bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dignity-conserving care for persons with palliative care needs — identifying outcomes studied in research: An integrative review
Authors: Söderman Annika , Östlund Ulrika , Werkander Harstäde Carina , Blomberg Karin 
Published: March 2020

AbstractObjectivesWith people living longer, palliative care may be required for lengthier periods of time. This puts demands on healthcare organizations to provide optimal palliative care. Maintaining dignity is central for any person's health and quality of life, but especially for a person with palliative care needs. Dignity-conserving care needs to be evaluated to increase knowledge about outcomes and how to assess these. The purpose of this integrative review was to identify outcomes studied within dignity-conserving care and how these have been operationalized.MethodsAn integrative review was conducted in 26 quantitative or mixed-method studies and study protocols. Thematic synthesis with an abductive approach was used for analysis.ResultsSeven themes of studied outcomes were identified, as well as four cluster themes: themes related to Illness-Related Concerns, themes related to the Dignity-Conserving Repertoire, themes related to the Social Dignity Inventory, and themes regarding Overarching Dignity Issues. Most outcomes studied dealt with Illness-Related Concerns within the themes of “Performance, symptoms and emotional concerns” and “End-of-life and existential aspects”. Themes linked to the Social Dignity Inventory had the lowest number of outcomes studied. Outcomes regarding overarching dignity issues such as “Dignity-related distress” and “Quality of life” were common. However, the results lacked concrete communication outcomes.Significance of resultsThe results will underpin future research in which dignity-conserving care is implemented and evaluated, and contribute to the provision of evidence-based palliative care. A greater focus on outcomes within cluster themes related to the Dignity-Conserving Repertoire and the Social Dignity Inventory is needed, as is more focus on communication outcomes.
Submesoscale Fronts in the Antarctic Marginal Ice Zone and Their Response to Wind Forcing
Authors: Swart Sebastiaan , du Plessis Marcel D. , Thompson Andrew F. , Biddle Louise C. , Giddy Isabelle , Linders Torsten , Mohrmann Martin , Nicholson Sarah‐Anne 
Published: March 2020

AbstractSubmesoscale flows in the ocean are energetic motions, O(1–10 km), that influence stratification and the distributions of properties, such as heat and carbon. They are believed to play an important role in sea‐ice‐impacted oceans by modulating air‐sea‐ice fluxes and sea‐ice extent. The intensity of these flows and their response to wind forcing are unobserved in the sea‐ice regions of the Southern Ocean. We present the first submesoscale‐resolving observations in the Antarctic marginal ice zone (MIZ) collected by surface and underwater autonomous vehicles, for >3 months in austral summer. We observe salinity‐dominated lateral density fronts occurring at sub‐kilometer scales. Surface winds are shown to modify the magnitude of the mixed‐layer density fronts, revealing strongly coupled atmosphere‐ocean processes. We posture that these wind‐front interactions occur as a continuous interplay between front slumping and vertical mixing, which leads to the dispersion of submesoscale fronts. Such processes are expected to be ubiquitous in the Southern Ocean MIZ.
Warning Time Analysis From SEP Simulations of a Two‐Tier REleASE System Applied to Mars Exploration
Authors: Posner A. , Strauss R.D. 
Published: March 2020

AbstractThe sudden exposure to energetic protons from solar energetic particle (SEP) events beyond the Earth's magnetosphere and en route to and from Mars can, in extreme cases, lead to acute radiation sickness, an impairing, mission‐endangering condition for astronauts. Timely warnings of their impending occurrence may significantly reduce radiation exposure by allowing astronauts sufficient time to move to a radiation shelter. The Relativistic Electron Alert System for Exploration (REleASE) has been developed to provide such early warnings for the Earth‐Moon system by exploiting the time difference of the arrival of SEP electrons and ions at 1 AU. This study explores the effectiveness of REleASE in a scenario that assumes a two‐element system, one placed at Earth‐Sun L1 and the other at Mars‐Sun L1. This system would exploit the Hohmann‐Parker effect, the circumstance that a spacecraft remains close to the heliospheric magnetic field lines that connect Earth and/or Mars with the Sun while in the Hohmann transfer orbit. We investigate whether the two‐element REleASE system would provide advance warnings for all phases of a mission to and from Mars. In the absence of adequate long‐term SEP measurements beyond Earth orbit, we employ 2‐D modeling of SEP injection and transport for SEP exposure scenarios, in which the best magnetic connections and thus most rapid flux increases of protons occur at exploration vehicle. We show the relative timing of alert occurrence and arrival of harmful ions at the spacecraft throughout a round‐trip human mission to Mars.
Comments on “A Modified Particle Filter‐Based Data Assimilation Method for a High‐Precision 2‐D Hydrodynamic Model Considering Spatial‐Temporal Variability of Roughness: Simulation of Dam‐Break Flood Inundation” by Cao et al.
Authors: Qin Jie , Wu Teng 
Published: March 2020

AbstractCao et al. (2019, https://doi.org/10.1029/2018WR023568) proposed a modified particle filter‐based data assimilation method with a local weighting procedure (MPFDA‐LW) for a two‐dimensional hydrodynamic model (HydroM2D) in dam‐break flood simulation. The MPFDA‐LW method intends to take into account the spatial‐temporal variability of the Manning coefficient to improve the performances of the HydroM2D model. Although Cao et al. (2019, https://doi.org/10.1029/2018WR023568) correctly pointed out that the Manning coefficient may spatially and temporally vary during a flooding process, the approach they handled this issue was inappropriate because they arbitrarily adjusted model parameters without considering the physical mechanism behind them. In addition, contrary to what the authors claimed, the proposed MPFDA‐LW method can barely improve the prediction of flooding processes, because changing the Manning coefficient at several computational grid cells has little influence on the overall flooding processes.
The 3‐D Facies and Geomechanical Modeling of Land Subsidence in the Chaobai Plain, Beijing
Authors: Zhu Lin , Franceschini Andrea , Gong Huili , Ferronato Massimiliano , Dai Zhenxue , Ke Yinghai , Pan Yun , Li Xiaojuan , Wang Rong , Teatini Pietro 
Published: March 2020

AbstractThe hydrogeologic systems of alluvial fan are characterized by a heterogeneous distribution of various lithological units/facies. The structure (integral scale and volumetric proportion) of the hydrofacies distribution and the values of the hydrogeomechanical parameters of each facies can play a major role on the system response to groundwater withdrawal in term of land subsidence. We propose a novel approach where stochastically simulated hydrofacies distributions are coupled with 3‐D finite element groundwater flow and geomechanical simulations to characterize land subsidence and horizontal movements due to groundwater withdrawal under a statistical framework. The integrated approach is applied on the Chaobai alluvial plain, China, an area of about 1,100 km2 where the main wellfields supplying water to Beijing are located. Groundwater pumping from the 1960s to now caused a land subsidence larger than 1 m and the present subsidence rate peaks to 70 mm/year. A Monte Carlo simulation with 100 hydrofacies generations is used. The model outcomes highlight how the heterogeneous structure of the hydrofacies fan reflects into the computed displacement fields. The standard deviation associated to the mean displacement field amounts up to 1/10 of the displacement components. The larger coefficient of variation (CV up to 0.5) is associated to the zone characterized by longer integral scale and with localized groundwater withdrawals. The computed variability of the subsidence rate, in the range of 1 to 3 mm/year, reflecting the intrinsic heterogeneous nature of an alluvial fan, corresponds to the short‐distance variability of land subsidence measured by persistent scatterer interferometry.
Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases
Authors: De Piano Mario , Manuelli Valeria , Zadra Giorgia , Otte Jonathan , Edqvist Per-Henrik D. , Pontén Fredrik , Nowinski Salpie , Niaouris Athanasios , Grigoriadis Anita , Loda Massimo , Van Hemelrijck Mieke , Wells Claire M. 
Published: March 2020

AbstractFatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.
ZBP1 (DAI/DLM-1) promotes osteogenic differentiation while inhibiting adipogenic differentiation in mesenchymal stem cells through a positive feedback loop of Wnt/β-catenin signaling
Authors: Zhao Xuefeng , Xie Liang , Wang Zhiyong , Wang Jiongke , Xu Hao , Han Xianglong , Bai Ding , Deng Peng 
Published: March 2020

AbstractThe lineage specification of mesenchymal stem/stromal cells (MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1 (also known as DAI or DLM-1) have been reported in the blood circulation and immune systems. However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs (mBMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted mBMSCs was restored at both the molecular and phenotypic levels. Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.
Big data in digital healthcare: lessons learnt and recommendations for general practice
Authors: Agrawal Raag , Prabakaran Sudhakaran 
Published: March 2020

AbstractBig Data will be an integral part of the next generation of technological developments—allowing us to gain new insights from the vast quantities of data being produced by modern life. There is significant potential for the application of Big Data to healthcare, but there are still some impediments to overcome, such as fragmentation, high costs, and questions around data ownership. Envisioning a future role for Big Data within the digital healthcare context means balancing the benefits of improving patient outcomes with the potential pitfalls of increasing physician burnout due to poor implementation leading to added complexity. Oncology, the field where Big Data collection and utilization got a heard start with programs like TCGA and the Cancer Moon Shot, provides an instructive example as we see different perspectives provided by the United States (US), the United Kingdom (UK) and other nations in the implementation of Big Data in patient care with regards to their centralization and regulatory approach to data. By drawing upon global approaches, we propose recommendations for guidelines and regulations of data use in healthcare centering on the creation of a unique global patient ID that can integrate data from a variety of healthcare providers. In addition, we expand upon the topic by discussing potential pitfalls to Big Data such as the lack of diversity in Big Data research, and the security and transparency risks posed by machine learning algorithms.
Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina
Authors: Park Tea Soon , Zimmerlin Ludovic , Evans-Moses Rebecca , Thomas Justin , Huo Jeffrey S. , Kanherkar Riya , He Alice , Ruzgar Nensi , Grebe Rhonda , Bhutto Imran , Barbato Michael , Koldobskiy Michael A. , Lutty Gerard , Zambidis Elias T. 
Published: March 2020

AbstractHere, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human naïve epiblast-like pluripotent state. Naïve diabetic vascular progenitors (N-DVP) differentiated from patient-specific naïve diabetic hiPSC (N-DhiPSC) possessed higher vascular functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, and were more efficient in migrating to and re-vascularizing the deep neural layers of the ischemic retina than isogenic diabetic vascular progenitors (DVP). These findings suggest that reprogramming to a stable naïve human pluripotent stem cell state may effectively erase dysfunctional epigenetic donor cell memory or disease-associated aberrations in patient-specific hiPSC. More broadly, tankyrase inhibitor-regulated naïve hiPSC (N-hiPSC) represent a class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.
Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation
Authors: Ji Qing , Zhou Lihong , Sui Hua , Yang Liu , Wu Xinnan , Song Qing , Jia Ru , Li Ruixiao , Sun Jian , Wang Ziyuan , Liu Ningning , Feng Yuanyuan , Sun Xiaoting , Cai Gang , Feng Yu , Cai Jianfeng , Cao Yihai , Cai Guoxiang , Wang Yan , Li Qi 
Published: March 2020

AbstractTumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor–stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.
Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants
Authors: Shu Xiang , Long Jirong , Cai Qiuyin , Kweon Sun-Seog , Choi Ji-Yeob , Kubo Michiaki , Park Sue K. , Bolla Manjeet K. , Dennis Joe , Wang Qin , Yang Yaohua , Shi Jiajun , Guo Xingyi , Li Bingshan , Tao Ran , Aronson Kristan J. , Chan Kelvin Y. K. , Chan Tsun L. , Gao Yu-Tang , Hartman Mikael , Kee Ho Weang , Ito Hidemi , Iwasaki Motoki , Iwata Hiroji , John Esther M. , Kasuga Yoshio , Soon Khoo Ui , Kim Mi-Kyung , Kong Sun-Young , Kurian Allison W. , Kwong Ava , Lee Eun-Sook , Li Jingmei , Lophatananon Artitaya , Low Siew-Kee , Mariapun Shivaani , Matsuda Koichi , Matsuo Keitaro , Muir Kenneth , Noh Dong-Young , Park Boyoung , Park Min-Ho , Shen Chen-Yang , Shin Min-Ho , Spinelli John J. , Takahashi Atsushi , Tseng Chiuchen , Tsugane Shoichiro , Wu Anna H. , Xiang Yong-Bing , Yamaji Taiki , Zheng Ying , Milne Roger L. , Dunning Alison M. , Pharoah Paul D. P. , García-Closas Montserrat , Teo Soo-Hwang , Shu Xiao-ou , Kang Daehee , Easton Douglas F. , Simard Jacques , Zheng Wei 
Published: March 2020

AbstractKnown risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
Dominant resistance and negative epistasis can limit the co-selection of de novo resistance mutations and antibiotic resistance genes
Authors: Porse Andreas , Jahn Leonie J. , Ellabaan Mostafa M. H. , Sommer Morten O. A. 
Published: March 2020

AbstractTo tackle the global antibiotic resistance crisis, antibiotic resistance acquired either vertically by chromosomal mutations or horizontally through antibiotic resistance genes (ARGs) have been studied. Yet, little is known about the interactions between the two, which may impact the evolution of antibiotic resistance. Here, we develop a multiplexed barcoded approach to assess the fitness of 144 mutant-ARG combinations in Escherichia coli subjected to eight different antibiotics at 11 different concentrations. While most interactions are neutral, we identify significant interactions for 12% of the mutant-ARG combinations. The ability of most ARGs to confer high-level resistance at a low fitness cost shields the selective dynamics of mutants at low drug concentrations. Therefore, high-fitness mutants are often selected regardless of their resistance level. Finally, we identify strong negative epistasis between two unrelated resistance mechanisms: the tetA tetracycline resistance gene and loss-of-function nuo mutations involved in aminoglycoside tolerance. Our study highlights important constraints that may allow better prediction and control of antibiotic resistance evolution.
Male sex is associated with aggressive behaviour and poor prognosis in Chinese papillary thyroid carcinoma
Authors: Ding Jinhua , Wu Weizhu , Fang Jianjiang , Zhao Jing , Jiang Li 
Published: March 2020

AbstractThe differences in prognosis of papillary thyroid carcinoma (PTC) by sex have been investigated in several previous studies, but the results have not been consistent. In addition, the impact of sex on the clinical and pathological characteristics, especially on central lymph node metastasis (CLNM), still remains unknown. To the best of our knowledge, the impact of sex on PTC has not been investigated in the Chinese PTC population. Therefore, our study retrospectively analysed the data of 1339 patients who were diagnosed with PTC and had received radical surgery at Ningbo Medical Center, Lihuili Hospital. In addition to cancer-specific death, structural recurrence and risk stratification, prognosis was also estimated by using three conventional prognostic systems: AMES (age, distant metastasis, extent, size), MACIS (distant metastasis, age, completeness of resection, local invasion, size) and the 8th version TNM (tumor, lymph node, metastasis) staging system. The clinical and pathological characteristics and above prognostic indexes were compared between male and female PTC patients. The results showed that there were higher rates of non-microcarcinoma PTC (nM-PTC), CLNM, lateral lymph node metastasis (LLNM), advanced disease and bilateral disease, but there was a lower rate of concurrent Hashimoto’s thyroiditis (HT) in male PTC patients than in female PTC patients. Additionally, the rate of intermediate-risk, high-risk or advanced disease was higher in male PTC patients. The above findings indicate that PTC in men is a more aggressive disease and may have a worse prognosis; thus, it should be treated with more caution.
Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing
Authors: Shin Jung U , Abaci Hasan E. , Herron Lauren , Guo Zongyou , Sallee Brigitte , Pappalardo Alberto , Jackow Joanna , Wang Eddy Hsi Chun , Doucet Yanne , Christiano Angela M. 
Published: March 2020

AbstractDrug screening studies for inflammatory skin diseases are currently performed using model systems that only partially recapitulate human diseased skin. Here, we developed a new strategy to incorporate T cells into human 3D skin constructs (HSCs), which enabled us to closely monitor and quantitate T cell responses. We found that the epidermis promotes the activation and infiltration of T cells into the skin, and provides a directional cue for their selective migration towards the epidermis. We established a psoriatic HSC (pHSC) by incorporating polarized Th1/Th17 cells or CCR6+CLA+ T cells derived from psoriasis patients into the constructs. These pHSCs showed a psoriatic epidermal phenotype and characteristic cytokine profiles, and responded to various classes of psoriasis drugs, highlighting the potential utility of our model as a drug screening platform. Taken together, we developed an advanced immunocompetent 3D skin model to investigate epidermal-T cell interactions and to understand the pathophysiology of inflammatory skin diseases in a human-relevant and patient-specific context.