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Reflectance diffuse optical tomography (rDOT) of brain function is limited by its high sensitivity to the superficial tissues (i.e., the scalp and skull) and by its severe decrease in measurement sensitivity with increased depth. Significant interference in rDOT results from spontaneous fluctuations that are embedded in both the superficial tissues and brain, such as arterial pulsation and vasomotion. In this study, first we investigate coherence and phase shift of the spontaneous fluctuations in the resting state, within the superficial tissues and at various depths of the brain, respectively. We demonstrate that the spontaneous fluctuations originating from arterial pulsations (~ 1 Hz) are spatially global and temporally coherent, while the fluctuations originating from vasomotion (~ 0.1 Hz) tend to have less coherence with increased depth. Second, adaptive cancellation of spontaneous fluctuations with a frequency-specific strategy is utilized and validated in both resting and activation (evoked by a finger-tapping task) states. Third, improved depth localization of motor activation in reconstructed rDOT images is achieved by combining adaptive cancellation with a depth compensation algorithm that we recently reported. [ABSTRACT FROM PUBLISHER]

BACKGROUND: The role of capsule endoscopy (CE) in the diagnosis of active mild-to-moderate GI bleeding (GIB) immediately after a negative EGD and ileocolonoscopy has not been prospectively evaluated. OBJECTIVE: To estimate the diagnostic yield and clinical significance of CE in patients with acute, obscure, overt, mild-to-moderate GIB. DESIGN: A single-center prospective study. PATIENTS: During a 3-year period, 573 patients admitted to the hospital with acute mild-to-moderate GIB were included in this study. Among them, 37 patients (6.5%) with negative endoscopic findings, after urgent upper- and lower-GI endoscopies, underwent CE within the first 48 hours to identify the source of bleeding. RESULTS: CE revealed active bleeding in 34 patients and a diagnostic yield of 91.9%, including angiodysplasias in 18 patients, ulcers in 3 patients, and tumors in 2 patients. In the remaining 11 patients (32%), CE revealed the site of bleeding: distal duodenum in 1 case (9%), jejunum in 6 cases (54%), ileum in 2 cases (18%), and cecum in 2 cases (18%). From the 37 bleeders, 16 were managed conservatively, 14 endoscopically, and 7 surgically. During a 12-month follow-up period, bleeding recurrence was observed in 5 of 32 (15.6%). LIMITATIONS: This study had a limited number of patients. CONCLUSIONS: CE appeared to have a high diagnostic yield in patients with acute, mild-to-moderate, active hemorrhage of obscure origin when performed in the hospital after a negative standard endoscopic evaluation and has important clinical value in guiding medical management. [ABSTRACT FROM AUTHOR]

Purpose: To present our experience performing percutaneous cholangioscopy in the management of 25 patients with biliary disease.Methods: During the last 3 years, 26 percutaneous cholangioscopies were performed in 25 patients with common bile duct disease (n = 16), intrahepatic ducts disease (n = 6), and gallbladder disease (n = 4). Our patient population group included seven with common bile duct stones, three with intrahepatic lithiasis, and eight with benign strictures (six iatrogenic and two postinflammatory). In four patients malignancy was to be excluded, in two the tumor extent was to be evaluated, whereas in one case the correct placement of a metallic stent needed to be controlled. A 9.9 Fr flexible endoscope URF-P (Olympus, 1.2 mm working channel, 70-cm length) was used.Results: In total, percutaneous cholangioscopy answered 30 diagnostic questions, was technically helpful in 19 cases (performing lithotripsy or biopsy or guiding a wire), and of therapeutic help in 12 (performing stone retrieval). In 24 of 26 cases the therapeutic decision and the patient management changed because of the findings or because of the help of the method. In two cases biliary intervention failed to treat the cause of the disease. No major complication due to the use of the endoscopy was noted.Conclusions: Percutaneous cholangioscopy is a very useful tool in the management of patients with biliary disease. The method can help in diagnosis, in performing complex interventional procedures, and in making or changing therapeutic decisions. [ABSTRACT FROM AUTHOR]

The rapidly advancing field of nanotechnology is driving the development of precise sensing methods at the nanoscale, with solid-state nanopores emerging as promising tools for biomolecular sensing. This study investigates the increased sensitivity of solid-state nanopores achieved by integrating DNA origami structures, leading to the improved analysis of protein translocations. Using holo human serum transferrin (holo-hSTf) as a model protein, we compared hybrid nanopores incorporating DNA origami with open solid-state nanopores. Results show a significant enhancement in holo-hSTf detection sensitivity with DNA origami integration, suggesting a unique role of DNA interactions beyond confinement. This approach holds potential for ultrasensitive protein detection in biosensing applications, offering advancements in biomedical research and diagnostic tool development for diseases with low-abundance protein biomarkers. Further exploration of origami designs and nanopore configurations promises even greater sensitivity and versatility in the detection of a wider range of proteins, paving the way for advanced biosensing technologies.

Dipole localization, a fundamental challenge in electromagnetic source imaging, inherently constitutes an optimization problem aimed at solving the inverse problem of electric current source estimation within the human brain. The accuracy of dipole localization algorithms is contingent upon the complexity of the forward model, often referred to as the head model, and the signal-to-noise ratio (SNR) of measurements. In scenarios characterized by low SNR, often corresponding to deep-seated sources, existing optimization techniques struggle to converge to global minima, thereby leading to the localization of dipoles at erroneous positions, far from their true locations. This study presents a novel hybrid algorithm that combines simulated annealing with the traditional quasi-Newton optimization method, tailored to address the inherent limitations of dipole localization under low-SNR conditions. Using a realistic head model for both electroencephalography (EEG) and magnetoencephalography (MEG), it is demonstrated that this novel hybrid algorithm enables significant improvements of up to 45% in dipole localization accuracy compared to the often-used dipole scanning and gradient descent techniques. Localization improvements are not only found for single dipoles but also in two-dipole-source scenarios, where sources are proximal to each other. The novel methodology presented in this work could be useful in various applications of clinical neuroimaging, particularly in cases where recordings are noisy or sources are located deep within the brain.

Background: Pulse oximeters work within the red-infrared wavelengths. Therefore, these oximeters produce erratic results in dark-skinned subjects and in subjects with cold extremities. Pulse oximetry is routinely performed in patients with fever; however, an elevation in body temperature decreases the affinity of hemoglobin for oxygen, causing a drop in oxygen saturation or oxyhemoglobin concentrations., Objective: We aimed to determine whether our new investigational device, the Shani device or SH1 (US Patent 11191460), detects a drop in oxygen saturation or a decrease in oxyhemoglobin concentrations., Methods: An observational study (phase 1) was performed in two separate groups to validate measurements of hemoglobin and oxygen concentrations, including 39 participants recruited among current university students and staff aged 20-40 years. All volunteers completed baseline readings using the SH1 device and the commercially available Food and Drug Administration-approved pulse oximeter Masimo. SH1 uses two light-emitting diodes in which the emitted wavelengths match with absorption peaks of oxyhemoglobin (hemoglobin combined with oxygen) and deoxyhemoglobin (hemoglobin without oxygen or reduced hemoglobin). Total hemoglobin was calculated as the sum of oxyhemoglobin and deoxyhemoglobin. Subsequently, 16 subjects completed the "heat jacket study" and the others completed the "blood donation study." Masimo was consistently used on the finger for comparison. The melanin level was accounted for using the von Luschan skin color scale (VLS) and a specifically designed algorithm. We here focus on the results of the heat jacket study, in which the subject wore a double-layered heated jacket and pair of trousers including a network of polythene tubules along with an inlet and outlet. Warm water was circulated to increase the body temperature by 0.5-0.8 °C above the baseline body temperature. We expected a slight drop in oxyhemoglobin concentrations in the heating phase at the tissue level., Results: The mean age of the participants was 24.1 (SD 0.8) years. The skin tone varied from 12 to 36 on the VLS, representing a uniform distribution with one-third of the participants having fair skin, brown skin, and dark skin, respectively. Using a specific algorithm and software, the reflection ratio for oxyhemoglobin was displayed on the screen of the device along with direct hemoglobin values. The SH1 device picked up more minor changes in oxyhemoglobin levels after a change in body temperature compared to the pulse oximeter, with a maximum drop in oxyhemoglobin concentration detected of 6.5% and 2.54%, respectively., Conclusions: Our new investigational device SH1 measures oxygen saturation at the tissue level by reflectance spectroscopy using green wavelengths. This device fared well regardless of skin color. This device can thus eliminate racial disparity in these key biomarker assessments. Moreover, since the light is shone on the wrist, SH1 can be readily miniaturized into a wearable device., (©Sanjay Gokhale, Vinoop Daggubati, Georgios Alexandrakis. Originally published in JMIR Biomedical Engineering (http://biomsedeng.jmir.org), 27.03.2024.)

Bimodal optical-electrical data generated when a 20 nm diameter silica (SiO 2 ) nanoparticle was trapped by a plasmonic nanopore sensor were simulated using Multiphysics COMSOL and compared with sensor measurements for closely matching experimental parameters. The nanosensor, employed self-induced back action (SIBA) to optically trap nanoparticles in the center of a double nanohole (DNH) structure on top a solid-state nanopores (ssNP). This SIBA actuated nanopore electrophoresis (SANE) sensor enables simultaneous capture of optical and electrical data generated by several underlying forces acting on the trapped SiO 2 nanoparticle: plasmonic optical trapping, electroosmosis, electrophoresis, viscous drag, and heat conduction forces. The Multiphysics simulations enabled dissecting the relative contributions of those forces acting on the nanoparticle as a function of its location above and through the sensor's ssNP. Comparisons between simulations and experiments demonstrated qualitative similarities in the optical and electrical time-series data generated as the nanoparticle entered and exited from the SANE sensor. These experimental parameter-matched simulations indicated that the competition between optical and electrical forces shifted the trapping equilibrium position close to the top opening of the ssNP, relative to the optical trapping force maximum that was located several nm above. The experimentally estimated minimum for the optical force needed to trap a SiO 2 nanoparticle was consistent with corresponding simulation predictions of optical-electrical force balance. The comparison of Multiphysics simulations with experiments improves our understanding of the interplay between optical and electrical forces as a function of nanoparticle position across this plasmonic nanopore sensor.

A nanopore device is capable of providing single-molecule level information of an analyte as they translocate through the sensing aperture-a nanometer-sized through-hole-under the influence of an applied electric field. In this study, a silicon nitride (Si x N y )-based nanopore was used to characterize the human serum transferrin receptor protein (TfR) under various applied voltages. The presence of dimeric forms of TfR was found to decrease exponentially as the applied electric field increased. Further analysis of monomeric TfR also revealed that its unfolding behaviors were positively dependent on the applied voltage. Furthermore, a comparison between the data of monomeric TfR and its ligand protein, human serum transferrin (hSTf), showed that these two protein populations, despite their nearly identical molecular weights, could be distinguished from each other by means of a solid-state nanopore (SSN). Lastly, the excluded volumes of TfR were experimentally determined at each voltage and were found to be within error of their theoretical values. The results herein demonstrate the successful application of an SSN for accurately classifying monomeric and dimeric molecules while the two populations coexist in a heterogeneous mixture., (© 2022 Wiley-VCH GmbH.)

We fabricated a novel single molecule nanosensor by integrating a solid-state nanopore and a double nanohole nanoaperture. The nanosensor employs Self-Induced Back-Action (SIBA) for optical trapping and enables SIBA-Actuated Nanopore Electrophoresis (SANE) for concurrent acquisition of bimodal optical and electrical signatures of molecular interactions. This work describes how to fabricate and use the SANE sensor to quantify antibody-ligand interactions. We describe how to analyze the bimodal optical-electrical data to improve upon the discrimination of antibody and ligand versus bound complex compared to electrical measurements alone. Example results for specific interaction detection are described for T-cell receptor-like antibodies (TCRmAbs) engineered to target peptide-presenting Major Histocompatibility Complex (pMHC) ligands, representing a model of target ligands presented on the surface of cancer cells. We also describe how to analyze the bimodal optical-electrical data to discriminate between specific and non-specific interactions between antibodies and ligands. Example results for non-specific interactions are shown for cancer-irrelevant TCRmAbs targeting the same pMHCs, as a control. These example results demonstrate the utility of the SANE sensor as a potential screening tool for ligand targets in cancer immunotherapy, though we believe that its potential uses are much broader., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Children with hemiplegic cerebral palsy (HCP) often show disturbances of somatosensation. Despite extensive evidence of somatosensory deficits, neurophysiological alterations associated with somatosensory deficits in children with HCP have not been elucidated. Here, we aim to assess phase synchrony within and between contralateral primary (S1) and secondary (S2) somatosensory areas in children with HCP. Intra-regional and inter-regional phase synchronizations within and between S1 and S2 were estimated from somatosensory evoked fields (SEFs) in response to passive pneumatic stimulation of contralateral upper extremities and recorded with pediatric magnetoencephalography (MEG) in children with HCP and typically developing (TD) children. We found aberrant phase synchronizations within S1 and between S1 and S2 in both hemispheres in children with HCP. Specifically, the less-affected (LA) hemisphere demonstrated diminished phase synchronizations after the stimulus onset up to ~120 ms compared to the more-affected (MA) hemisphere and the dominant hemisphere of TD children, while the MA hemisphere showed enhanced phase synchronizations after ~100 ms compared to the LA hemisphere and the TD dominant hemisphere. Our findings indicate abnormal somatosensory functional connectivity in both hemispheres of children with HCP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Interest in the design and manufacture of RNA and DNA aptamers as apta-biosensors for the early diagnosis of blood infections and other inflammatory conditions has increased considerably in recent years. The practical utility of these aptamers depends on the detailed knowledge about the putative interactions with their target proteins. Therefore, understanding the aptamer-protein interactions at the atomic scale can offer significant insights into the optimal apta-biosensor design. In this study, we consider one RNA and one DNA aptamer that were previously used as apta-biosensors for detecting the infection biomarker protein TNF- α , as an example of a novel computational workflow for selecting the aptamer candidate with the highest binding strength to a target. We combine information from the binding free energy calculations, molecular docking, and molecular dynamics simulations to investigate the interactions of both aptamers with TNF- α . The results reveal that the RNA aptamer has a more stable structure relative to the DNA aptamer. Interaction of aptamers with TNF- α does not have any negative effect on its structure. The results of molecular docking and molecular dynamics simulations suggest that the RNA aptamer has a stronger interaction with the protein. Also, these findings illustrate that basic residues of TNF- α establish more atomic contacts with the aptamers compared to acidic or pH-neutral ones. Furthermore, binding energy calculations show that the interaction of the RNA aptamer with TNF- α is thermodynamically more favorable. In total, the findings of this study indicate that the RNA aptamer is a more suitable candidate for using as an apta-biosensor of TNF- α and, therefore, of greater potential use for the diagnosis of blood infections. Also, this study provides more information about aptamer-protein interactions and increases our understanding of this phenomenon., Competing Interests: We declare no conflict of interest., (Copyright © 2021 Homayoun Asadzadeh et al.)