bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experts’ moral views on gene drive technologies: a qualitative interview study
Authors: de Graeff N. , Jongsma Karin R. , Bredenoord Annelien L. 
Published: March 2021

Abstract
Background
Gene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the academic literature.

Methods
In this qualitative study, we interviewed GDT experts (n = 33) from different disciplines to identify and better understand their moral views regarding these technologies. The pseudonymized transcripts were analyzed thematically.

Results
The respondents’ moral views were principally influenced by their attitudes towards (1) the uncertainty related to GDTs; (2) the alternatives to which they should be compared; and (3) the role humans should have in nature. Respondents agreed there is epistemic uncertainty related to GDTs, identified similar knowledge gaps, and stressed the importance of realistic expectations in discussions on GDTs. They disagreed about whether uncertainty provides a rationale to refrain from field trials (‘risks of intervention’ stance) or to proceed with phased testing to obtain more knowledge given the harms of the status quo (‘risks of non-intervention’ stance). With regards to alternatives to tackle vector-borne diseases, invasive species and agricultural pests, respondents disagreed about which alternatives should be considered (un)feasible and (in)sufficiently explored: conventional strategies (‘downstream solutions’ stance) or systematic changes to health care, political and agricultural systems (‘upstream solutions’ stance). Finally, respondents held different views on nature and whether the use of GDTs is compatible with humans’ role in nature (‘interference’ stance) or not (‘non-interference stance’).

Conclusions
This interview study helps to disentangle the debate on GDTs by providing a better understanding of the moral views of GDT experts. The obtained insights provide valuable stepping-stones for a constructive debate about underlying value conflicts and call attention to topics that deserve further (normative) reflection. Further evaluation of these issues can facilitate the debate on and responsible development of GDTs.
Combining structured and unstructured data in EMRs to create clinically-defined EMR-derived cohorts
Authors: Tam Charmaine S. , Gullick Janice , Saavedra Aldo , Vernon Stephen T. , Figtree Gemma A. , Chow Clara K. , Cretikos Michelle , Morris Richard W. , William Maged , Morris Jonathan , Brieger David 
Published: March 2021

AbstractBackgroundThere have been few studies describing how production EMR systems can be systematically queried to identify clinically-defined populations and limited studies utilising free-text in this process. The aim of this study is to provide a generalisable methodology for constructing clinically-defined EMR-derived patient cohorts using structured and unstructured data in EMRs.MethodsPatients with possible acute coronary syndrome (ACS) were used as an exemplar. Cardiologists defined clinical criteria for patients presenting with possible ACS. These were mapped to data tables within the production EMR system creating seven inclusion criteria comprised of structured data fields (orders and investigations, procedures, scanned electrocardiogram (ECG) images, and diagnostic codes) and unstructured clinical documentation. Data were extracted from two local health districts (LHD) in Sydney, Australia. Outcome measures included examination of the relative contribution of individual inclusion criteria to the identification of eligible encounters, comparisons between inclusion criterion and evaluation of consistency of data extracts across years and LHDs.ResultsAmong 802,742 encounters in a 5 year dataset (1/1/13–30/12/17), the presence of an ECG image (54.8% of encounters) and symptoms and keywords in clinical documentation (41.4–64.0%) were used most often to identify presentations of possible ACS. Orders and investigations (27.3%) and procedures (1.4%), were less often present for identified presentations. Relevant ICD-10/SNOMED CT codes were present for 3.7% of identified encounters. Similar trends were seen when the two LHDs were examined separately, and across years.ConclusionsClinically-defined EMR-derived cohorts combining structured and unstructured data during cohort identification is a necessary prerequisite for critical validation work required for development of real-time clinical decision support and learning health systems.
Molecular phylogenetics of a recently isolated goat pox virus from Vietnam
Authors: Pham Trang Hong , Rahaman Nor Yasmin Abdul , Lila Mohd Azmi Mohd , Lai Huong Lan Thi , Nguyen Lan Thi , Van Nguyen Giap , Ha Bo Xuan , Nguyen Hieu , Vu Hanh Duc , Noordin Mustapha M. 
Published: March 2021

Abstract
Background
After a decade of silence, an outbreak of the contagious and Asian endemic disease, goat pox re-emerged in North Vietnam affecting more than 1800 heads with a mortality rate of 6.5%. The inevitable impact of goat pox on hide quality, breeding, chevon and milk production has resulted in a significant economic losses to the developing goat industry of Vietnam. In the act of establishing an effective control of this devastating disease, tracing the source of re-emergence via a phylogenetic study was carried out to reveal their genetic relatedness. Either skin scab or papule from the six affected provinces were collected, cultured into Vero cells followed by restricted enzyme digestion of targeted P32 gene DNA encoding. The P32 gene was then cloned and transformed into E.coli competent cells for further sequencing.

Results
The isolated sequence is deposited into GenBank under Accession No. MN317561/VNUAGTP1. The phylogenetic tree revealed high similarity of nucleotide and amino acid sequences to references goat pox strains accounting for 99.6 and 99.3, respectively. The Vietnamese strain is clustered together with currently circulating goat pox virus in China, India and Pakistan which suggested the origin of South China.

Conclusions
This Vietnam isolate is clustered together with other Asian goat pox strains indicating the dissemination of a common goat pox virus within this continent.
CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma
Authors: Xu Shuwen , Li Xiaofeng , Li Longfei , Wang Yufeng , Geng Chong , Guo Feng , Zhang Tao , Du Aonan , Lu Zhiwei , Hui Hua , Wang Qiang 
Published: March 2021

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2′-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay.ResultsMiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter.ConclusionCTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.
Circ_DOCK1 regulates USP11 through miR-132-3p to control colorectal cancer progression
Authors: Zhang Weitong , Wang Zhenfen , Cai Guohao , Huang Ping 
Published: March 2021

AbstractBackgroundCircular RNAs (circRNAs) take part in colorectal cancer malignancies. CircRNA dedicator of cytokinesis 1 (circ_DOCK1) is involved in colorectal cancer progression, but the mechanism underlying this circRNA that takes part in colorectal cancer development remains largely undetermined.MethodsTumor and normal para-cancerous tissues were collected from 42 colorectal cancer patients. Human colorectal cancer cell lines (HCT116 and SW480) were used for the experiments in vitro. Circ_DOCK1, microRNA (miR)-132-3p, and ubiquitin-specific protease 11 (USP11) levels were measured through quantitative real-time polymerase chain reaction and Western blotting. Cell growth, metastasis, and apoptosis were investigated via colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, MTT, flow cytometry, Western blotting, and transwell analyses. The target association was evaluated via dual-luciferase reporter analysis, RNA pull-down, and immunoprecipitation (RIP). Xenograft assay was performed using HCT116 cells. USP11 and Ki67 levels in tumor tissues were detected via immunohistochemistry.ResultsCirc_DOCK1 expression was enhanced in colorectal cancer tissues and cells. Silencing circ_DOCK1 repressed cell growth, migration, and invasion, and facilitated apoptosis. Circ_DOCK1 sponged miR-132-3p, and miR-132-3p silence mitigated the effect of circ_DOCK1 interference on cell growth, metastasis, and apoptosis. MiR-132-3p targeted USP11, and circ_DOCK1 could regulate USP11 level by miR-132-3p. MiR-132-3p suppressed cell growth, metastasis, and apoptosis, and USP11 attenuated these effects. Knockdown of circ_DOCK1 decreased colorectal cancer cell xenograft tumor growth.ConclusionCirc_DOCK1 interference suppressed cell growth and metastasis, and increased apoptosis of colorectal cancer via decreasing USP11 by increasing miR-132-3p.
A random-sampling approach to track cell divisions in time-lapse fluorescence microscopy
Authors: Amarteifio Saoirse , Fallesen Todd , Pruessner Gunnar , Sena Giovanni 
Published: March 2021

AbstractBackgroundParticle-tracking in 3D is an indispensable computational tool to extract critical information on dynamical processes from raw time-lapse imaging. This is particularly true within vivotime-lapse fluorescence imaging in cell and developmental biology, where complex dynamics are observed at high temporal resolution. Common tracking algorithms used with time-lapse data in fluorescence microscopy typically assume a continuous signal where background, recognisable keypoints and independently moving objects of interest are permanently visible. Under these conditions, simple registration and identity management algorithms can track the objects of interest over time. In contrast, here we consider the case of transient signals and objects whose movements are constrained within a tissue, where standard algorithms fail to provide robust tracking.ResultsTo optimize 3D tracking in these conditions, we propose the merging of registration and tracking tasks into a registration algorithm that uses random sampling to solve the identity management problem. We describe the design and application of such an algorithm, illustrated in the domain of plant biology, and make it available as an open-source software implementation. The algorithm is tested on mitotic events in 4D data-sets obtained with light-sheet fluorescence microscopy on growingArabidopsis thalianaroots expressing CYCB::GFP. We validate the method by comparing the algorithm performance against both surrogate data and manual tracking.ConclusionThis method fills a gap in existing tracking techniques, following mitotic events in challenging data-sets using transient fluorescent markers in unregistered images.
Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation
Authors: Ito Takashi , Kakuuchi Midori , Maruyama Ikuro 
Published: March 2021

AbstractEndothelial cells play a key role in maintaining intravascular patency through their anticoagulant properties. They provide a favorable environment for plasma anticoagulant proteins, including antithrombin, tissue factor pathway inhibitor, and protein C. Under septic conditions, however, the anticoagulant properties of endothelial cells are compromised. Rather, activated/injured endothelial cells can provide a scaffold for intravascular coagulation. For example, the expression of tissue factor, an important initiator of the coagulation pathway, is induced on the surface of activated endothelial cells. Phosphatidylserine, a high-affinity scaffold for gamma-carboxyglutamate domain containing coagulation factors, including FII, FVII, FIX, and FX, is externalized to the outer leaflet of the plasma membrane of injured endothelial cells. Hemodilution decreases not only coagulation factors but also plasma anticoagulant proteins, resulting in unleashed activation of coagulation on the surface of activated/injured endothelial cells. The aberrant activation of coagulation can be suppressed in part by the supplementation of recombinant antithrombin and recombinant thrombomodulin. This review aims to overview the physiological and pathological functions of endothelial cells along with proof-of-concept in vitro studies. The pathophysiology of COVID-19-associated thrombosis is also discussed.
Effects of salvianolate on microcirculatory disturbance in patients with stable coronary heart disease: study protocol for a randomized controlled trial
Authors: Li Zhanlu , Luan Yi , Wang Min , Li Ya , Shen Xiaohua , Fu Guosheng , Zhang Wenbin 
Published: March 2021

Abstract
Background
Obstruction of coronary microcirculation can lead to myocardial ischemia and poor prognosis. Salvianolate exerts cardiovascular protection at cellular levels. However, no studies have confirmed the effect of salvianolate on stable coronary heart disease (CHD) with high fractional flow reserve (FFR) and myocardial microcirculatory disturbances.

Methods/design
This study will enroll 78 patients who have stable coronary disease with 50 to 70% stenosis in major coronary arteries and whose FFR > 0.80 and index of microcirculatory resistance (IMR) > 25. Patients will be randomly divided into the salvianolate group or the placebo group. After above evaluations, salvianolate 200 mg will be intravenously dripped immediately for the next 30 min and subsequent 7 days in the salvianolate group, and matching 0.9% normal saline will be arranged in the placebo group. IMR will be reevaluated in immediate phase after first 30 min of salvianolate or placebo treatment. The primary end point will be the IMR change in this phase, and the secondary end points will be the total ischemic burden assessed by the Seattle angina scale, quality of life scale, Holter electrocardiography, and 6-min walk test after 7 days before discharge.

Discussion
This study will firstly clarify the improvement effect of salvianolate on coronary microcirculation and provide an effective treatment method for stable CHD patients with high FFR and myocardial microcirculatory disturbance.

Trial registration
Chinese Clinical Trial Registry ChiCTR1800018772. Registered on 9 October 2018 and updated on 2 March 2020
A hidden cause of oxalate nephropathy: a case report
Authors: Mahmoud Tala , Ghandour Elias C. , Jaar Bernard G. 
Published: March 2021

Abstract
Background
Oxalate nephropathy is a rare disorder that can result in acute kidney injury (AKI) and progresses to end-stage kidney disease (ESKD). The causes can be either primary or secondary. Primary hyperoxaluria includes a group of hereditary disorders with enzymatic defects in the glyoxylate pathway, resulting in decreased oxalate metabolism. Secondary hyperoxaluria, often overlooked can result from increased intestinal absorption, nutritional deficiencies, decreased fluid intake, impaired excretion, and increased dietary consumption of oxalate.

Case presentation
We present a Caucasian case of acute oxalate induced nephropathy associated with consumption of large quantities of green vegetables in a patient with chronic kidney disease (CKD). Imaging study showed no evidence of kidney stone, but a kidney biopsy revealed acute tubular injury, tubular atrophy, interstitial fibrosis, and dense tubular deposition of calcium oxalate crystals. Upon further questioning the patient, we learned that in the months prior to presentation, he had very significantly increased his consumption of green vegetables. Because of no clinical improvement, the patient was initiated and maintained on hemodialysis.

Conclusion
This report illustrates a case of acute oxalate nephropathy in the setting of very high dietary consumption of oxalate-rich foods in a patient with advanced CKD. Special attention should be given to the secondary causes of hyperoxaluria in patients with predisposing conditions such as CKD.
Doorways do not always cause forgetting: a multimodal investigation
Authors: McFadyen Jessica , Nolan Christopher , Pinocy Ellen , Buteri David , Baumann Oliver 
Published: March 2021

Abstract
Background
The ‘doorway effect’, or ‘location updating effect’, claims that we tend to forget items of recent significance immediately after crossing a boundary. Previous research suggests that such a forgetting effect occurs both at physical boundaries (e.g., moving from one room to another via a door) and metaphysical boundaries (e.g., imagining traversing a doorway, or even when moving from one desktop window to another on a computer). Here, we aimed to conceptually replicate this effect using virtual and physical environments.

Methods
Across four experiments, we measured participants’ hit and false alarm rates to memory probes for items recently encountered either in the same or previous room. Experiments 1 and 2 used highly immersive virtual reality without and with working memory load (Experiments 1 and 2, respectively). Experiment 3 used passive video watching and Experiment 4 used active real-life movement. Data analysis was conducted using frequentist as well as Bayesian inference statistics.

Results
Across this series of experiments, we observed no significant effect of doorways on forgetting. In Experiment 2, however, signal detection was impaired when participants responded to probes after moving through doorways, such that false alarm rates were increased for mismatched recognition probes. Thus, under working memory load, memory was more susceptible to interference after moving through doorways.

Conclusions
This study presents evidence that is inconsistent with the location updating effect as it has previously been reported. Our findings call into question the generalisability and robustness of this effect to slight paradigm alterations and, indeed, what factors contributed to the effect observed in previous studies.
Neighborhood disadvantage and firearm injury: does shooting location matter?
Authors: Dalve Kimberly , Gause Emma , Mills Brianna , Floyd Anthony S. , Rivara Frederick P. , Rowhani-Rahbar Ali 
Published: March 2021

Abstract
Background
Firearm violence is a public health problem that disparately impacts areas of economic and social deprivation. Despite a growing literature on neighborhood characteristics and injury, few studies have examined the association between neighborhood disadvantage and fatal and nonfatal firearm assault using data on injury location. We conducted an ecological Bayesian spatial analysis examining neighborhood disadvantage as a social determinant of firearm injury in Seattle, Washington.

Methods
Neighborhood disadvantage was measured using the National Neighborhood Data Archive disadvantage index. The index includes proportion of female-headed households with children, proportion of households with public assistance income, proportion of people with income below poverty in the past 12 months, and proportion of the civilian labor force aged 16 and older that are unemployed at the census tract level. Firearm injury counts included individuals with a documented assault-related gunshot wound identified from medical records and supplemented with the Gun Violence Archive between March 20, 2016 and December 31, 2018. Available addresses were geocoded to identify their point locations and then aggregated to the census tract level. Besag-York-Mollie (BYM2) Bayesian Poisson models were fit to the data to estimate the association between the index of neighborhood disadvantage and firearm injury count with a population offset within each census tract.

Results
Neighborhood disadvantage was significantly associated with the count of firearm injury in both non-spatial and spatial models. For two census tracts that differed by 1 decile of neighborhood disadvantage, the number of firearm injuries was higher by 21.0% (95% credible interval: 10.5, 32.8%) in the group with higher neighborhood disadvantage. After accounting for spatial structure, there was still considerable residual spatial dependence with 53.3% (95% credible interval: 17.0, 87.3%) of the model variance being spatial. Additionally, we observed census tracts with higher disadvantage and lower count of firearm injury in communities with proximity to employment opportunities and targeted redevelopment, suggesting other contextual protective factors.

Conclusions
Even after adjusting for socioeconomic factors, firearm injury research should investigate spatial clustering as independence cannot be able to be assumed. Future research should continue to examine potential contextual and environmental neighborhood determinants that could impact firearm injuries in urban communities.
A pilot study of the impact of an exercise intervention on brain structure, cognition, and psychosocial symptoms in individuals with relapsing-remitting multiple sclerosis
Authors: Mayo Chantel D. , Harrison Laureen , Attwell-Pope Kristen , Stuart-Hill Lynneth , Gawryluk Jodie R. 
Published: March 2021

Abstract
Background
Despite pharmacological treatment, many individuals with multiple sclerosis (MS) continue to experience symptoms and medication side effects. Exercise holds promise for MS, but changes in brain structure following exercise have not been thoroughly investigated, and important cognitive and psychosocial variables are rarely primary outcomes. The aim of this pilot study was to investigate whether a 12-week exercise intervention would improve white matter integrity in the brain, or cognition, symptoms of fatigue, and depressed mood for individuals with relapsing-remitting MS (RRMS).

Method
Thirteen participants completed 12 weeks of speeded walking. Baseline and post-intervention testing included 3T diffusion tensor imaging (DTI) to assess white matter and neuropsychological testing to assess cognition, fatigue, and mood. Image pre-processing and analyses were performed in functional magnetic resonance imaging of the Brain Software Library.

Results
Post-intervention, there were no significant changes in white matter compared to baseline. Post-intervention, individuals with RRMS performed significantly better on the Symbol Digit Modalities Test (SDMT), reported fewer perceived memory problems, and endorsed less fatigue. Performance was not significantly different on Trails or Digit Span, and there were no significant changes in reports of mood.

Conclusion
Although 12 weeks of speeded walking did not improve white matter integrity, exercise may hold promise for managing some symptoms of RRMS in the context of this study population.