Miracle-dz/UniFAR-FTUs huggingface dataset:
MRA versus DSA for the follow-up imaging of intracranial aneurysms treated using endovascular techniques: a meta-analysis

Background Treated aneurysms must be followed over time to ensure durable occlusion, as more than 20% of endovascularly treated aneurysms recur. While digital subtraction angiography (DSA) remains the gold standard, magnetic resonance angiography (MRA) is attractive as a non-invasive follow-up technique. Two different MRA techniques have traditionally been used: time-of-flight (TOF) and contrast-enhanced (CE) MRA. We analysed data from studies comparing MRA techniques with DSA for the follow-up of aneurysms undergoing endovascular treatment. Subgroup analysis of stent-assisted coiling (SAC) and flow diversion (FD) techniques was completed. Methods Comprehensive searches using the Embase, PubMed, and Cochrane databases were performed and updated to November 2018. Pooled sensitivity and specificity were calculated using aneurysm occlusion status as defined by the Raymond–Roy occlusion grading scale. Results The literature search yielded 1579 unique titles. Forty-three studies were included. For TOF-MRA, sensitivity and specificity of all aneurysms undergoing endovascular therapy were 88% and 94%, respectively. For CE-MRA, the sensitivity and specificity were 88% and 96%, respectively. For SAC and FD techniques, sensitivity and specificity of TOF-MRA were 86% and 95%, respectively. CE-MRA had sensitivity and specificity of 90% and 92%. Conclusion MRA is a reliable modality for the follow-up of aneurysms treated using endovascular techniques. While the data are limited, MRA techniques can also be used to reliably follow patients undergoing FD and SAC. However, clinical factors must be used to optimize follow-up regimens for individual patients.
Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up

Abstract Background Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. Patients and methods Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator’s choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR. Results A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy. Conclusions Long-term results (>2 years’ follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC. Trial registration ClinicalTrials.gov: NCT02256436.
Assessing acceptance of electric automated vehicles after exposure in a realistic traffic environment

After years of hypothetical surveys and simulator studies, automated vehicles (AVs) are now being tested in realistic traffic environments adding validity to knowledge about their acceptance. We present data from a pilot test with participants (n = 125) after experiencing a ride in an electric AV on a large clinic area in Berlin, Germany. As a first contribution, we bridge the gap between missing definitions of key constructs, confusion about their operationalisations, and a rigorous test of their statistical properties and data structure by examining scales on acceptance, trust, perceived safety, intention to use, and—for the first time applied to AVs—the emotions amusement, fear, surprise, and boredom. Tests of reliability and normality were satisfying for almost all constructs (Cronbach’s alphas ≥ .69; six of eight scales normally distributed). The vehicles were accepted (M = 1.22; SD = 0.70; range -2 to 2), trusted (M = 3.29; SD = 0.81; range 1 to 5), and perceived as safe (M = 3.29; SD = 1.03; range 1 to 5). However, factor analyses did not reflect the hypothesised data structure, and validity concerns question the suitability of some constructs for attitude assessment of electric AVs. Our open item for comments added valuable insights in qualitative aspects of user attitudes towards electric AVs regarding driving style, technical features, and (unsettling) audio-visual feedback. We thus argue for broader conceptualisations of key constructs based on interdisciplinary exchange and multi-methodical study designs.
AMPA‐preferring glutamate receptors in cochlear physiology of adult guinea‐pig

1 The present study was designed to determine which glutamate (Glu) receptors are involved in excitatory neurotransmission at the first auditory synapse between the inner hair cells and the spiral ganglion neurons. 2 The Glu receptors present at the membrane level were investigated on isolated spiral ganglion neuron somata from guinea‐pigs by whole‐cell voltage‐clamp measurements. Glu and AMPA induced a fast onset inward current that was rapidly desensitized, while kainate induced only a non‐desensitizing, steady‐state current. NMDA induced no detectable current. 3 To further discriminate between the AMPA and kainate receptors present, we used the receptor‐specific desensitization blockers, cyclothiazide and concanavalin A. While no effect was observed with concanavalin A, cyclothiazide greatly enhanced the Glu‐, AMPA‐ and kainate‐induced steady‐state currents and potentiated Glu‐induced membrane depolarization. 4 To extrapolate the results obtained from the somata to the events occurring in situ at the dendrites, the effects of these drugs were evaluated in vivo. Cyclothiazide reversibly increased spontaneous activity of single auditory nerve fibres, while concanavalin A had no effect, suggesting that the functional Glu receptors on the somata may be the same as those at the dendrites. 5 The combination of a moderate‐level sound together with cyclothiazide increased and subsequently abolished the spontaneous and the sound‐evoked activity of the auditory nerve fibres. Histological examination revealed destruction of the dendrites, suggesting that cyclothiazide potentiates sound‐induced Glu excitotoxicity via AMPA receptors. 6 Our results reveal that fast synaptic transmission in the cochlea is mainly mediated by desensitizing AMPA receptors.
The coagulant response in sepsis and inflammation

Summary Critically ill patients often have systemic activation of both inflammation and coagulation. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may have major consequences for the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Activation of the coagulation system and ensuing thrombin generation is dependent on an inter-leukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by tissue factor pathway inhibitor. Simultaneously, endothelial-bound anticoagulant mechanisms, in particular the protein C system and the antithrombin system, are shut-off by pro-inflammatory cytokines. Modulation of inflammatory activity by activation of coagulation also occurs by various mechanisms. Activated coagulation proteases, such as the tissue factor-factor VIIa complex, factor Xa and thrombin can bind to protease-activated receptors on various cells and the ensuing intracellular signaling leads to increased production of pro-inflammatory cytokines and chemo kines. Physiological anticoagulants can modulate inflammatory activity as well. Increasing knowledge on the various mechanisms underlying activation of inflammation and coagulation may lead to better (adjunctive) management strategies in critically ill patients.
Circulating osteocalcin as a bone-derived hormone is inversely correlated with body fat in patients with type 1 diabetes

The objective of the present study was to investigate the correlations between serum undercarboxylated osteocalcin (ucOC) or osteocalcin (OC) concentrations and %body fat, serum adiponectin and free-testosterone concentration, muscle strength and dose of exogenous insulin in patients with type 1 diabetes. We recruited 73 Japanese young adult patients with childhood-onset type 1 diabetes. All participants were receiving insulin replacement therapy. The correlations between logarithmic serum ucOC or OC concentrations and each parameter were examined. Serum ucOC and OC concentrations were inversely correlated with %body fat (r = -0.319, P = 0.007; r = -0.321, P = 0.006, respectively). Furthermore, multiple linear regression analyses were performed to determine whether or not serum ucOC or OC concentrations were factors associated with %body fat. Serum ucOC and OC concentrations remained significant factors even after adjusting for gender, HbA1c, body weight-adjusted total daily dose of insulin and duration of diabetes (β = -0.260, P = 0.027; β = -0.254, P = 0.031, respectively). However, serum ucOC and OC concentrations were not correlated with serum adiponectin or free-testosterone concentrations, muscle strength or dose of exogenous insulin. In conclusion, our study demonstrates the inverse correlation between serum ucOC or OC concentrations and body fat in patients with type 1 diabetes.
An Exploration of Real-World Analogical Problem Solving in Novices

Despite the postulated importance of analogising to human cognition, the study of analogical problem solving in the laboratory has found disappointing results. Providing an analogue to a participant prior to asking them to solve a problem gives only a small benefit at best. Recently, studies outside the laboratory have suggested that experts frequently use analogies in realworld situations. It is less clear whether novices can also spontaneously invoke and use analogies to solve realistic problems. In the current investigation, undergraduates were observed solving a large-scale management problem over two weeks. It was found that many analogies were produced (on average 4.6 per one-hour session), and that 77% of these analogies reflected a structural rather than a superficial mapping between a base and a target. It was also determined that 56% of these structural analogies involved non-trivial mappings of higher-order relations. Further, it was found that analogies were drawn to serve two different purposes: problem solving and illustration. In generating illustrative analogies, participants frequently made superficial mappings, but when generating analogies to solve problems, they never made purely superficial mappings.
Long-term every-other-day administration of DMAMCL has little effect on aging and age-associated physiological decline in mice

The activation of transcription factor NF-κB is currently identified as one of the driving forces to the aging process. Genetic impairment of NF-κB signaling pathway or pharmacological inhibition of NF-κB activity has been shown to extend healthspan and lifespan in animal models, and delay or reduce many age-related symptoms. However, the aging intervention strategies based on NF-κB inhibition by the suitable small molecular compound is currently still lacking. The water-soluble dimethylaminomicheliolide (DMAMCL), can inhibit NF-κB activity and is currently undergoing clinical trials. In this study, we showed that 15 months of DMAMCL administration started in 1-year old male mice was well-tolerated and safe, and improved or had little effect on some age-associated symptoms, such as neurobehavioral phenotypes, physical performance, cardiac function, hematological parameters, immune aging phenotypes, clinical chemistry parameters, and glucose homeostasis. At the molecular level, DMAMCL administration mitigated serum levels of several age-associated inflammatory cytokines, including IL-6, IL-1α, IL-1β, TNF-α, IFN-γ, and CXCL2, and inhibited NF-κB activity in several aged tissues. Collectively, our results indicate that current strategy of DMAMCL administration may has little effect on aging process in mice, and provide basic clues to further exploit the possibility of DMAMCL-based aging intervention to promote healthy aging.
Categorization of species as native or nonnative using DNA sequence signatures without a complete reference library

Abstract New genetic diagnostic approaches have greatly aided efforts to document global biodiversity and improve biosecurity. This is especially true for organismal groups in which species diversity has been underestimated historically due to difficulties associated with sampling, the lack of clear morphological characteristics, and/or limited availability of taxonomic expertise. Among these methods, DNA sequence barcoding (also known as “DNA barcoding”) and by extension, meta‐barcoding for biological communities, has emerged as one of the most frequently utilized methods for DNA‐based species identifications. Unfortunately, the use of DNA barcoding is limited by the availability of complete reference libraries (i.e., a collection of DNA sequences from morphologically identified species), and by the fact that the vast majority of species do not have sequences present in reference databases. Such conditions are critical especially in tropical locations that are simultaneously biodiversity rich and suffer from a lack of exploration and DNA characterization by trained taxonomic specialists. To facilitate efforts to document biodiversity in regions lacking complete reference libraries, we developed a novel statistical approach that categorizes unidentified species as being either likely native or likely nonnative based solely on measures of nucleotide diversity. We demonstrate the utility of this approach by categorizing a large sample of specimens of terrestrial insects and spiders (collected as part of the Moorea BioCode project) using a generalized linear mixed model (GLMM). Using a training data set of known endemic (n = 45) and known introduced species (n = 102), we then estimated the likely native/nonnative status for 4,663 specimens representing an estimated 1,288 species (412 identified species), including both those specimens that were either unidentified or whose endemic/introduced status was uncertain. Using this approach, we were able to increase the number of categorized specimens by a factor of 4.4 (from 794 to 3,497), and the number of categorized species by a factor of 4.8 from (147 to 707) at a rate much greater than chance (77.6% accuracy). The study identifies phylogenetic signatures of both native and nonnative species and suggests several practical applications for this approach including monitoring biodiversity and facilitating biosecurity.
Ameliorative effects of Annona muricata Linn. (Annonaceae) against potassium dichromate-induced hypertension in vivo: involvement of Kim-1/p38 MAPK/Nrf2 signaling

Abstract Background Recently, the incidences of hypertension and environmental pollution have increased significantly. This study investigates the antihypertensive effect of Annona muricata extract against K2Cr2O7-induced hypertension. Methods Fifty rats were used for this study, which were divided into five groups of 10 rats each. Rats in Group A received normal saline, and those in Groups B, C, D, and E were treated with A. muricata extract alone at 250 mg/kg, K2Cr2O7 at 30 mg/kg, pretreated with the extract at 250 mg/kg, and pretreated with gallic acid at 60 mg/kg for 14 days, respectively, and thereafter administered with a single intraperitoneal injection of K2Cr2O7 at 30 mg/kg. Results Administration of K2Cr2O7 significantly increased systolic, diastolic, and mean arterial pressure and caused prolonged QT and QTc intervals. Further, pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg significantly reduced high blood pressure to near-normal values. K2Cr2O7 intoxication led to significant increases in serum advanced oxidative protein products, myeloperoxidase, and xanthine oxidase, while serum nitric oxide (NO) also reduced significantly. Immunohistochemistry of the renal kidney injury molecule (Kim-1) and p38 MAPK showed increased expressions following the administration of K2Cr2O7 together with the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg also increased the expressions of Nrf2 and downregulated Kim-1 and p38. Conclusion Together, we found that pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg normalized the blood pressure, reduced the markers of oxidative stress, and improved the antioxidant defense system and serum NO bioavailability.
Dynamic Contrast-Enhanced MRI to Differentiate Parotid Neoplasms Using Golden-Angle Radial Sparse Parallel Imaging

BACKGROUND AND PURPOSE: Conventional imaging frequently shows overlapping features between benign and malignant parotid neoplasms. We investigated dynamic contrast-enhanced MR imaging using golden-angle radial sparse parallel imaging in differentiating parotid neoplasms. MATERIALS AND METHODS: For this retrospective study, 41 consecutive parotid neoplasms were imaged with dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel imaging using 1-mm in-plane resolution. The temporal resolution was 3.4 seconds for 78.2 seconds and 8.8 seconds for the remaining acquisition. Three readers retrospectively and independently created and classified time-intensity curves as follows: 1) continuous wash-in; 2) rapid wash-in, subsequent plateau; and 3) rapid wash-in with washout. Additionally, time-intensity curve–derived semiquantitative metrics normalized to the ipsilateral common carotid artery were recorded. Diagnostic performance for the prediction of neoplasm type and malignancy was assessed. Subset multivariate analysis (n = 32) combined semiquantitative time-intensity curve metrics with ADC values. RESULTS: Independent time-intensity curve classification of the 41 neoplasms produced moderate-to-substantial interreader agreement (κ = 0.50–0.79). The time-intensity curve classification threshold of ≥2 predicted malignancy with a positive predictive value of 56.0%–66.7%, and a negative predictive value of 92.0%–100%. The time-intensity curve classification threshold of <2 predicted pleomorphic adenoma with a positive predictive value of 87.0%–95.0% and a negative predictive value of 76.0%–95.0%. For all readers, type 2 and 3 curves were associated with malignant neoplasms (P < .001), and type 1 curves, with pleomorphic adenomas (P < .001). Semiquantitative analysis for malignancy prediction yielded an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.73–0.99). Combining time-to-maximum and ADC predicts pleomorphic adenoma better than either metric alone (P < .001). CONCLUSIONS: Golden-angle radial sparse parallel MR imaging allows high spatial and temporal resolution permeability characterization of parotid neoplasms, with a high negative predictive value for malignancy prediction. Combining time-to-maximum and ADC improves pleomorphic adenoma prediction compared with either metric alone.
Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies.

BACKGROUND Prosthetic joint infections (PJIs) often require long-course antibiotic therapy. However, recent studies argue against the current practice and raise concerns such as the development of antibiotic resistance, side effects of medications and medical costs. OBJECTIVES To review and compare the outcomes of short-course and long-course antibiotics in PJIs. METHODS We conducted a systemic review and meta-analysis using a predefined search term in PubMed and EMBASE databases. Studies that met the inclusion criteria from inception to June 2018 were included. The quality of the included studies was assessed. RESULTS A total of 10 articles and 856 patients were analysed, comprising 9 observational studies and 1 randomized controlled trial. Our meta-analysis showed no significant difference between short-course and long-course antibiotics (relative risk = 0.87, 95% CI = 0.62-1.22). Additionally, the older the studied group was, the more short-course antibiotics were favoured. CONCLUSIONS When treating PJI patients following debridement, antibiotics and implant retention, an 8 week course of antibiotic therapy for total hip arthroplasty and a 75 day course for total knee arthroplasty may be a safe approach. For two-stage exchange, a shorter duration of antibiotic treatment during implant-free periods is also generally safe with the usage of antibiotic-loaded cement spacers.
Automatic Image Quality Assessment with Application in Biometrics

A method using local features to assess the quality of an image, with demonstration in biometrics, is proposed. Recently, image quality awareness has been found to increase recognition rates and to support decisions in multimodal authentication systems significantly. Nevertheless, automatic quality assessment is still an open issue, especially with regard to general tasks. Indicators of perceptual quality like noise, lack of structure, blur, etc. can be retrieved from the orientation tensor of an image, but there are few studies reporting on this. Here we study the orientation tensor with a set of symmetry descriptors, which can be varied according to the application. Allowed classes of local shapes are generically provided by the user but no training or explicit reference information is required. Experimental results are given for fingerprint. Furthermore, we indicate the applicability of the proposed method to face images.