal aging colon samples. All six signatures are independently identified in a series of 295 Chinese colorectal cancers.