Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteological Re‐Assessment and Taxonomic Revision of “Tanius laiyangensis” (Ornithischia: Hadrosauroidea) from the Upper Cretaceous of Shandong, China

Tanius is the earliest named ornithischian genus from China. Since 1929, three species of this genus, namely T. sinensis (the type species), “T. chingkankouensis” and “T. laiyangensis”, have been reported based on remains from the Wangshi Group of Shandong, China, and were previously recognized as hadrosaurines. Following the recent achievement of consensus on the phylogenetic placement of T. sinensis outside Hadrosauridae, the assignments of the “T. chingkankouensis” and “T. laiyangensis” material of hadrosaurid origin to the genus Tanius become problematic. Related taxonomic issues of “T. laiyangensis” therefore need re‐appraisals. Here, we provide an overall taxonomic revision of “T. laiyangensis” from the Jingangkou Formation of northeast Shandong, by means of approaches of comparative anatomy, phylogeny and geometric morphometrics. Our osteological comparisons confirm the hadrosaurine affinity of “T. laiyangensis”, given the presence of a suite of characters largely typical of Hadrosaurinae in the single specimen (i.e., a nearly complete sacrum and a partial right ilium), including a dorsoventrally narrow central plate of the ilium with the depth/length ratio <0.80. In the proposed phylogenetic framework, “T. laiyangensis” is inferred to be a member of Kritosaurini within Hadrosaurinae, as the sister taxon to Secernosaurus koerneri. The relative warp analysis on the lateral outline of the supraacetabular process also reveals a close resemblance of shape between the two species. Based on these different lines of evidence and considering no identification of any diagnostic characters from the specimen, we argue that the “T. laiyangensis” material comes from an indeterminate kritosaurin hadrosaurine in Asia. Anat Rec, 303:790–800, 2020. © 2019 Wiley Periodicals, Inc.
Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism

Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Parkinson's disease is a movement disorder with characteristic motor features that arise due to the loss of dopaminergic neurons from the substantia nigra. Although symptomatic treatment by the dopamine precursor levodopa and dopamine agonists can improve motor symptoms, no disease-modifying therapy exists yet. Here, we show that Emapunil (AC-5216, XBD-173), a synthetic ligand of the translocator protein 18, ameliorates degeneration of dopaminergic neurons, preserves striatal dopamine metabolism, and prevents motor dysfunction in female mice treated with the MPTP, as a model of parkinsonism. We found that Emapunil modulates the inositol requiring kinase 1α (IRE α)/X-box binding protein 1 (XBP1) unfolded protein response pathway and induces a shift from pro-inflammatory toward anti-inflammatory microglia activation. Previously, Emapunil was shown to cross the blood–brain barrier and to be safe and well tolerated in a Phase II clinical trial. Therefore, our data suggest that Emapunil may be a promising approach in the treatment of Parkinson's disease. SIGNIFICANCE STATEMENT Our study reveals a beneficial effect of Emapunil on dopaminergic neuron survival, dopamine metabolism, and motor phenotype in the MPTP mouse model of parkinsonism. In addition, our work uncovers molecular networks which mediate neuroprotective effects of Emapunil, including microglial activation state and unfolded protein response pathways. These findings not only contribute to our understanding of biological mechanisms of translocator protein 18 (TSPO) function but also indicate that translocator protein 18 may be a promising therapeutic target. We thus propose to further validate Emapunil in other Parkinson's disease mouse models and subsequently in clinical trials to treat Parkinson's disease.
Appropriateness of deep vein thrombosis (DVT) prophylaxis use among medical inpatients: a DVT risk alert tool (DRAT) study.

INTRODUCTION Increasing incidence of Venous Thromboembolism (VTE) has complicated treatment courses for hospitalised patients. Despite recommendation to support deep vein thrombosis (DVT) risk assessment and appropriate use of prophylaxis in medical inpatients, it is either neglected or prescribed unnecessarily by the clinicians. This study aimed to assess and compare the appropriateness of DVT prophylaxis prescribing between usual care versus a pharmacist-driven DVT Risk Alert Tool (DRAT) intervention among hospitalised medical patients. METHODS A prospective pre- and post-intervention study was conducted among medical inpatients in a Malaysian secondary care hospital. DVT and bleeding risks were stratified using validated Padua Risk Assessment Model (RAM) and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Risk Assessment Model. Pharmacist-driven DRAT was developed and implemented post-interventional phase. DVT prophylaxis use was determined and its appropriateness was compared between pre and post study using multivariate logistic regression with IBM SPSS software version 21.0. RESULTS Overall, 286 patients (n=142 pre-intervention versus n=144 post-intervention) were conveniently recruited. The prevalence of DVT prophylaxis use was 10.8%. Appropriate thromboprophylaxis prescribing increased from 64.8% to 68.1% post-DRAT implementation. Of note, among high DVT risk patients, DRAT intervention was observed to be a significant predictor of appropriate thromboprophylaxis use (14.3% versus 31.3%; adjusted odds ratio=2.80; 95% CI 1.01 to 7.80; p<0.05). CONCLUSION The appropriateness of DVT prophylaxis use was suboptimal but doubled after implementation of DRAT intervention. Thus, an integrated risk stratification checklist is an effective approach for the improvement of rational DVT prophylaxis use.
Unity in diversity: mapping healthcare interpreting studies (2007-2017)

ABSTRACT This paper intends to examine the evolution of healthcare interpreting studies published in SSCI and A&HCI journals between 2007 and 2017. A total of 40 journal articles have been selected from 23 SSCI or A&HCI journals, covering journals on translation and interpreting, linguistics and communication as well as healthcare studies. Thematically, articles selected fall in such four major types as socio-political background, healthcare interpreting practice, and education and training. Methodologically, based on an existing framework of classification, articles selected are grouped into four categories, namely, pure empirical research, pro-empirical research, pro-non-empirical research, and pure non-empirical research. Built on such a characterization of past studies on healthcare interpreting, this paper serves as a general map of relevant studies of this sub-field in the past decade and attempts to provide recommendations on research directions in the future. Such directions include the integration and alignment between the T & I community and the healthcare research community in the study of healthcare interpreting, the development of inter-disciplinary perspectives on the socio-political background of healthcare interpreting, and the expansion of research that is specialty-based, informed and driven.
Association of Myocardial Deformation With Outcome in Asymptomatic Aortic Stenosis With Normal Ejection Fraction

Background—Current guidelines recommend intervention for symptomatic aortic stenosis, but the management of asymptomatic aortic stenosis remains controversial. As left ventricular global longitudinal strain (GLS) has been shown to predict cardiovascular outcome, we sought to find whether its use could guide the assessment of risk in these patients. Methods and Results—We prospectively followed 79 patients with severe asymptomatic aortic stenosis (39 men; mean age, 77 ± 12 years; aortic valve [AV] area index, 0.36 cm2/m2). In addition to standard echocardiography, speckle strain was measured to assess GLS. Patients were followed for cardiac death and AV replacement driven by symptom development. A multivariable Cox regression was performed to identify associations with events. During 23 ± 20 months, 3 patients had cardiac death and 49 underwent AV replacement. Event-free survival was 72 ± 5% at 1 year, 50 ± 5% at 2 years, and 24 ± 5% at 4 years. Death and AV replacement were predicted by GLS (hazard ratio [HR], 1.14 [95% CI, 1.01–1.28]; P=0.037), as well as extent of AV calcification (HR, 2.44 [95% CI, 1.17–5.12]; P=0.018), peak transaortic pressure gradient (HR, 1.03 [95% CI, 1.01–1.04]; P<0.001), valvulo-arterial impedance (HR, 1.32 [95% CI, 1.04–1.67]; P=0.045), and Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality (HR, 0.95 [95% CI, 0.90–1.00]; P=0.052). A mean absolute GLS <15% was associated with a significant excess mortality, and this measurement added incremental prognostic value to the Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality, transaortic peak pressure gradient, AV calcification, and valvulo-arterial impedance. Conclusions—GLS is associated with outcomes in patients with severe asymptomatic aortic stenosis, incremental to other clinical and echocardiographic variables.
Antimalarial drugs and their metabolites are potent Zika virus inhibitors

Studies aimed at repurposing existing drugs revealed that some antimalarial compounds possess anti‐Zika virus (anti‐ZIKV) activity. Here, we further tested 14 additional antimalarial drugs and their metabolites or analogs for anti‐ZIKV activity using a phenotypic screening approach. We identified four compounds with varying anti‐ZIKV activity, including a metabolite of amodiaquine termed desethylamodiaquine (DAQ) and N‐desethylchloroquine (DECQ), a metabolite of chloroquine, which both exhibited low micromolar effective concentrations against three different ZIKV strains. Two other compounds termed dihydroartemisinin (DHA) and quinidine (QD) exhibited only partial inhibition of ZIKV replication. Characterization of the inhibitory mechanisms of DAQ and DECQ showed that both drugs target the entry step as well as postentry events of the viral replication cycle. These hits represent attractive starting points for future optimization of new anti‐ZIKV drug candidates derived from antimalarial drugs and their analogs.
Assessment of the Generalizability of an eConsult Service through Implementation in a New Health Region

Introduction: Excessive wait times for specialist care are a significant issue in many countries. Electronic consultation (eConsult) services have demonstrated the ability to improve access to specialist care. In this article, we evaluated the implementation of a successful eConsult service in a new jurisdiction to test its generalizability. Methods: We used a multimethod approach to evaluate the Champlain Building Access to Specialists through eConsultation eConsult service's implementation in the South East Local Health Integration Network of Ontario, Canada. Our quantitative analysis drew on use data collected automatically by the service and survey responses completed between February 1, and June 15, 2017. For our qualitative analysis, we conducted a thematic analysis of 3 focus groups with primary care providers and specialists participating in the pilot study. Results: Forty-nine out of the potential 219 primary care providers in Kingston submitted 301 cases to 24 specialty groups during the study period. Monthly case volume grew from 15 in February to 90 in May. The most frequently requested specialties included dermatology (n = 59), cardiology (n = 27), and gastroenterology (n = 26). Specialists responded in a median of 2 days, and a referral was originally contemplated but ultimately avoided in 40% of cases. Providers spoke positively of the service, citing high levels of satisfaction, enhanced collegiality, increased trust, and improved patient flow. Conclusions: Adoption of the eConsult service in the South East Local Health Integration Network was successful. The service exceeded all adoption targets, and the number of completed cases demonstrated a consistently upward trend, suggesting continued growth beyond the study's duration. The service's rate of adoption, high levels of satisfaction, and use data similar to other regions all demonstrate eConsult's generalizability.
Emodin protects H9c2 cells from hypoxia-induced injury by up-regulating miR-138 expression

Myocardial infarction (MI) is a common presentation for ischemic heart disease, which is a leading cause of death. Emodin is a Chinese herbal anthraquinone used in several diseases. However, the effect of emodin in hypoxia-induced injury in cardiomyocytes has not been clearly elucidated. Our study aimed to clarify the functions of emodin in hypoxia-induced injury in rat cardiomyocytes H9c2 and explore the underlying mechanism. The effects of emodin on cell viability and apoptosis were analyzed by the Cell counting kit-8 assay and flow cytometry assay, respectively. The cell proliferation- and cell apoptosis-related proteins were detected by western blot. qRT-PCR was used to determine the relative expression of miR-138. Cell transfection was performed to alter miR-138 and MLK3 expression. miR-138 target was performed by dual luciferase activity assay. Sirt1/AKT and Wnt/β-catenin pathways-related factors phosphorylation were analyzed by western blot. Emodin inhibited hypoxia-induced injury in H9c2 cells by promoting cell viability and reducing cell apoptosis. miR-138 was down-regulated by hypoxia treatment but up-regulated by emodin. Up-regulation of miR-138 alleviated hypoxia-induced cell injury. Down-regulation of miR-138 attenuated the growth-promoting effect of emodin on hypoxia-induced injury, whereas up-regulation of miR-138 enhanced the growth-promoting effects of emodin. The underlying mechanism might be by inactivating Sirt1/AKT and Wnt/β-catenin pathways. MLK3 was negatively regulated by miR-138 expression and inactivated Sirt1/AKT and Wnt/β-catenin pathways. Emodin alleviated hypoxia-induced injury in H9c2 cells via up-regulation of miR-138 modulated by MLK3, as well as by activating Sirt1/AKT and Wnt/β-catenin pathways.
Comparison of Colposcopic Biopsy Results of Patients Who have Cytomorphological Normal but HPV 16-18 or Other High-Risk HPV Subtypes Positive

Objective: Current guidelines suggest annual co-test follow-up in non-16/18 high-risk HPV positive patients without abnormal cytologic findings. Considering the relatively high false-negative rates of cervical cytology, a follow-up period of one year might constitute an additional risk for development of cervical malignancies in these patients. The current study aims to evaluate colposcopic biopsy results of cytologically normal patients detected to carry high risk HPV by screening tests. Materials and Methods: A total of 160 patients with normal cervical cytology and high-risk HPV subtypes who underwent colposcopic examination were included in the study. Patients were divided into two groups according to their HPV results: HPV 16-18 and other types (non-16/18 high-risk subtypes). ECC, cervical biopsy, LEEP/conization results were analyzed for both groups. Histopathological results of the groups were compared in terms of ≤LSIL, HSIL and cervical cancer rates. Results: Cervical biopsy results in the “16-18” group were assessed as HSIL in 40 (48.2%) patients, LSIL in 6 patients (7.2%) and normal in 37 (44.6%) patients. ECC results revealed HSIL in 9 (10.8%) patients and LSIL in 1 (1.2%) patient. Nineteen out of 42 patients who underwent LEEP/conization had HSIL (surgical margin positivity was reported in 4 cases), while 3 patients had LSIL. None of the cases had cervical carcinoma. Conclusion: The present study detected that 15.6% of women infected with non-16/18 high-risk HPV subgroups developed ≥HSIL lesions. Although this rate seems lower than HPV 16-18 group, it is still too high to be overlooked. In conclusion, we suggest further clinical trials with larger number of patients to be conducted on this topic.
Effect of alteplase on platelet function and receptor expression

Objective To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function. Methods Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined. Results This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction. Conclusions Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.
Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?

Abstract Background Internal quality control (QC) rules for laboratory tests can be derived from analytical performance specifications (APS) using the six-sigma method. We tested the applicability of this paradigm to routine haemostasis measurements. Methods Three laboratories using different instruments and reagents calculated sigma scores for their prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and antithrombin (AT) measurements. Sigma scores were calculated using biological variation (BV) data from the literature in combination with internal and external QC data. Results Wide ranges in sigma scores for the PT (0.1–6.8), APTT (0.0–4.3), fibrinogen (1.5–8.3) and AT (0.1–2.4) were observed when QC data was combined with the minimum, median and maximum value of BV data, due in particular to a large variation in within-subject and between-subjects coefficients of variation. When the median BV values were applied, most sigma scores were below 3.0, for internal QC data; 75% and for external QC data; 92%. Conclusions Our findings demonstrate that: (1) The sigma scores for common haemostasis parameters are relatively low, and (2) The application of the six-sigma method to BV-derived APS is hampered by the large variation in published BV data. As the six-sigma concept is based on requirements for monitoring, and many haemostasis tests are only designed for diagnostic purposes, a fit-for-purpose APS is needed to achieve clinically relevant quality goals.
Efficacy and reliability of active robotic-assisted total knee arthroplasty compared with conventional total knee arthroplasty: a systematic review and meta-analysis

Background In the field of prosthetics, the ultimate goal is to improve the clinical outcome by using a technique that prolongs the longevity of prosthesis. Active robotic-assisted total knee arthroplasty (TKA) is one such technique that is capable of providing accurate implant position and restoring mechanical alignment. Although relevant studies have been carried out, the differences in the efficacy and reliability between active robotic-assisted TKA and conventional arthroplasty have not yet been adequately discussed. Methods We referenced articles, including randomised controlled trials and comparative retrospective research, from PubMed, Embase, Cochrane Library and Web of Science, in order to compare active robotic-assisted TKA with the conventional technique. Data extraction and quality assessment were conducted for each study. Statistical analysis was performed using Revman V. 5.3. Results Seven studies with a total of 517 knees undergoing TKA were included. Compared with conventional surgery, active robotic TKA showed better outcomes in precise mechanical alignment (mean difference, MD: − 0.82, 95% CI: −1.15 to − 0.49, p < 0.05) and implant position, with lower outliers (p < 0.05), better functional score (Western Ontario and McMaster University, Knee Society Score functional score) and less drainage (MD: − 293.28, 95% CI: − 417.77 to − 168.79, p < 0.05). No significant differences were observed when comparing the operation time, range of motion and complication rates. Conclusion The current research demonstrates that active robotic-assisted TKA surgeries are more capable of improving mechanical alignment and prosthesis implantation when compared with conventional surgery. Further studies are required to investigate the potential benefits and long-term clinical outcomes of active robotic-assisted TKA.
Tuft dendrites of pyramidal neurons operate as feedback-modulated functional subunits

Dendrites of pyramidal cells exhibit complex morphologies and contain a variety of ionic conductances, which generate non-trivial integrative properties. Basal and proximal apical dendrites have been shown to function as independent computational subunits within a two-layer feedforward processing scheme. The outputs of the subunits are linearly summed and passed through a final non-linearity. It is an open question whether this mathematical abstraction can be applied to apical tuft dendrites as well. Using a detailed compartmental model of CA1 pyramidal neurons and a novel theoretical framework based on iso-response methods, we first show that somatic sub-threshold responses to brief synaptic inputs cannot be described by a two-layer feedforward model. Then, we relax the core assumption of subunit independence and introduce non-linear feedback from the output layer to the subunit inputs. We find that additive feedback alone explains the somatic responses to synaptic inputs to most of the branches in the apical tuft. Individual dendritic branches bidirectionally modulate the thresholds of their input-output curves without significantly changing the gains. In contrast to these findings for precisely timed inputs, we show that neuronal computations based on firing rates can be accurately described by purely feedforward two-layer models. Our findings support the view that dendrites of pyramidal neurons possess non-linear analog processing capabilities that critically depend on the location of synaptic inputs. The iso-response framework proposed in this computational study is highly efficient and could be directly applied to biological neurons.
ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials

ABSTRACT Introduction: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e. ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity. Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.