Miracle-dz/UniFAR-FTUs huggingface dataset:
ADAMDEC1 Is a Metzincin Metalloprotease with Dampened Proteolytic Activity

Background: ADAMDEC1 is a putative ADAM-like metalloprotease with a short domain structure and a noncanonical active site. Results: Recombinant ADAMDEC1 cleaves α2-macroglobulin and casein. The activity is significantly enhanced upon reconstituting the consensus zinc-binding site. Conclusion: ADAMDEC1 is secreted as a proteolytic active, glycosylated metalloprotease. Significance: The ADAMDEC1 has adapted a reduced catalytic activity, possibly compensating the loss of auxiliary specificity determining domains. ADAMDEC1 (Decysin-1) is a putative ADAM (a disintegrin and metalloprotease)-like metalloprotease with an unknown physiological role, selectively expressed in mature dendritic cells and macrophages. When compared with other members of the ADAM family, ADAMDEC1 displays some unusual features. It lacks the auxiliary cysteine-rich, EGF, and transmembrane domains, as well as the cytoplasmic tail. The active site of ADAMDEC1 is unique by being the only mammalian ADAM protease with a non-histidine zinc ligand, having an aspartic acid residue instead. Here we demonstrate that ADAMDEC1, despite these unique features, functions as an active metalloprotease. Thus, ADAMDEC1 is secreted as a mature, glycosylated, and proteolytically active metalloprotease, capable of cleaving macromolecular substrates. In the recombinant form, three of the four potential N-linked glycosylation sites are modified by carbohydrate attachment. Substitution of basic residues at the predicted proprotein convertase cleavage site blocks proprotein processing, revealing both specific ADAMDEC1-dependent and specific ADAMDEC1-independent cleavage of the prodomain. The pro-form of ADAMDEC1 does not have proteolytic activity, demonstrating that the prodomain of ADAMDEC1, like in other members of the ADAM family, confers catalytic latency. Interestingly, the proteolytic activity of mature ADAMDEC1 can be significantly enhanced when a canonical ADAM active site with three zinc-coordinating histidine residues is introduced.
Types of parental involvement in CBT with anxious youth: a preliminary meta-analysis.

OBJECTIVE Meta-analytic studies have not confirmed that involving parents in cognitive behavior therapy (CBT) for anxious children is therapeutically beneficial. There is also great heterogeneity in the type of parental involvement included. We investigated parental involvement focused on contingency management (CM) and transfer of control (TC) as a potential outcome moderator using a meta-analysis with individual patient data. METHOD Investigators of randomized controlled trials (RCTs) of CBT for anxious children, identified systematically, were invited to submit their data. Conditions in each RCT were coded based on type of parental involvement in CBT (i.e., low involvement, active involvement without emphasis on CM or TC, active involvement with emphasis on CM or TC). Treatment outcomes were compared using a 1-stage meta-analysis. RESULTS All cases involved in active treatment (894 of 1,618) were included for subgroup analyses. Across all CBT groups, means of clinical severity, anxiety, and internalizing symptoms significantly decreased posttreatment and were comparable across groups. The group without emphasis on CM or TC showed a higher proportion with posttreatment anxiety diagnoses than the low-involvement group. Between posttreatment and 1-year follow-up, the proportion with anxiety diagnoses significantly decreased in CBT with active parental involvement with emphasis on CM or TC, whereas treatment gains were merely maintained in the other 2 groups. CONCLUSIONS CBT for anxious children is an effective treatment with or without active parental involvement. However, CBT with active parental involvement emphasizing CM or TC may support long-term maintenance of treatment gains. RESULTS should be replicated as additional RCTs are published.
Gluten Psychosis: Confirmation of a New Clinical Entity

Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients with symptoms that respond to removal of gluten from the diet, after celiac disease and wheat allergy have been excluded. NCGS has been related to neuro-psychiatric disorders, such as autism, schizophrenia and depression. A singular report of NCGS presenting with hallucinations has been described in an adult patient. We report a pediatric case of a psychotic disorder clearly related to NCGS and investigate the causes by a review of literature. The pathogenesis of neuro-psychiatric manifestations of NCGS is unclear. It has been hypothesized that: (a) a “leaky gut” allows some gluten peptides to cross the intestinal membrane and the blood brain barrier, affecting the endogenous opiate system and neurotransmission; or (b) gluten peptides may set up an innate immune response in the brain similar to that described in the gut mucosa, causing exposure from neuronal cells of a transglutaminase primarily expressed in the brain. The present case-report confirms that psychosis may be a manifestation of NCGS, and may also involve children; the diagnosis is difficult with many cases remaining undiagnosed. Well-designed prospective studies are needed to establish the real role of gluten as a triggering factor in neuro-psychiatric disorders.
Burden of neurodevelopmental disorders in low and middle-income countries: A systematic review and meta-analysis

Background: Childhood mortality from infectious diseases has declined steadily in many low and middle-income (LAMIC) countries, with increased recognition of non-communicable diseases such as neurodevelopmental disorders (NDD). There is lack of data on the burden of NDD in LAMIC. Current global burden of these disorders are largely extrapolated from high-income countries. The main objective of the study was therefore to estimate the burden of NDD in LAMIC using meta-analytic techniques. Methods: We systematically searched online databases including Medline/PubMed, PsychoInfo, and Embase for studies that reported prevalence or incidence of NDD. Pooled prevalence, heterogeneity and risk factors for prevalence were determined using meta-analytic techniques. Results: We identified 4,802 records, but only 51 studies met the eligibility criteria. Most studies were from Asia-Pacific (52.2%) and most were on neurological disorders (63.1%). The median pooled prevalence per 1,000 for any NDD was 7.6 (95%CI 7.5-7.7), being 11.3 (11.7-12.0) for neurological disorders and 3.2 (95%CI 3.1-3.3) for mental conditions such as attention-deficit hyperactivity disorder (ADHD). The type of NDD was significantly associated with the greatest prevalence ratio in the multivariable model (PR=2.6(95%CI 0.6-11.6) (P>0.05). Incidence was only reported for epilepsy (mean of 447.7 (95%CI 415.3-481.9) per 100,000). Perinatal complications were the commonest risk factor for NDD. Conclusion: The burden of NDD in LAMIC is considerable. Epidemiological surveys on NDD should screen all types of NDD to provide reliable estimates.
Annihilation of dislocations during tensile and cyclic deformation and limits of dislocation densities

Abstract It is proposed that, during dislocation glide at low temperatures, both screw and non-screw dislocations annihilate mutually with dislocations of opposite sign approaching on closely neighbouring glide planes. The experimental evidence is summarized and possible mechanisms are discussed. Phenomenological models of dislocation accumulation during deformation, taking into account the annihilation of dislocations, are formulated. The analysis of selected examples of tensile and cyclic deformation of f.c. c. and b.c.c. metal crystals demonstrates that annihilation of edge and/or screw dislocations occurs during strain hardening and can lead to steady state deformation. It follows that the dislocation densities introduced during deformation cannot exceed well-defined upper limits that are distinctly lower than the hypothetical upper limits estimated for the static case. The observations suggest that the critical spacings of dislocation pairs that annihilate are ∼. 50–500 nm for screw and ∼ 1·6 nm for ed.
A hybrid approach to determining cornea mechanical properties using a combination of inverse finite element analysis and experimental techniques

It is of great clinical importance to predict the behaviour of the cornea in various diseases and post-surgical recovery. Therefore, a numerical model that is able to simulate the corneal behaviour, considering corneal material properties obtained from individuals is highly desirable. In this work a combined numerical-experimental technique has been developed that can characterize the mechanical properties of a cornea properties from two aspects: time-dependency and spatial variation. Initially, an analysis of the material properties of porcine corneas was performed to investigate the time-dependent behaviour of the cornea. A simple stress relaxation test was used to determine the viscoelastic properties of a cornea and a rheological model was built based on the Generalized Maxwell (GM) approach. A validation experiment using nano-indentation showed that an isotropic GM model was insufficient for describing the corneal time-dependent behaviour when exposed to a complex stress state. A technique was proposed that takes into account the microstructural composition of the cornea and is based on a combination of nano-indentation experiment, isotropic and transversely isotropic numerical models, and an inverse finite element method. The good agreement using this method suggests that this is a promising technique for measuring the time-dependent properties of the cornea. The spatial variation of the properties was then investigated. This time, the long term structural response of the cornea was targeted. A full field displacement response of a loaded cornea was evaluated from Optical Coherence Tomography (OCT) volume reconstructions of the cornea using Digital Volume Correlation (DVC). The inverse finite element method was employed with two models sequentially; first, a radially partitioned model and then a circumferentially partitioned model, in order to recover the elastic parameters in radial and circumferential directions. The good agreement using this method suggests that this is a promising and reliable technique for identifying the distribution of the corneal properties. In this research, we have shown that it is possible to determine the local time-dependent properties of the cornea and the in-depth (2D) distribution of the properties using the hybrid technique. This technique has the potential to be implemented in vivo. However, further work should focus on the feasibility of this technique in practice.
Distinctiveness Benefits Novelty (and Not Familiarity), but Only Up to a Limit: The Prior Knowledge Perspective

Novelty is a pivotal player in cognition, and its contribution to superior memory performance is a widely accepted convention. On the other hand, mnemonic advantages for familiar information are also well documented. Here, we examine the role of experimental distinctiveness as a potential explanation for these apparently conflicting findings. Across two experiments, we demonstrate that conceptual novelty, an unfamiliar combination of familiar constituents, is sensitive to its experimental proportions: Improved memory for novelty was observed when novel stimuli were relatively rare. Memory levels for familiar items, in contrast, were completely unaffected by experimental proportions, highlighting their insensitivity to list-based distinctiveness. Finally, no mnemonic advantage for conceptual novelty over familiarity was observed even when novel stimuli were extremely rare at study. Together, these results imply that novel and familiar items are processed via partially distinct mechanisms, with (at least some facets of) novelty not providing a mnemonic advantage over familiarity.
Stopping antithrombotic therapy after acute upper gastrointestinal bleeding is associated with reduced survival

Introduction Antithrombotic drugs are often stopped following acute upper gastrointestinal bleeding (AUGIB) and frequently not restarted. The practice of antithrombotic discontinuation on discharge and its impact on outcomes are unclear. Objective To assess whether restarting antithrombotic therapy, prior to hospital discharge for AUGIB, affected clinical outcomes. Design Retrospective cohort study. Setting University hospital between May 2013 and November 2014, with median follow-up of 259 days. Patients Patients who underwent gastroscopy for AUGIB while on antithrombotic therapy. Interventions Continuation or cessation of antithrombotic(s) at discharge. Main outcomes measures Cause-specific mortality, thrombotic events, rebleeding and serious adverse events (any of the above). Results Of 118 patients analysed, antithrombotic treatment was stopped in 58 (49.2%). Older age, aspirin monotherapy and peptic ulcer disease were significant predictors of antithrombotic discontinuation, whereas dual antiplatelet use predicted antithrombotic maintenance. The 1-year postdischarge mortality rate was 11.3%, with deaths mainly due to thrombotic causes. Stopping antithrombotic therapy at the time of discharge was associated with increased mortality (HR 3.32; 95% CI 1.07 to 10.31, P=0.027), thrombotic events (HR 5.77; 95% CI 1.26 to 26.35, P=0.010) and overall adverse events (HR 2.98; 95% CI 1.32 to 6.74, P=0.006), with effects persisting after multivariable adjustment for age and peptic ulcer disease. On subgroup analysis, the thromboprotective benefit remained significant with continuation of non-aspirin regimens (P=0.016). There were no significant differences in postdischarge bleeding rates between groups (HR 3.43, 0.36 to 33.04, P=0.255). Conclusion In this hospital-based study, discontinuation of antithrombotic therapy is associated with increased thrombotic events and reduced survival.
Malignancy characterization of hepatocellular carcinoma using hybrid texture and deep features

Malignancy of hepatocellular carcinoma (HCC) is significant to establish a therapeutic strategy preoperatively for liver cancer and is one of critical issues that influence recurrence and patient survival. Recently, quantitative texture feature of HCC in arterial phase of Contrast-enhanced MR has been shown to be promising for malignancy characterization of HCC. However, such texture feature is low-level, which is usually insufficient to capture the complicated characteristics of HCC. In this work, we propose a systematic method to automatically extract deep feature from the arterial phase of Contrast-enhanced MR using convolution neural network (CNN) in order to characterize malignancy of HCC. Specifically, we resample each 3D tumor in three orthogonal views (Axial, Coronal and Sagittal) independently to increase training sets, and train one CNN for each view to generate its corresponding deep feature. We investigate a multi-kernel feature fusion method that can fuse deep features derived from three views or fuse deep feature and texture feature in a kernel space. Our experimental results demonstrate several interesting conclusions: (1) deep feature significantly outperforms previous texture feature for malignancy characterization of HCC, (2) fusion of deep feature and texture feature yields best results for malignancy characterization of HCC.
Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients.

BACKGROUND AND OBJECTIVES Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. RESULTS Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7-16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8-10.8 cm) were not at higher risk of cardiovascular adverse events. CONCLUSIONS Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk.
Uncertainty analysis for soil‐terrain models

The aim of the study was to examine how robust soil‐terrain models are to uncertainty in the source elevation data. The study site was a 74 ha agricultural field in Australia. A global positioning system was used to measure elevation and the uncertainty of the measurement, therefore allowing maps of elevation and its uncertainty to be created. Monte‐Carlo simulation with a modified version of Latin Hypercube Sampling was used to create 100 realizations of a slope map. Clay content was measured at 111 sites, and kriging with external drift was used to map clay content where each slope realization was used as a secondary information source. Maps of the mean and standard deviation of clay content across all realizations were created. The standard deviations of clay content were generally small (<4 dag kg−1) and in most parts of the field less than the analytical accuracy of the hydrometer method which was used to measure soil‐clay content in the laboratory. The values in the map of elevation uncertainty were multiplied by 5 and the entire error propagation process was repeated to create a second set of 100 realizations of the clay content. The ratio of the uncertainty in the original DEM was 5:1 when compared with that in the perturbed DEM, i.e. it was multiplied by 5. The ratio between the standard deviation in the two clay‐content maps was 3.79:1, which indicates a reduction in uncertainty through the modelling process. The results showed that the soil‐terrain model performs well for the study area, and it is not very sensitive to DEM errors. We conclude that input uncertainty tests as shown in this study should accompany soil mapping studies where secondary information is used in the prediction mdoel.
Generation and functional characterization of MDSC-like cells

ABSTRACT Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14+HLA-DRlowphenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes. Addition of IL-10-APC increased the immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4 on moDC. Moreover, CD14+HLA-DRlow MDSC isolated from healthy donors expressed high levels of osteoactivin, which was even further upregulated by the auxiliary addition of IL-10. Using transcriptome analysis, we identified a set of molecules and pathways mediating these effects. In addition, we found that IL-10-APC as well as human isolated MDSC expressed higher levels of programmed death (PD)-1, PD-ligand-1 (PD-L1), glucocorticoid-induced-tumor-necrosis-factor-receptor-related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4, PD-1 or PD-L1 on MDSC by using blocking antibodies restored the stimulatory capacity of DC in co-incubation experiments. Activation of MDSC with Dectin-1 ligand curdlan reduced the expression of osteoactivin and PD-L1. Our results demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are profoundly involved in the inhibitory effects of MDSC on DC function and might be promising tools for clinical application.
ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment

Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM+ CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER+/HER2− advanced breast cancer receiving everolimus/exemestane. Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM+ CTC fractions: 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment (P = 0.023, Fisher exact test). Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500–10. ©2017 AACR.