bluuebunny/crossref_metadata_2025_split huggingface dataset:
Path to net zero is critical to climate outcome
Authors: Sun Tianyi , Ocko Ilissa B. , Sturcken Elizabeth , Hamburg Steven P. 
Published: November 2021

AbstractNet zero greenhouse gas targets have become a central element for climate action. However, most company and government pledges focus on the year that net zero is reached, with limited awareness of how critical the emissions pathway is in determining the climate outcome in both the near- and long-term. Here we show that different pathways of carbon dioxide and methane—the most prominent long-lived and short-lived greenhouse gases, respectively—can lead to nearly 0.4 °C of warming difference in midcentury and potential overshoot of the 2 °C target, even if they technically reach global net zero greenhouse gas emissions in 2050. While all paths achieve the Paris Agreement temperature goals in the long-term, there is still a 0.2 °C difference by end-of-century. We find that early action to reduce both emissions of carbon dioxide and methane simultaneously leads to the best climate outcomes over all timescales. We therefore recommend that companies and countries supplement net zero targets with a two-basket set of interim milestones to ensure that early action is taken for both carbon dioxide and methane. A one-basket approach, such as the standard format for Nationally Determined Contributions, is not sufficient because it can lead to a delay in methane mitigation.
Factors associated with unplanned readmissions and costs following resection of brain metastases in the United States
Authors: Tonse Raees , Townsend Alexandra , Rubens Muni , Siomin Vitaly , McDermott Michael W. , Tom Martin C. , Hall Matthew D. , Odia Yazmin , Ahluwalia Manmeet S. , Mehta Minesh P. , Kotecha Rupesh 
Published: November 2021

AbstractThe purpose of this study was to critically analyze the risk of unplanned readmission following resection of brain metastasis and to identify key risk factors to allow for early intervention strategies in high-risk patients. We analyzed data from the Nationwide Readmissions Database (NRD) from 2010–2014, and included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rate. Secondary outcomes included reasons and costs of readmissions. Hierarchical logistic regression model was used to identify the factors associated with 30-day readmission following craniotomy for brain metastasis. During the study period, 44,846 index hospitalizations occurred for patients who underwent resection of brain metastasis. In this cohort, 17.8% (n = 7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the five-year study period (p-trend = 0.286). The median per-patient cost for 30-day unplanned readmission was $11,109 and this amounted to a total of $26.4 million per year, which extrapolates to a national expenditure of $269.6 million. Increasing age, male sex, insurance status, Elixhauser comorbidity index, length of stay, teaching status of the hospital, neurological complications and infectious complications were associated with 30-day readmission following discharge after an index admission for craniotomy for brain metastasis. Unplanned readmission rates after resection of brain metastasis remain high and involve substantial healthcare expenditures. Developing tools and interventions to prevent avoidable readmissions could focus on the high-risk patients as a future strategy to decrease substantial healthcare expense.
The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking
Authors: Sehl Olivia C. , Foster Paula J. 
Published: November 2021

AbstractMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells. Cells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. Using the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 × 1016 19F atoms) were detected with 19F MRI, with SNR > 5. MPI has the potential to be more sensitive than 19F MRI for cell tracking. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.
High species richness of tachinid parasitoids (Diptera: Calyptratae) sampled with a Malaise trap in Baihua Mountain Reserve, Beijing, China
Authors: Pei Wenya , Yan Liping , Pape Thomas , Wang Qike , Zhang Chuntian , Yang Nan , Du Fuxin , Zhang Dong 
Published: November 2021

AbstractTachinidae are one of the most speciose families of Diptera and the largest group of non-hymenopteran parasitoids. Little is known about their diversity, distribution patterns, and seasonal variation in most ecosystems. This study reports on tachinid flies collected by a Malaise trap over 73 weeks in Baihua Mountain Reserve, northern China, and investigates the patterns of local species richness and its temporal distribution. The most species-rich season was summer, but the majority of specimens were recovered in spring. A total of 755 tachinid specimens were collected, consisting of 144 species in 85 genera, comprising 26.5% of the species and 49.7% of the genera recorded from northern China. A total species richness of 243 was estimated, indicating that only a portion of the community of tachinid flies was collected at this location and suggesting that the diversity of tachinids might be underestimated across Beijing and northern China. This work is a first step in assessing patterns of tachinid diversity in China using quantitative sampling and establishes a baseline for comprehending the temporal and spatial diversity of these ecologically significant parasitoids.
Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells
Authors: Caohuy Hung , Eidelman Ofer , Chen Tinghua , Liu Shufeng , Yang Qingfeng , Bera Alakesh , Walton Nathan I. , Wang Tony T. , Pollard Harvey B. 
Published: November 2021

AbstractTo initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding. Here we report that ouabain, digitoxin, and digoxin, as well as sugar-free derivatives digitoxigenin and digoxigenin, are high-affinity competitive inhibitors of ACE2 binding to the Original [D614] S1 and the α/β/γ [D614G] S1 proteins. These drugs also inhibit ACE2 binding to the Original RBD, as well as to RBD proteins containing the β [E484K], Mink [Y453F] and α/β/γ [N501Y] mutations. As hypothesized, we also found that ouabain, digitoxin and digoxin blocked penetration by SARS-CoV-2 Spike-pseudotyped virus into human lung cells, and infectivity by native SARS-CoV-2. These data indicate that cardiac glycosides may block viral penetration into the target cell by first inhibiting ACE2:RBD binding. Clinical concentrations of ouabain and digitoxin are relatively safe for short term use for subjects with normal hearts. It has therefore not escaped our attention that these common cardiac medications could be deployed worldwide as inexpensive repurposed drugs for anti-COVID-19 therapy.
Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Køster Ditte , Egedal Johanne Hovgaard , Lomholt Søren , Hvid Malene , Jakobsen Martin R. , Müller-Ladner Ulf , Eibel Hermann , Deleuran Bent , Kragstrup Tue Wenzel , Neumann Elena , Nielsen Morten Aagaard 
Published: November 2021

AbstractFibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.
The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction
Authors: Crisóstomo Verónica , Baéz-Diaz Claudia , Blanco-Blázquez Virginia , Álvarez Verónica , López-Nieto Esther , Maestre Juan , Bayes-Genis Antoni , Gálvez-Montón Carolina , Casado Javier G. , Sánchez-Margallo Francisco M. 
Published: November 2021

AbstractThe epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of cardiosphere-derived cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72 h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 min. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.
11C-acetate positron emission tomography is more precise than 18F-fluorodeoxyglucose positron emission tomography in evaluating tumor burden and predicting disease risk of multiple myeloma
Authors: Chen Miao , Zhu Wenjia , Du Jianhua , Yang Chen , Han Bing , Zhou Daobin , Huo Li , Zhuang Junling 
Published: November 2021

AbstractThe optimal method of tumor burden evaluation in newly diagnosed multiple myeloma (NDMM) is yet to be determined. This study aimed to compare the value of11C-acetate positron-emission tomography (PET)/computed tomography (CT) (AC-PET and18F-fluorodeoxyglucose PET/CT (FDG-PET) in the assessment of tumor burden in NDMM. This study evaluated 64 NDMM patients between February 2015 and July 2018. AC-PET and FDG-PET were used to assess myeloma lesions. The clinical data, imaging results, and their correlations were analyzed. Diffuse bone marrow uptake in AC-PET was significantly correlated with biomarkers for tumor burden, including serum hemoglobin (P = 0.020), M protein (P = 0.054), the percentage of bone marrow plasma cells (P < 0.001), and the Durie–Salmon stage of the disease (P = 0.007). The maximum standard uptake value (SUVmax) of focal lesions and high diffuse bone marrow uptake in AC-PET showed stronger correlations with high-risk disease (P = 0.017,P = 0.013) than those in FDG-PET. Moreover, the presence of diffuse bone marrow uptake, more than ten focal lesions, and an SUVmaxof focal lesions of > 6.0 in AC-PET, but not in FDG-PET, predicted a higher probability of disease progression and shorter progression-free survival (P < 0.05). AC-PET outperformed FDG-PET in tumor burden evaluation and disease progression prediction in NDMM.
Electrode montage-dependent intracranial variability in electric fields induced by cerebellar transcranial direct current stimulation
Authors: Klaus Jana , Schutter Dennis J. L. G. 
Published: November 2021

AbstractTranscranial direct current stimulation (tDCS) is an increasingly popular tool to investigate the involvement of the cerebellum in a variety of brain functions and pathologies. However, heterogeneity and small effect sizes remain a common issue. One potential cause may be interindividual variability of the electric fields induced by tDCS. Here, we compared electric field distributions and directions between two conventionally used electrode montages (i.e., one placing the return electrode over the ipsilateral buccinator muscle and one placing the return electrode [25 and 35 cm2 surface area, respectively] over the contralateral supraorbital area; Experiment 1) and six alternative montages (electrode size: 9 cm2; Experiment 2) targeting the right posterior cerebellar hemisphere at 2 mA. Interindividual and montage differences in the achieved maximum field strength, focality, and direction of current flow were evaluated in 20 head models and the effects of individual differences in scalp–cortex distance were examined. Results showed that while maximum field strength was comparable for all montages, focality was substantially improved for the alternative montages over inferior occipital positions. Our findings suggest that compared to several conventional montages extracerebellar electric fields are significantly reduced by placing smaller electrodes in closer vicinity of the targeted area.
Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1
Authors: Rathnasinghe Raveen , Salvatore Mirella , Zheng Hongyong , Jangra Sonia , Kehrer Thomas , Mena Ignacio , Schotsaert Michael , Muster Thomas , Palese Peter , García-Sastre Adolfo 
Published: November 2021

AbstractThe influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.
Mobile devices and wearable technology for measuring patient outcomes after surgery: a systematic review
Authors: Knight Stephen R. , Ng Nathan , Tsanas Athanasios , Mclean Kenneth , Pagliari Claudia , Harrison Ewen M. 
Published: November 2021

AbstractComplications following surgery are common and frequently occur the following discharge. Mobile and wearable digital health interventions (DHI) provide an opportunity to monitor and support patients during their postoperative recovery. Lack of high-quality evidence is often cited as a barrier to DHI implementation. This review captures and appraises the current use, evidence base and reporting quality of mobile and wearable DHI following surgery. Keyword searches were performed within Embase, Cochrane Library, Web of Science and WHO Global Index Medicus databases, together with clinical trial registries and Google scholar. Studies involving patients undergoing any surgery requiring skin incision where postoperative outcomes were measured using a DHI following hospital discharge were included, with DHI defined as mobile and wireless technologies for health to improve health system efficiency and health outcomes. Methodological reporting quality was determined using the validated mobile health evidence reporting and assessment (mERA) guidelines. Bias was assessed using the Cochrane Collaboration tool for randomised studies or MINORS depending on study type. Overall, 6969 articles were screened, with 44 articles included. The majority (n = 34) described small prospective study designs, with a high risk of bias demonstrated. Reporting standards were suboptimal across all domains, particularly in relation to data security, prior patient engagement and cost analysis. Despite the potential of DHI to improve postoperative patient care, current progress is severely restricted by limitations in methodological reporting. There is an urgent need to improve reporting for DHI following surgery to identify patient benefit, promote reproducibility and encourage sustainability.
Image-based high-throughput mapping of TGF-β-induced phosphocomplexes at a single-cell level
Authors: Lönn Peter , Al-Amin Rasel A. , Doulabi Ehsan Manouchehri , Heldin Johan , Gallini Radiosa , Björkesten Johan , Oelrich Johan , Kamali-Moghaddam Masood , Landegren Ulf 
Published: November 2021

AbstractProtein interactions and posttranslational modifications orchestrate cellular responses to e.g. cytokines and drugs, but it has been difficult to monitor these dynamic events in high-throughput. Here, we describe a semi-automated system for large-scale in situ proximity ligation assays (isPLA), combining isPLA in microtiter wells with automated microscopy and computer-based image analysis. Phosphorylations and interactions are digitally recorded along with subcellular morphological features. We investigated TGF-β-responsive Smad2 linker phosphorylations and complex formations over time and across millions of individual cells, and we relate these events to cell cycle progression and local cell crowding via measurements of DNA content and nuclear size of individual cells, and of their relative positions. We illustrate the suitability of this protocol to screen for drug effects using phosphatase inhibitors. Our approach expands the scope for image-based single cell analyses by combining observations of protein interactions and modifications with morphological details of individual cells at high throughput.
Large-scale integration of single-cell transcriptomic data captures transitional progenitor states in mouse skeletal muscle regeneration
Authors: McKellar David W. , Walter Lauren D. , Song Leo T. , Mantri Madhav , Wang Michael F. Z. , De Vlaminck Iwijn , Cosgrove Benjamin D. 
Published: November 2021

AbstractSkeletal muscle repair is driven by the coordinated self-renewal and fusion of myogenic stem and progenitor cells. Single-cell gene expression analyses of myogenesis have been hampered by the poor sampling of rare and transient cell states that are critical for muscle repair, and do not inform the spatial context that is important for myogenic differentiation. Here, we demonstrate how large-scale integration of single-cell and spatial transcriptomic data can overcome these limitations. We created a single-cell transcriptomic dataset of mouse skeletal muscle by integration, consensus annotation, and analysis of 23 newly collected scRNAseq datasets and 88 publicly available single-cell (scRNAseq) and single-nucleus (snRNAseq) RNA-sequencing datasets. The resulting dataset includes more than 365,000 cells and spans a wide range of ages, injury, and repair conditions. Together, these data enabled identification of the predominant cell types in skeletal muscle, and resolved cell subtypes, including endothelial subtypes distinguished by vessel-type of origin, fibro-adipogenic progenitors defined by functional roles, and many distinct immune populations. The representation of different experimental conditions and the depth of transcriptome coverage enabled robust profiling of sparsely expressed genes. We built a densely sampled transcriptomic model of myogenesis, from stem cell quiescence to myofiber maturation, and identified rare, transitional states of progenitor commitment and fusion that are poorly represented in individual datasets. We performed spatial RNA sequencing of mouse muscle at three time points after injury and used the integrated dataset as a reference to achieve a high-resolution, local deconvolution of cell subtypes. We also used the integrated dataset to explore ligand-receptor co-expression patterns and identify dynamic cell-cell interactions in muscle injury response. We provide a public web tool to enable interactive exploration and visualization of the data. Our work supports the utility of large-scale integration of single-cell transcriptomic data as a tool for biological discovery.
G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression
Authors: Cheng Jung-Chien , Fang Lanlan , Li Yuxi , Thakur Avinash , Hoodless Pamela A. , Guo Yanjie , Wang Zhen , Wu Ze , Yan Yang , Jia Qiongqiong , Gao Yibo , Han Xiaoyu , Yu Yiping , Sun Ying-Pu 
Published: November 2021

AbstractInsufficient invasion of trophoblast cells into the uterine decidua is associated with preeclampsia (PE). G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. GPER is expressed in human trophoblast cells and downregulated GPER levels are noted in PE. However, to date, the role of GPER in trophoblast cells remains largely unknown. Here, we applied RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to G1, an agonist of GPER, and identified angiopoietin-like 4 (ANGPTL4) as a target gene of GPER. Treatment of trophoblast cells with G1 or 17β-estradiol (E2) activated Yes-associated protein (YAP), the major downstream effector of the Hippo pathway, via GPER but in a mammalian STE20-like protein kinase 1 (MST1)-independent manner. Using pharmacological inhibitors as well as loss- and gain-of-function approaches, our results revealed that YAP activation was required for GPER-stimulated ANGPTL4 expression. Transwell invasion assays demonstrated that activation of GPER-induced ANGPTL4 promoted cell invasion. In addition, the expression levels of GPER, YAP, and ANGPTL4 were downregulated in the placenta of patients with PE. Our findings reveal a mechanism by which GPER exerts its stimulatory effect on human trophoblast cell invasion by upregulating YAP-mediated ANGPTL4 expression.