Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Endomyocardial Biopsy in ARVC: Looking Beyond Histology in Search of New Diagnostic Markers

The Role of Endomyocardial Biopsy in ARVC. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by a high incidence of ventricular tachyarrhythmias and sudden cardiac death that appear early in the natural history of the disease and may precede significant ventricular remodeling. The classical pathology of ARVC is degeneration of right ventricular free wall myocardium and its replacement by fat and fibrous tissue. The clinical presentation may be highly variable, however, and genetic penetrance is typically low which makes definitive diagnosis difficult, especially in early stages of the disease. Endomyocardial biopsy (EMB) has not been used widely in the diagnosis of ARVC, in part because pathological changes are usually most conspicuous in the epicardium of the right ventricular free wall and tend to spare the endocardium and interventricular septum. Thus, diagnostic pathological features of ARVC are often not seen in conventional septal biopsies. Diagnostic yield may be increased by sampling the RV free wall or by using 3‐dimensional electroanatomic voltage mapping to identify affected areas, but these approaches can carry increased risk and require specialized equipment and experience. Moreover, diagnostic pathological changes may not be apparent in early disease despite an increased risk of arrhythmias and sudden death. This review considers the role of EMB in the diagnosis of ARVC and highlights recent advances in identifying potential tissue biomarkers that arise early in the disease process and occur diffusely throughout the myocardium. Analysis of conventional EMB using such biomarkers could improve diagnostic sensitivity and accuracy but widespread clinical application of this approach requires further validation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 111‐117, January 2011)
Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR.

BACKGROUND Prenatal diagnosis in pregnancies at risk of single-gene disorders is currently performed using invasive methods such as chorionic villus sampling and amniocentesis. This is in contrast with screening for common aneuploidies, for which noninvasive methods with a single maternal blood sample have become standard clinical practice. METHODS We developed a protocol for noninvasive prenatal diagnosis of inherited single-gene disorders using droplet digital PCR from circulating cell-free DNA (cfDNA) in maternal plasma. First, the amount of cfDNA and fetal fraction is determined using a panel of TaqMan assays targeting high-variability single-nucleotide polymorphisms. Second, the ratio of healthy and diseased alleles in maternal plasma is quantified using TaqMan assays targeting the mutations carried by the parents. Two validation approaches of the mutation assay are presented. RESULTS We collected blood samples from 9 pregnancies at risk for different single-gene disorders, including common conditions and rare metabolic disorders. We measured cases at risk of hemophilia, ornithine transcarbamylase deficiency, cystic fibrosis, β-thalassemia, mevalonate kinase deficiency, acetylcholine receptor deficiency, and DFNB1 nonsyndromic hearing loss. We correctly differentiated affected and unaffected pregnancies (2 affected, 7 unaffected), confirmed by neonatal testing. We successfully measured an affected pregnancy as early as week 11 and with a fetal fraction as low as 3.7% (0.3). CONCLUSIONS Our method detects single-nucleotide mutations of autosomal recessive diseases as early as the first trimester of pregnancy. This is of importance for metabolic disorders in which early diagnosis can affect management of the disease and reduce complications and anxiety related to invasive testing.
Former smoking and early and long‐term graft outcome in renal transplant recipients: a retrospective cohort study

Smoking is associated with unfavourable outcome in solid‐organ transplant recipients. Nicotine may predispose to kidney injury by increasing oxidative stress. We hypothesized that former smoking negatively affects graft outcome in kidney transplant recipients and especially those with delayed graft function (DGF). We included adult recipients of a kidney transplant between 1 January 2003 and 1 October 2015 at Ghent University Hospital and recorded outcomes until 31 October 2015. We used Kaplan–Meier and multivariable Cox proportional hazard analysis to examine the relationship between former smoking at the time of transplantation and the incidence of 10‐year graft loss with and without censoring for death in 1013 participants. We evaluated mean differences in eGFR over time by a random intercept and slope model, considering a linear time effect. After adjusting for potential confounders, a history of smoking was associated with an increased hazard of graft loss (adjusted hazard ratio (aHR) 1.60; 95% CI: 1.17–2.17; P = 0.003) and death‐censored graft loss (aHR 2.29; 95% CI: 1.41–3.72; P = 0.001). The linear time trend of eGFR was different between former and never smokers (P = 0.001). To conclude, former smoking exerts long‐lasting negative effects on graft outcome and this independent of DGF.
Levetiracetam in patients with central neuropathic post‐stroke pain – a randomized, double‐blind, placebo‐controlled trial

Central post‐stroke pain (CPSP) is a severe chronic neuropathic pain condition defined as a spontaneous pain or allodynia corresponding to a vascular lesion. It usually evolves weeks after stroke, and can distinctively impair the quality of life. Treatment is complex and mostly unsatisfactory. We hypothesized that the anti‐epileptic drug levetiracetam (LEV) improves CPSP compared with placebo. The purpose of this study was to examine the efficacy and tolerability of LEV in patients with CPSP.
Coaggregation by the Freshwater Bacterium Sphingomonas natatoria Alters Dual-Species Biofilm Formation

ABSTRACT Coaggregation is hypothesized to enhance freshwater biofilm development. To investigate this hypothesis, the ability of the coaggregating bacterium Sphingomonas natatoria to form single- and dual-species biofilms was studied and compared to that of a naturally occurring spontaneous coaggregation-deficient variant. Attachment assays using metabolically inactive cells were performed using epifluorescence and confocal laser scanning microscopy. Under static and flowing conditions, coaggregating S. natatoria 2.1gfp cells adhered to glass surfaces to form diaphanous single-species biofilms. When glass surfaces were precoated with coaggregation partner Micrococcus luteus 2.13 cells, S. natatoria 2.1gfp cells formed densely packed dual-species biofilms. The addition of 80 mM galactosamine, which reverses coaggregation, mildly reduced adhesion to glass but inhibited the interaction and attachment to glass-surface-attached M. luteus 2.13 cells. As opposed to wild-type coaggregating cells, coaggregation-deficient S. natatoria 2.1COGgfp variant cells were retarded in colonizing glass and did not interact with glass-surface-attached M. luteus 2.13 cells. To determine if coaggregation enhances biofilm growth and expansion, viable coaggregating S. natatoria 2.1gfp cells or the coaggregation-deficient variant S. natatoria 2.1COGgfp cells were coinoculated in flow cells with viable M. luteus 2.13 cells and allowed to grow together for 96 h. Coaggregating S. natatoria 2.1gfp cells outcompeted M. luteus 2.13 cells, and 96-h biofilms were composed predominantly of S. natatoria 2.1gfp cells. Conversely, when coaggregation-deficient S. natatoria 2.1COGgfp cells were coinoculated with M. luteus 2.13 cells, the 96-h biofilm contained few coaggregation-deficient S. natatoria 2.1 cells. Thus, coaggregation promotes biofilm integration by facilitating attachment to partner species and likely contributes to the expansion of coaggregating S. natatoria 2.1 populations in dual-species biofilms through competitive interactions.
Contribution of Dry Needling to Individualized Physical Therapy Treatment of Shoulder Pain: A Randomized Clinical Trial

• STUDY DESIGN: Multicenter, parallel randomized clinical trial. • BACKGROUND: Myofascial trigger points (MTrPs) are implicated in shoulder pain and functional limitations. An intervention intended to treat MTrPs is dry needling. • OBJECTIVES: To investigate the effectiveness of dry needling in addition to evidence‐based personalized physical therapy treatment in the treatment of shoulder pain. • METHODS: One hundred twenty patients with nonspecific shoulder pain were randomly allocated into 2 parallel groups: (1) personalized, evidence‐based physical therapy treatment; and (2) trigger point dry needling in addition to personalized, evidence‐based physical therapy treatment. Patients were assessed at baseline, posttreatment, and 3‐month follow‐up. The primary outcome measure was pain assessed by a visual analog scale at 3 months, and secondary variables were joint range‐of‐motion limitations, Constant‐Murley score for pain and function, and number of active MTrPs. Clinical efficacy was assessed using intention‐to‐treat analysis. • RESULTS: Of the 120 enrolled patients, 63 were randomly assigned to the control group and 57 to the intervention group. There were no significant differences in outcome between the 2 treatment groups. Both groups showed improvement over time. • CONCLUSION: Dry needling did not offer benefits in addition to personalized, evidence‐based physical therapy treatment for patients with nonspecific shoulder pain. • LEVEL OF EVIDENCE: Therapy, level 1b. Registered February 11, 2009 at www.isrctn. com (ISRCTN30907460).
Decentralized Output-Feedback Neural Control for Systems With Unknown Interconnections

An adaptive backstepping neural-network control approach is extended to a class of large-scale nonlinear output-feedback systems with completely unknown and mismatched interconnections. The novel contribution is to remove the common assumptions on interconnections such as matching condition, bounded by upper bounding functions. Differentiation of the interconnected signals in backstepping design is avoided by replacing the interconnected signals in neural inputs with the reference signals. Furthermore, two kinds of unknown modeling errors are handled by the adaptive technique. All the closed-loop signals are guaranteed to be semiglobally uniformly ultimately bounded, and the tracking errors are proved to converge to a small residual set around the origin. The simulation results illustrate the effectiveness of the control approach proposed in this correspondence.
Resilient Randomized Quantized Consensus

We consider the problem of multiagent consensus where some agents are subject to faults/attacks and might make updates arbitrarily. The network consists of agents taking integer-valued (i.e., quantized) states under directed communication links. The goal of the healthy normal agents is to form consensus in their state values, which may be disturbed by the non-normal, malicious agents. We develop update schemes to be equipped by the normal agents whose interactions are asynchronous and subject to nonuniform and time-varying time delays. In particular, we employ a variant of the so-called mean subsequence reduced algorithms, which have been long studied in computer science, where each normal agent ignores extreme values from its neighbors. We solve the resilient quantized consensus problems in the presence of totally/locally bounded adversarial agents and provide necessary and sufficient conditions in terms of the connectivity notion of graph robustness. Furthermore, it will be shown that randomization is essential both in quantization and in the updating times when normal agents interact in an asynchronous manner. The results are examined through a numerical example.
Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in Bone Tissue Regeneration

Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc–Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc–Gel–MTN assemblies were incubated in simulated body fluid (SBF) to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp). The formed Fuc–Gel–MTN–beta–TCP/HAP scaffolds were found to display an average Young’s Modulus value of 0.32 GPa (n = 5) with an average surface roughness of 91 nm. Rheological studies show that the biomineralized scaffold exhibited higher storage and loss modulus compared to the composites formed before biomineralization. Thermal phase changes were studied through DSC and TGA analysis. XRD and EDS analyses indicated a biphasic mixture of β-tricalcium phosphate and hydroxyapatite and the composition of the scaffold. The scaffold promoted cell proliferation, differentiation and displayed actin stress fibers indicating the formation of cell-scaffold matrices in the presence of MT3C3-E1 mouse preosteoblasts. Osteogenesis and mineralization were found to increase with Fuc–Gel–MTN–beta–TCP/HAP scaffolds. Thus, we have developed a novel scaffold for possible applications in bone tissue engineering.
Divergent Effects of miR‐181 Family Members on Myocardial Function Through Protective Cytosolic and Detrimental Mitochondrial microRNA Targets

Background MicroRNA (miRNA) is a type of noncoding RNA that can repress the expression of target genes through posttranscriptional regulation. In addition to numerous physiologic roles for miRNAs, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported that nuclear encoded microRNA (miR‐181c) is present in heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating mitochondrial gene expression. Methods and Results To investigate further how the miR‐181 family affects the heart, we suppressed miR‐181 using a miR‐181‐sponge containing 10 repeated complementary miR‐181 “seed” sequences and generated a set of H9c2 cells, a cell line derived from rat myoblast, by stably expressing either a scrambled or miR‐181‐sponge sequence. Sponge‐H9c2 cells showed a decrease in reactive oxygen species production and reduced basal mitochondrial respiration and protection against doxorubicin‐induced oxidative stress. We also found that miR‐181a/b targets phosphatase and tensin homolog (PTEN), and the sponge‐expressing stable cells had increased PTEN activity and decreased PI3K signaling. In addition, we have used miR‐181a/b−/− and miR‐181c/d−/− knockout mice and subjected them to ischemia‐reperfusion injury. Our results suggest divergent effects of different miR‐181 family members: miR‐181a/b targets PTEN in the cytosol, resulting in an increase in infarct size in miR‐181a/b−/− mice due to increased PTEN signaling, whereas miR‐181c targets mt‐COX1 in the mitochondria, resulting in decreased infarct size in miR‐181c/d−/− mice. Conclusions The miR‐181 family alters the myocardial response to oxidative stress, notably with detrimental effects by targeting mt‐COX1 (miR‐181c) or with protection by targeting PTEN (miR‐181a/b).
Dynamic Background Segmentation for Remote Reference Image Updating within Motion Detection JPEG2000

We present in this paper a new system based on motion JPEG2000 intended for road surveillance application. The system uses a reference image and consists in 4 processing steps, namely initialization phase where the first reference image is built, reference estimation, motion segmentation (foreground extraction, ROI mask), and JPEG2000 coding. A first order recursive filter is used to build a reference image that corresponds to the background image. The obtained background is sent to the decoder once for all. The reference image at the coder side is estimated according to a Gaussian mixture model. The remote reference image is updated when specific conditions are met. The updating remote reference is triggered according to the states of mobile objects in the scene (no, few or lot of mobiles). The motion detection given by classical background subtraction technique is performed in order to extract a binary mask. The motion mask gives the region of interest of the system. The JPEG2000 image coded with a ROI option is sent towards the decoder. The decoder receives, decodes the image and builds the implicit binary ROI mask. Then, the decoder builds the displayed image using the reference image, the current image and the mask.
Crevice Corrosion of Ball Bond Intermetallics of Cu and Ag Wire

In this work we present results, both experimental and theoretical, related to corrosion of intermetallic layers that are formed at the interface between the bond pad and the bond ball. Aluminum smear adjacent to the bond ball leads to an initial crevice. Due to a galvanic corrosion process an oxygen deficit in the crevice might occur. Numerical simulations show that in the absence of oxygen the anodic oxidation process will become dominant, which leads to an acidification of the crevice, and finally to an enrichment in the chloride concentration. These conditions will highly accelerate the corrosion process of the intermetallic layer, and thus a growth of the initial crevice, and eventually to complete ball lift during reliability tests.
Nonanatomic Anterior Cruciate Ligament Reconstruction With Double-Stranded Semitendinosus Grafts in Children With Open Physes

Background: Nonanatomic anterior cruciate ligament (ACL) reconstruction (ACLR) with double-stranded semitendinosus grafts in children with open physes has been described as a successful surgical technique in short-term follow-up clinical reports. Purpose: To evaluate the clinical outcomes of nonanatomic ACLR in children with open physes and a minimum of 15 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: Twelve patients with an average age of 10.7 years (range, 8.3-12.4 years) underwent ACLR between 1991 and 1998. All patients were classified as Tanner development stage 2 or lower. The surgical technique involved transphyseal tibial tunnel drilling and over-the-top (OTT) femoral fixation using a double-stranded graft for all patients. Clinical outcomes were evaluated in terms of the manual Lachman test, pivot-shift test, return to sports activity, and International Knee Documentation Committee (IKDC) score at the end of growth and at a minimum 15-year follow-up (range, 15-22 years). Results: No clinically significant growth disturbance was observed. Ten patients had a grade A IKDC score, and 2 patients had a grade B IKDC score at the end of growth. There was no progression of laxity or modification of knee stability with growth. Three patients (25%) had ACL reruptures during sports activities after growth plate closure. All patients with reruptured ACLs underwent additional reconstructive surgery. Conclusion: Anterior cruciate ligament reconstruction using the OTT technique in the femur and the transphyseal technique in the tibia produces good results with regard to growth plate closure but a high failure rate in adulthood.
pfSNP: An integrated potentially functional SNP resource that facilitates hypotheses generation through knowledge syntheses

Currently, >14,000,000 single nucleotide polymorphisms (SNPs) are reported. Identifying phenotype‐affecting SNPs among these many SNPs pose significant challenges. Although several Web resources are available that can inform about the functionality of SNPs, these resources are mainly annotation databases and are not very comprehensive. In this article, we present a comprehensive, well‐annotated, integrated pfSNP (potentially functional SNPs) Web resource (http://pfs.nus.edu.sg/), which is aimed to facilitate better hypothesis generation through knowledge syntheses mediated by better data integration and a user‐friendly Web interface. pfSNP integrates >40 different algorithms/resources to interrogate >14,000,000 SNPs from the dbSNP database for SNPs of potential functional significance based on previous published reports, inferred potential functionality from genetic approaches as well as predicted potential functionality from sequence motifs. Its query interface has the user‐friendly “auto‐complete, prompt‐as‐you‐type” feature and is highly customizable, facilitating different combination of queries using Boolean‐logic. Additionally, to facilitate better understanding of the results and aid in hypotheses generation, gene/pathway‐level information with text clouds highlighting enriched tissues/pathways as well as detailed‐related information are also provided on the results page. Hence, the pfSNP resource will be of great interest to scientists focusing on association studies as well as those interested to experimentally address the functionality of SNPs. Hum Mutat 32:19–24, 2011. © 2010 Wiley‐Liss, Inc.
Validation of the Tiba Medical Ambulo 2400 ambulatory blood pressure monitor to the ISO Standard and BHS protocol

ObjectiveWe evaluated the Tiba Medical Ambulo 2400 ambulatory blood pressure monitor accuracy by both the International Standards Organization (ISO) Standard and the British Hypertension Society (BHS) protocol. MethodsWe tested children, adolescents, and adults. The requirements for both ISO and BHS were completed for 85 individuals each. ResultsThe Ambulo 2400 passed both ISO and BHS criteria. For ISO method 1, the mean±SD for the difference between device and manual systolic blood pressure (SBP) was −1.8±6.5 mmHg; for diastolic blood pressure (DBP) the values were 0.7±7.3 mmHg. For the method 2 analyses, the differences were −1.8±4.7 and 0.7±6.3 mmHg for SBP and DBP, respectively. The percentage of differences within 5, 10, and 15 mmHg were 60, 86, and 98% for SBP, and 60, 85, and 96% for DBP. ConclusionThe Ambulo 2400 passed all phases of the ISO testing and achieved an A grade for both SBP and DBP per BHS analyses. There was no decrease in accuracy in either high or low BP ranges. The Ambulo 2400 integrates activity monitoring for assigning actual awake and asleep times. There are software features that are particularly beneficial to monitor children and adolescents.