Deswelling Induced Morphological Changes in Dual pH and Temperature Responsive Ultra-Low Crosslinked Poly (N-isopropyl acrylamide)-co-Acrylic Acid Microgels

Poly(N-isopropylacrylamide) microgels prepared without exogenous cross-linker are extremely “soft” as a result of their very low cross-linking density, with network connectivity arising only from the self-crosslinking of pNIPAm chains. As a result of this extreme softness, our group and others have taken interest in using these materials in a variety of bioengineering applications, while also pursuing studies of their fundamental properties. Here, we report deswelling triggered structural changes in poly(N-isopropylacrylamide-co-acrylic acid) (ULC10AAc) microgels prepared by precipitation polymerization. Dynamic light scattering suggests that the deswelling of these particles not only depends on the collapse of the pNIPAm chains but is also influenced by the ionization state of the acrylic acid moieties present in the copolymer. The ULC10AAc microgel behaves like a traditional cross-linked pNIPAm microgel at pH 3.5, showing a sharp decrease in the hydrodynamic diameter around the lower critical solution temperature (LCST) of pNIPAm. As the pH is increased to 4.5, we observe multiple transitions in the deswelling curve, suggesting inhomogeneity in the structure and/or composition of the microgels. At pH 6.5, the microgels cease to be thermoresponsive over the studied temperature range due to increased charge repulsion between the fully deprotonated AAc groups and an increase in gel osmotic pressure due to solvated counterion ingress. Atomic force microscopy images of particles deposited at different temperatures reveal a temperature-induced morphological change, with punctate structures forming inside microgels at pH 4.5 and 6.5 and temperature above the gel volume phase transition temperature (VPTT)

Automatic detection of complete and measurable cardiac cycles in antenatal pulsed-wave Doppler signals

Background and objective: Pulsed-wave Doppler (PWD) echocardiography is the primary tool for antenatal cardiological diagnosis. Based on it, different measurements and validated reference parameters can be extracted. The automatic detection of complete and measurable cardiac cycles would represent a useful tool for the quality assessment of the PWD trace and the automated analysis of long traces. Methods: This work proposes and compares three different algorithms for this purpose, based on the preliminary extraction of the PWD velocity spectrum envelopes: template matching, supervised classification over a reduced set of relevant waveshape features, and supervised classification over the whole waveshape potentially representing a cardiac cycle. A custom dataset comprising 43 fetal cardiac PWD traces (174,319 signal segments) acquired on an apical five-chamber window was developed and used for the assessment of the different algorithms. Results: The adoption of a supervised classifier trained with the samples representing the upper and lower envelopes of the PWD, with additional features extracted from the image, achieved significantly better results (p < 0.0001) than the other algorithms, with an average accuracy of 98% ± 1% when using an SVM classifier and a leave-one-subject-out cross-validation. Further, the robustness of the results with respect to the classifier model was proved. Conclusions: The results reveal excellent detection performance, suggesting that the proposed approach can be adopted for the automatic analysis of long PWD traces or embedded in ultrasound machines as a first step for the extraction of measurements and reference clinical parameters

A non-invasive multimodal foetal ECG–Doppler dataset for antenatal cardiology research

Non-invasive foetal electrocardiography (fECG) continues to be an open topic for research. The development of standard algorithms for the extraction of the fECG from the maternal electrophysiological interference is limited by the lack of publicly available reference datasets that could be used to benchmark different algorithms while providing a ground truth for foetal heart activity when an invasive scalp lead is unavailable. In this work, we present the Non-Invasive Multimodal Foetal ECG-Doppler Dataset for Antenatal Cardiology Research (NInFEA), the first open-access multimodal early-pregnancy dataset in the field that features simultaneous non-invasive electrophysiological recordings and foetal pulsed-wave Doppler (PWD). The dataset is mainly conceived for researchers working on fECG signal processing algorithms. The dataset includes 60 entries from 39 pregnant women, between the 21st and 27th week of gestation. Each dataset entry comprises 27 electrophysiological channels (2048 Hz, 22 bits), a maternal respiration signal, synchronised foetal trans-abdominal PWD and clinical annotations provided by expert clinicians during signal acquisition. MATLAB snippets for data processing are also provided

Annotated real and synthetic datasets for non-invasive foetal electrocardiography post-processing benchmarking

Non-invasive foetal electrocardiography (fECG) can be obtained at different gestational ages by means of surface electrodes applied on the maternal abdomen. The signal-to-noise ratio (SNR) of the fECG is usually low, due to the small size of the foetal heart, the foetal-maternal compartment, the maternal physiological interferences and the instrumental noise. Even after powerful fECG extraction algorithms, a post-processing step could be required to improve the SNR of the fECG signal. In order to support the researchers in the field, this work presents an annotated dataset of real and synthetic signals, which was used for the study “Wavelet Denoising as a Post-Processing Enhancement Method for Non-Invasive Foetal Electrocardiography” [1]. Specifically, 21 15 s-long fECG, dual-channel signals obtained by multi-reference adaptive filtering from real electrophysiological recordings were included. The annotation of the foetal R peaks by an expert cardiologist was also provided. Recordings were performed on 17 voluntary pregnant women between the 21st and the 27th week of gestation. The raw recordings were also included for the researchers interested in applying a different fECG extraction algorithm. Moreover, 40 10 s-long synthetic non-invasive fECG were provided, simulating the electrode placement of one of the abdominal leads used for the real dataset. The annotation of the foetal R peaks was also provided, as generated by the FECGSYN tool used for the signals’ creation. Clean fECG signals were also included for the computation of indexes of signal morphology preservation. All the signals are sampled at 2048 Hz. The data provided in this work can be used as a benchmark for fECG post-processing techniques but can also be used as raw signals for researchers interested in foetal QRS detection algorithms and fECG extraction methods

Wavelet denoising as a post-processing enhancement method for non-invasive foetal electrocardiography

Background and Objective: The detection of a clean and undistorted foetal electrocardiogram (fECG) from non-invasive abdominal recordings is an open research issue. Several physiological and instrumental noise sources hamper this process, even after that powerful fECG extraction algorithms have been used. Wavelet denoising is widely used for the improvement of the SNR in biomedical signal processing. This work aims to systematically assess conventional and unconventional wavelet denoising approaches for the post-processing of fECG signals by providing evidence of their effectiveness in improving fECG SNR while preserving the morphology of the signal of interest. Methods: The stationary wavelet transform (SWT) and the stationary wavelet packet transform (SWPT) were considered, due to their different granularity in the sub-band decomposition of the signal. Three thresholds from the literature, either conventional (Minimax and Universal) and unconventional, were selected. To this aim, the unconventional one was adapted for the first time to SWPT by trying different approaches. The decomposition depth was studied in relation to the characteristics of the fECG signal. Synthetic and real datasets, publicly available for benchmarking and research, were used for quantitative analysis in terms of noise reduction, foetal QRS detection performance and preservation of fECG morphology. Results: The adoption of wavelet denoising approaches generally improved the SNR. Interestingly, the SWT methods outperformed the SWPT ones in morphology preservation (p<0.04) and SNR (p<0.0003), despite their coarser granularity in the sub-band analysis. Remarkably, the Han et al. threshold, adopted for the first time for fECG processing, provided the best quality improvement (p<0.003). Conclusions: The findings of our systematic analysis suggest that particular care must be taken when selecting and using wavelet denoising for non-invasive fECG signal post-processing. In particular, despite the general noise reduction capability, signal morphology can be significantly altered on the basis of the parameterization of the wavelet methods. Remarkably, the adoption of a finer sub-band decomposition provided by the wavelet packet was not able to improve the quality of the processing

Imaging findings of hepatic focal nodular hyperplasia in men and women: are they really different?

Purpose This study was undertaken to compare the imaging findings of focal nodular hyperplasia (FNH) in men and women, as seen on multidetector computed tomography (MDCT), magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS). Materials and methods Two radiologists reviewed 195 imaging studies (17 MDCT, 81 MRI and 97 CEUS examinations) pertaining to 111 FNHs (mean size 3 cm) in 91 patients (mean age 39 years). For each lesion, the readers assessed size, location, echogenicity, attenuation, or signal intensity in comparison with adjacent liver parenchyma on both unenhanced and postcontrast images. Results Eighty-nine FNHs (mean size 3.1 cm) were observed in 73 women (mean age 37.9 years) and 22 FNHs (mean size 2.7 cm) in 18 men (mean age 41.2 years). No statistically significant differences were found between men and women in terms of age, FNH lesions per patient (1.22 and 1.21, respectively), size, baseline and enhancement pattern on MRI, CEUS and MDCT (p < 0.05). A central scar in FNHs was depicted in 4/18 (22.2 %) men and 16/63 (25.4 %) women on MRI (p < 0.05), and in 1/2 (50 %) men and 7/15 (46.7 %) women on MDCT (p < 0.05), whereas a spoke-wheel pattern, central scar, and/or feeding vessel were seen in 5/17 (29.4 %) men and 22/80 (27.5 %) women on CEUS (p < 0.05). Conclusions Our results did not show any differences in imaging features, age of occurrence and size of FNH between men and women

Impact of pulsed-wave-Doppler velocity-envelope tracing techniques on classification of complete fetal cardiac cycles

Fetal echocardiography is an operator-dependent examination technique requiring a high level of expertise. Pulsed-wave Doppler (PWD) is often used as a reference for the mechanical activity of the heart, from which several quantitative parameters can be extracted. These aspects suggest the development of software tools that can reliably identify complete and clinically meaningful fetal cardiac cycles that can enable their automatic measurement. Several scientific works have addressed the tracing of the PWD velocity envelope. In this work, we assess the different steps involved in the signal processing chains that enable PWD envelope tracing. We apply a supervised classifier trained on envelopes traced by different signal processing chains for distinguishing complete and measurable PWD heartbeats from incomplete or malformed ones, which makes it possible to determine the impact of each of the different processing steps on the detection accuracy. In this study, we collected 43 images and labeled 174,319 PWD segments from 25 pregnant women volunteers. By considering seven envelope tracing techniques and the 23 different processing steps involved in their implementation, the results of our study reveal that, compared to the steps investigated in most other works, those that achieve binarisation and envelope extraction are significantly more important (p &lt; 0.05). The best approaches among those studied enabled greater than 98% accuracy on our large manually annotated dataset

Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype

Risk Factors and Outcomes of Candidemia Caused by Biofilm-Forming Isolates in a Tertiary Care Hospital

Very few data exist on risk factors for developing biofilm-forming Candida bloodstream infection (CBSI) or on variables associated with the outcome of patients treated for this infection. METHODS AND FINDINGS: We identified 207 patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming Candida isolates were recovered. A case-case-control study to identify risk factors and a cohort study to analyze outcomes were conducted. In addition, two sub-groups of case patients were analyzed after matching for age, sex, APACHE III score, and receipt of adequate antifungal therapy. Independent predictors of biofilm-forming CBSI were presence of central venous catheter (odds ratio [OR], 6.44; 95% confidence interval [95% CI], 3.21-12.92) or urinary catheter (OR, 2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI, 2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital mortality, post-CBSI hospital length of stay (LOS) (calculated only among survivors), and costs of antifungal therapy were significantly greater among patients infected by biofilm-forming isolates than those infected by non-biofilm-forming isolates. Among biofilm-forming CBSI patients receiving adequate antifungal therapy, those treated with highly active anti-biofilm (HAAB) agents (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was confirmed when this analysis was conducted only among survivors. After matching, all the outcomes were still favorable for patients with non-biofilm-forming CBSI. Furthermore, the biofilm-forming CBSI was significantly associated with a matched excess risk for hospital death of 1.77 compared to non-biofilm-forming CBSI. CONCLUSIONS: Our data show that biofilm growth by Candida has an adverse impact on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for those CBSI patients who received HAAB antifungal therapy