bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiomyocyte contractile force changes in response to AGRWE detected by AFM
Authors: Qu YingMin , Zhao Feihu , Wang Xinyue , Liu Jinyun , Li Jingmei , Song Zhengxun , Wang Zuobin 
Published: January 2019

The cardiac contractile force is an important predictor of healthy and cardiovascular diseases. The changes of cardiomyocyte contractile force in response to American ginseng root water extract (AGRWE) detected by atomic force microscope have not been investigated yet. This study examined the effects of AGRWE on single beating cardiomyocytes extracted from a newborn rat. The same cardiomyocytes were incubated with AGRWE at a concentration of 50 μg/ml for about 30 min, and the cardiomyocytes’ contractile force increased from 1.74 ± 1.01 to 3.49 ± 1.53 nN. The mean value of the contractile strain calculated was 3.32 ± 1.55% for the cardiomyocyte before the treatment with AGRWE, while for the cardiomyocyte treated with AGRWE it increased to 4.60 ± 1.35%. The results also showed that the beating rate of the same single beating cardiomyocytes was decreased from 34 ± 11 beats/min (control, n = 10) to 20 ± 9 beats/min. In conclusion, the experimental results have shown clearly that the contractile forces and strain of single beating cardiomyocytes treated with AGRWE are significantly higher than the control group, while the heart rate was decreased. It suggests that ginseng agents are promising candidates in improving cardiac functions for treating heart failure.
Dark matter response to galaxy assembly history
Authors: Artale María Celeste , Pedrosa Susana E. , Tissera Patricia B. , Cataldi Pedro , Di Cintio Arianna 
Published: January 2019

Aims. It is well known that the presence of baryons affects the dark matter host haloes. Exploring the galaxy assembly history together with the dark matter haloes properties through time can provide a way to measure these effects.
Methods. We have studied the properties of four Milky Way mass dark matter haloes from the Aquarius project during their assembly history, between z = 0 − 4. In this work, we used a published SPH run and the dark matter only counterpart as case studies. To asses the robustness of our findings, we compared them with one of the haloes run using a moving-mesh technique and different sub-grid scheme.
Results. Our results show that the cosmic evolution of the dark matter halo profiles depends on the assembly history of the baryons. We find that the dark matter profiles do not significantly change with time, hence they become stable, when the fraction of baryons accumulated in the central regions reaches 80 per cent of its present mass within the virial radius. Furthermore, the mass accretion history shows that the haloes that assembled earlier are those that contain a larger amount of baryonic mass aforetime, which in turn allows the dark matter halo profiles to reach a stable configuration earlier. For the SPH haloes, we find that the specific angular momentum of the dark matter particles within the five per cent of the virial radius at z = 0, remains approximately constant from the time at which 60 per cent of the stellar mass is gathered. We have explored different theoretical and empirical models for the contraction of the haloes through redshift. A model to better describe the contraction of the haloes through redshift evolution must depend on the stellar mass content in the inner regions.
Comparison of Outcomes in Oncoplastic Pelvic Reconstruction with VRAM versus Omental Flaps: A Large Cohort Analysis
Authors: Chaudhry Arif , Oliver Jeremie D. , Vyas Krishna S. , Tran Nho V. , Martinez-Jorge Jorys , Larson David , Dozois Eric , Nelson Heidi , Manrique Oscar J. 
Published: January 2019

Background The purpose of this study is to describe our experience and outcomes in oncoplastic pelvic reconstruction for patients who underwent either vertical rectus abdominis musculocutaneous (VRAM) or omental flap following abdominoperineal resection (APR) at a single tertiary care institution.
Methods All patients who underwent pelvic reconstruction following APR with either VRAM or omental flaps from January 1992 to January 2017 were retrospectively reviewed. Patient demographics and relevant comorbidities including chemotherapy and radiation therapy data were collected and analyzed. In addition, margin status at the time of oncologic resection was analyzed. Flap-specific data were collected for each approach. Oncologic data collected included cancer type, stage at time of APR, and rate of tumor recurrence within the flap.
Results A total of 562 patients were identified who underwent pelvic reconstruction with either VRAM or omental pedicle flaps. Of these, 274 (48.8%) underwent VRAM reconstruction and 288 (51.2%) underwent omental flap reconstruction. All margins were negative at time of cancer ablation surgery. Complications data included: seroma (VRAM = 2 [0.36%]; omentum = 32 [5.69%], p < 0.0001), wound dehiscence (VRAM = 31 [5.52%]; omentum = 17 [3.02%], p = 0.022), abscess (VRAM = 4 [0.71%]; omentum = 27 [4.8%], p < 0.0001), cellulitis (VRAM = 2 [0.36%]; omentum = 10 [1.78%], p = 0.025). Statistical comparison of tumor recurrence between these two reconstructive approaches showed a significantly higher recurrence rate in omental flaps compared with VRAM flaps (p = 0.000127).
Conclusion The results of this study suggest a significantly higher tumor recurrence rate in omental flap pelvic reconstruction compared with VRAM flaps. This knowledge has the potential to influence surgical planning and flap selection in pelvic reconstruction.
Chromatin features constrain structural variation across evolutionary timescales
Authors: Fudenberg Geoff , Pollard Katherine S. 
Published: January 2019

Significance
Noncoding DNA sequences play crucial roles in gene regulation, including via three-dimensional genome organization where they define chromatin boundaries and segment the genome into a sequence of insulated neighborhoods. However, the relative importance of noncoding DNA elements, particularly in comparison with protein-coding DNA sequences, remains more poorly characterized. Here, we systematically test if chromatin boundary disruptions are under purifying selection. Our analyses uncover a genomewide depletion of structural variants that would have the potential to alter chromatin structure. This in turn has implications for predicting not only which variants are likely pathogenic in clinical genetics settings, but also which are likely key innovations in primate evolution, and argues for expanding the current gene-centric paradigm for interpreting structural variants.
Nonequilibrium correlations in minimal dynamical models of polymer copying
Authors: Poulton Jenny M. , ten Wolde Pieter Rein , Ouldridge Thomas E. 
Published: January 2019

Significance
The ordering of chemical units within DNA, RNA, and proteins carries information about how living cells operate, and copying these sequences accurately is vital. We have a limited understanding of the fundamental physical underpinnings of these processes, since important mechanistic constraints due to the need to separate daughter sequences from their templates have never been investigated in detail. By considering the simplest models that incorporate these constraints, we highlight their profound consequences in terms of the effort that must be expended to make accurate copies. These insights will help us to understand not only life today but also how early replicators may have functioned in the past, and how we might develop synthetic copiers in the future.
Reprogramming responsiveness to checkpoint blockade in dysfunctional CD8 T cells
Authors: Nelson Christine E. , Mills Lauren J. , McCurtain Jennifer L. , Thompson Emily A. , Seelig Davis M. , Bhela Siddheshvar , Quarnstrom Clare F. , Fife Brian T. , Vezys Vaiva 
Published: January 2019

Significance
Cancer immunotherapies, such as immune checkpoint blockade, work by stimulating immune cells to kill tumors. Unfortunately, not all patients respond to checkpoint treatment, which also causes autoimmune side effects due to self-reactive immune cell activation. This study uncovers immune subtypes that respond best to this immunotherapy and reveals methods to reinvigorate dysfunctional antitumor immune responses. We show that self-reactive CD8 T cells can be pathogenic or nonresponsive to checkpoint blockade therapy depending on their activation status. In addition, tolerant self-reactive CD8 T cells bear striking similarity to dysfunctional tumor-specific CD8 T cells. Finally, we demonstrate that previously tolerant self-specific CD8 T cells can eliminate aggressive tumors bearing self-antigens without concomitant autoimmunity after robust antigenic vaccination in concert with PD-L1 blockade.
Altered interplay between endoplasmic reticulum and mitochondria in Charcot–Marie–Tooth type 2A neuropathy
Authors: Bernard-Marissal Nathalie , van Hameren Gerben , Juneja Manisha , Pellegrino Christophe , Louhivuori Lauri , Bartesaghi Luca , Rochat Cylia , El Mansour Omar , Médard Jean-Jacques , Croisier Marie , Maclachlan Catherine , Poirot Olivier , Uhlén Per , Timmerman Vincent , Tricaud Nicolas , Schneider Bernard L. , Chrast Roman 
Published: January 2019

SignificanceInteractions between mitochondria and the endoplasmic reticulum (ER) at the level of mitochondria-associated membranes (MAM) constitute a key signaling hub, emerging as a shared target altered in multiple neurodegenerative diseases. We use both in vivo and in vitro models of Charcot–Marie–Tooth type 2A, an axonal form of neuropathy, to demonstrate that the presence of mutated Mitofusin 2 leads to altered MAM. In neurons, these modifications occur concomitantly with activation of ER stress response, dysregulated calcium handling, and alterations in mitochondrial morphology and transport, collectively contributing to axonopathy. Importantly, the reported results indicate that the pathological consequences of mutated Mitofusin 2 may be targeted with drugs reinforcing the ER–mitochondria cross-talk and/or reducing ER stress.
Liquid water is a dynamic polydisperse branched polymer
Authors: Naserifar Saber , Goddard William A. 
Published: January 2019

Significance
In contrast to ice, in which each water makes strong hydrogen bonds (SHBs) to four neighbors, we show that upon melting the number of SHBs drops quickly to two in liquid water. These two SHBs couple into chains containing ∼150 waters resembling a branched polymer. The lifetime of each SHB at 298 K is 90.3 fs (11 OH vibrational periods), so the polymer branches evolve dynamically. This dynamics-branched polymer paradigm may explain long-standing puzzles of water, such as the critical point at 227 K in supercooled water (which may correspond to a glass transition caused by an increase in the SHB lifetime). It may explain the observed angular correlations in water that persist for 20 nm.
Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma
Authors: Zhao Yanxia , Cao Jinghong , Melamed Alexander , Worley Michael , Gockley Allison , Jones Dennis , Nia Hadi T. , Zhang Yanling , Stylianopoulos Triantafyllos , Kumar Ashwin S. , Mpekris Fotios , Datta Meenal , Sun Yao , Wu Limeng , Gao Xing , Yeku Oladapo , del Carmen Marcela G. , Spriggs David R. , Jain Rakesh K. , Xu Lei 
Published: January 2019

Significance
Despite initial responsiveness to chemotherapy, the overwhelming majority of advanced ovarian cancer patients relapse with resistant disease. Thus, developing more effective strategies for ovarian cancer treatment is a high clinical priority. Here, we report that targeting angiotensin signaling with losartan, an angiotensin receptor blocker, can reduce extracellular matrix in ovarian tumors and the associated physical barriers that normally hinder drug delivery and efficacy. These changes in the tumor microenvironment lead to improved response to chemotherapy, and, importantly, decrease ascites—a major burden for ovarian cancer patients. These preclinical findings are in concert with our retrospective analysis showing improved survival in patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer and should be tested in a clinical trial.
Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma
Authors: Villanova Tania , Gesmundo Iacopo , Audrito Valentina , Vitale Nicoletta , Silvagno Francesca , Musuraca Chiara , Righi Luisella , Libener Roberta , Riganti Chiara , Bironzo Paolo , Deaglio Silvia , Papotti Mauro , Cai Renzhi , Sha Wei , Ghigo Ezio , Schally Andrew V. , Granata Riccarda 
Published: January 2019

Significance
Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis and limited treatment options. MPM remains a serious public health problem, and novel therapeutic strategies are urgently needed. The antitumor properties of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different cancers; however, their influence in MPM remains unexplored. Our work shows that GHRH antagonists MIA-602 and MIA-690 reduce survival, proliferation, and migration of human MPM cell lines and primary MPM cells in vitro by modulating apoptotic and oncogenic pathways. In vivo, GHRH antagonists inhibited the growth of MPM xenografts and blunted the production of growth factors in tumors. Overall, the inhibitory activities described in this study suggest that GHRH antagonists may be considered for development of therapies for MPM.
Australian schools as deliberative spaces: framing the goal of active and informed citizenship
Authors: Sorial Sarah , Peterson Andrew 
Published: January 2019

AbstractEducating for active and informed citizenship represents a core goal of Australian education and schooling. Owing to a range of factors – including the contested conceptual nature of citizenship and democracy – there is reason to question the extent to which this goal is being translated into practice. Similarly, while the Australian Curriculum requires students to engage with others in talk, this is framed rather broadly. Recognizing the value of greater conceptual precision about citizenship, democracy and discursive interactions, this article explores the value of deliberative democracy as a frame for active and informed citizenship. In doing so it argues that viewing schools as deliberative spaces which do/could engage in deliberative pedagogies provides a useful and focused basis for conceiving how young Australians do and can engage in, and learn, the capacities necessary for democratic citizenship.
Hemorrhagic conversion after alteplase administration in a patient with vasculitis and acute ischemic stroke
Authors: Gilbert Brian W , Dhakal Laxmi , Lacy Alison , Huffman Joel B 
Published: January 2019

Abstract

Purpose
A case of alteplase administration to a patient with vasculitis and acute ischemic stroke (AIS) is reported.

Summary
A 38-year-old woman with a recent diagnosis of granulomatosis with polyangiitis (GPA) received alteplase for AIS and developed symptomatic hemorrhagic conversion. Published reports regarding the safety of thrombolytic therapy in patients with a high inflammatory burden are inconsistent. The current case adds to the literature on the topic.

Conclusion
More data regarding alteplase treatment in patients with GPA are needed to further establish the safety of this therapy.
Efficient implementation of convolutional neural networks in the data processing of two-photon in vivo imaging
Authors: Wang Yangzhen , Su Feng , Wang Shanshan , Yang Chaojuan , Tian Yonglu , Yuan Peijiang , Liu Xiaorong , Xiong Wei , Zhang Chen 
Published: January 2019

Abstract

Motivation
Functional imaging at single-neuron resolution offers a highly efficient tool for studying the functional connectomics in the brain. However, mainstream neuron-detection methods focus on either the morphologies or activities of neurons, which may lead to the extraction of incomplete information and which may heavily rely on the experience of the experimenters.

Results
We developed a convolutional neural networks and fluctuation method-based toolbox (ImageCN) to increase the processing power of calcium imaging data. To evaluate the performance of ImageCN, nine different imaging datasets were recorded from awake mouse brains. ImageCN demonstrated superior neuron-detection performance when compared with other algorithms. Furthermore, ImageCN does not require sophisticated training for users.

Availability and implementation
ImageCN is implemented in MATLAB. The source code and documentation are available at https://github.com/ZhangChenLab/ImageCN.

Supplementary information
Supplementary data are available at Bioinformatics online.
Best-first search guided multistage mass spectrometry-based glycan identification
Authors: Wang Yaojun , Bu Dongbo , Huang Chuncui , Wang Hui , Zhou Jinyu , Dong Junchuan , Pan Weiyi , Zhang Jingwei , Zhang Qi , Li Yan , Sun Shiwei 
Published: January 2019

Abstract

Motivation
Glycan identification has long been hampered by complicated branching patterns and various isomeric structures of glycans. Multistage mass spectrometry (MSn) is a promising glycan identification technique as it generates multiple-level fragments of a glycan, which can be explored to deduce branching pattern of the glycan and further distinguish it from other candidates with identical mass. However, the automatic glycan identification still remains a challenge since it mainly relies on expertise to guide a MSn instrument to generate spectra.

Results
Here, we proposed a novel method, named bestFSA, based on a best-first search algorithm to guide the process of spectrum producing in glycan identification using MSn. BestFSA is able to select the most appropriate peaks for next round of experiments and complete the identification using as few experimental rounds. Our analysis of seven representative glycans shows that bestFSA correctly distinguishes actual glycans efficiently and suggested bestFSA could be used in practical glycan identification. The combination of the MSn technology coupled with bestFSA should greatly facilitate the automatic identification of glycan branching patterns, with significantly improved identification sensitivity, and reduce time and cost of MSn experiments.

Availability and implementation
http://glycan.ict.ac.cn

Supplementary information
Supplementary data are available at Bioinformatics online.
How can we make renal medicine careers more appealing to UK trainees?
Authors: Karangizi Alvin H K , Chanouzas Dimitrios , Mahdi Amar , Foggensteiner Lukas 
Published: January 2019

Abstract

Background
There is a global decline in interest in careers in renal medicine. This is concerning given the increasing global burden of kidney disease. Previous studies in the USA and Australia have identified factors such as a poor work–life balance, lack of role models and the challenging nature of the speciality as possible reasons behind recruitment struggles. This study aimed to identify factors associated with declining interest among trainees in the UK.

Methods
We conducted a survey of 150 National Health Service Foundation trainees (interns) and Core Medical Trainees in Health Education West Midlands. Participants completed a 14-part paper-based questionnaire capturing data on trainee demographics, medical school and postgraduate exposure to renal medicine and perceptions of a career in renal medicine.

Results
There was limited early clinical exposure to renal medicine both in terms of time spent in the speciality and perceived exposure to the range of domains of the speciality. Trainees perceived the speciality as complex with a heavy workload. Very few trainees considered the speciality to be lifestyle oriented. There was also disinterest in taking on the associated general medicine commitments of the training programme. Job experience and identification of role models increased the likelihood of consideration of the speciality.

Conclusion
This survey has identified key areas to drive interest in the speciality, including early engagement, enthusiastic supervision and increased training flexibility. Urgent attention is required to address these areas and make renal medicine careers more appealing.
Perioperative management of adult cadaveric and live donor renal transplantation in the UK: a survey of national practice
Authors: Morkane Clare M , Fabes Jez , Banga Neal R , Berry Peter D , Kirwan Christopher J 
Published: January 2019

AbstractBackgroundThere is a limited evidence base and no national consensus regarding the perioperative management of patients undergoing renal transplantation. We developed an electronic survey to capture an overview of renal transplant perioperative practice across UK renal transplant centres and determine the need for future guidelines on patient management.MethodsA 29-question survey was developed to encompass the entire renal transplant perioperative pathway and input was sought from clinicians with expertise in renal transplant surgery, anaesthesia, nephrology and intensive care. The survey was sent to lead renal anaesthetists at each of the 23 transplant centres across the UK.ResultsA 96% response rate was achieved with 22 out of 23 centres returning complete responses. There was limited evidence of guideline-based approaches to preoperative workup. Questions regarding intraoperative fluid management, blood pressure targets, vasopressor administration and central venous pressure (CVP) monitoring identified a broad range of practice. Of note, the routine use of goal-directed fluid therapy based on cardiac output estimation was reported in six (27.3%) centres, while nine centres (40.9%) continue to target a specific CVP intraoperatively. In all, 12 (54.5%) centres perform transversus abdominis plane blocks with fentanyl-based patient-controlled analgesia as the most common mode of postoperative analgesia. A single centre reported a renal transplant-specific Enhanced Recovery after Surgery programme for cadaveric organ recipients.ConclusionsThis questionnaire highlighted a high degree of heterogeneity in current UK practice as regards the perioperative management of renal transplant recipients. Development of evidence-based national consensus guidelines to standardize the perioperative care of these patients is recommended in order to improve patient outcomes and focus areas of future research.
Anthropocene Feminism, Companion Species, and the MaddAddam Trilogy
Authors: Jennings Hope 
Published: January 2019

AbstractThis article claims that Margaret Atwood’s MaddAddam trilogy (2003–2013) offers insights into an emerging “anthropocene feminism” that disrupts the universalized “human” asserted by the Anthropocene. Likewise, Atwood decolonizes Anthropocene discourses by critiquing their reliance on human exceptionalism. By contrasting male characters who adopt humanist–imperialist perspectives with the character of Toby, whose evolving relations with nonhumans are aligned with a feminist new materialist vision, Atwood develops a compelling politics of the posthuman. The trilogy’s privileging of hybrid ontologies reveals the mutually entangled relations that exist between companion species. Arguing for a posthuman ethics, Atwood challenges the Anthropocene’s apocalyptic determinisms and suggests that only such an ethics makes possible a world that continues rather than ends.