Brain-inspired computing with fluidic iontronic nanochannels.

The brain's remarkable and efficient information processing capability is driving research into brain-inspired (neuromorphic) computing paradigms. Artificial aqueous ion channels are emerging as an exciting platform for neuromorphic computing, representing a departure from conventional solid-state devices by directly mimicking the brain's fluidic ion transport. Supported by a quantitative theoretical model, we present easy-to-fabricate tapered microchannels that embed a conducting network of fluidic nanochannels between a colloidal structure. Due to transient salt concentration polarization, our devices are volatile memristors (memory resistors) that are remarkably stable. The voltage-driven net salt flux and accumulation, that underpin the concentration polarization, surprisingly combine into a diffusionlike quadratic dependence of the memory retention time on the channel length, allowing channel design for a specific timescale. We implement our device as a synaptic element for neuromorphic reservoir computing. Individual channels distinguish various time series, that together represent (handwritten) numbers, for subsequent in silico classification with a simple readout function. Our results represent a significant step toward realizing the promise of fluidic ion channels as a platform to emulate the rich aqueous dynamics of the brain.

Surface-dominant micro/nanofluidics for efficient green energy conversion.

Green energy conversion in aqueous systems has attracted considerable interest owing to the sustainable clean energy demand resulting from population and economic growth and urbanization, as well as the significant potential energy from water resources and other regenerative sources coupled with fluids. In particular, molecular motion based on intrinsic micro/nanofluidic phenomena at the liquid-solid interface (LSI) is crucial for efficient and sustainable green energy conversion. The electrical double layer is the main factor affecting transport, interaction between molecules and surfaces, non-uniform ion distribution, synthesis, stimulated reactions, and motion by external renewable resources in both closed nanoconfinement and open surfaces. In this review, we summarize the state-of-the-art progress in physical and chemical reaction-based green energy conversion in LSI, including nanoscale fabrication, key mechanisms, applications, and limitations for practical implementation. The prospects for resolving critical challenges in this field and inspiring other promising research areas in the infancy stage (studying chemical and biological dynamics at the single-molecule level and nanofluidic neuromorphic computing) are also discussed.

Successful Management of Refractory Kimura Disease with CVP Chemotherapy: A Case Report.

BACKGROUND Kimura disease is a rare, chronic inflammatory disorder typically presenting as a painless mass in the head or neck and associated with elevated serum immunoglobulin E and blood and tissue eosinophilia. Generally benign, its management is not well-defined, but corticosteroids are a common initial treatment. We detail a case of refractory Kimura disease successfully managed with CVP (Cyclophosphamide, Vincristine, Prednisone) chemotherapy and no recurrence during 6 rounds of treatment. CASE REPORT A 64-year-old woman, previously diagnosed with Kimura disease, returned to the hospital with upper eyelid ptosis. Upon examination, a solid mass was palpable in her left upper eyelid. Peripheral blood tests confirmed elevated IgE levels at 356.0 IU/ml. An excisional biopsy showed infiltration of lymphocytes and eosinophils, consistent with Kimura disease. Despite undergoing corticosteroid treatment, surgical debulking, radiation, and immunosuppressant therapy, her condition worsened. Concerns were raised due to imaging features suggestive of lymphoma, although no malignancy was evident in subsequent biopsies. It was decided to manage the disease using CVP chemotherapy, leading to significant symptom improvement. There have been no recurrences during the 12-month follow-up period. CONCLUSIONS Kimura disease is typically benign and responsive to treatment, but it often recurs and can progress. When symptoms are not controlled with conventional treatments, including corticosteroids, immunosuppressants, radiation, and surgical debulking, chemotherapy may be a reasonable option even when no definite signs of malignancy is identified. Further research is needed to explore the utility of CHOP and CVP in managing uncontrolled Kimura disease.

True Continuous Segment of Ossification of Posterior Longitudinal Ligament is Protective Against Postoperative Early Kyphosis Progression After Laminoplasty.

BACKGROUND AND OBJECTIVES: Ossification of the posterior longitudinal ligament (OPLL) is a potentially catastrophic disease. Laminoplasty (LP) is a common surgical intervention, but postoperative kyphosis progression is a major complication, for which various risk factors have been identified and used in surgical decision-making. Our focus is on the ability of OPLL with specific morphological traits, designated as the true continuous segment (TCS), to stabilize alignment and prevent postoperative kyphosis after LP. METHODS: This retrospective case-control study included patients who underwent cervical LP for OPLL treatment with a minimum 1-year follow-up. Demographic, operative, and radiographic parameters were analyzed. TCS is defined as a continuous segment of OPLL that spans the disk space more than half of the adjacent vertebral body height without crack, or OPLL segment attached to both upper and lower adjacent vertebral bodies by bridging, or obvious interbody autofusion, and is identified from preoperative computed tomography. A subgroup analysis for preoperatively lordotic patients, divided into 2 groups based on cervical alignment at the final follow-up, was conducted to identify risk factors for kyphosis progression. Difference analysis, linear regression analysis for loss of lordosis (LoL), and logistic regression analysis for kyphosis progression were used. RESULTS: A total of 84 patients were identified. Among them, 78 patients with preoperatively lordotic alignment were divided into 2 groups: those who maintained lordotic alignment (n = 60) and those who progressed to kyphosis (n = 18). Regression analyses revealed a significant protective effect of TCS count against LoL and postoperative kyphosis, with a TCS count of 3 or more conclusively preventing kyphosis (sensitivity 1.000, specificity 0.283, area under the curve 0.629). CONCLUSION: For patients with OPLL, TCS was shown to protect against the LoL after LP. Therefore, TCS should be identified and considered when planning surgical treatment for OPLL.

Multi-Layered Bipolar Ionic Diode Working in Broad Range Ion Concentration.

Ion current rectification (ICR) is the ratio of ion current by forward bias to backward bias and is a critical indicator of diode performance. In previous studies, there have been many attempts to improve the performance of this ICR, but there is the intrinsic problem for geometric changes that induce ionic rectification due to fabrication problems. Additionally, the high ICR could be achieved in the narrow salt concentration range only. Here, we propose a multi-layered bipolar ionic diode based on an asymmetric nanochannel network membrane (NCNM), which is realized by soft lithography and self-assembly of homogenous-sized nanoparticles. Owing to the freely changeable geometry based on soft lithography, the ICR performance can be explored according to the variation of microchannel shape. The presented diode with multi-layered configuration shows strong ICR performance, and in a broad range of salt concentrations (0.1 mM~100 mM), steady ICR performance. It is interesting to note that when each anion-selective (AS) and cation-selective (CS) NCNM volume was similar to each optimized volume in a single-layered device, the maximum ICR was obtained. Multi-physics simulation, which reveals greater ionic concentration at the bipolar diode junction under forward bias and less depletion under backward in comparison to the single-layer scenario, supports this tendency as well. Additionally, under different frequencies and salt concentrations, a large-area hysteresis loop emerges, which indicates fascinating potential for electroosmotic pumps, memristors, biosensors, etc.

Prognostic significance of thyroid-stimulating hormone receptor antibodies in moderate-to-severe graves' orbitopathy.

Design: Retrospective study. Purpose: The purpose of this retrospective study was to assess the changes in thyroid-stimulating hormone receptor (TSH-R) antibody levels following treatment in patients with moderate-to-severe and active Graves' orbitopathy (GO) and to investigate the correlation between these antibodies and treatment response. Methods: The subjects of this study comprised of patients newly diagnosed with moderate-to-severe and active GO within the age range of 19 to 79 years. All participants underwent intravenous methylprednisolone (IVMP) therapy for a duration of 12 weeks. Patients with a clinical activity score (CAS) decrease to or less than 3 and no symptom recurrence for at least 3months after the last dose of IVMP were classified as "Group 1". Those with a CAS equal to or greater than 4 were classified as "Group 2". TSH-R antibody levels were measured prior to and following IVMP treatment and treatment response was evaluated after the completion of IVMP therapy. All patients were monitored for a minimum of 6 months post-treatment, with ocular examinations and laboratory tests at the initial visit being included in the analysis. Results: The medical records of the 96 patients with GO were retrospectively reviewed. Seventy-five patients (78.1%) were response and 21 (21.9%) were non-responsive to IVMP treatment. A higher TSH-R antibody (TRAb) and thyroid-stimulating antibody (TSAb) following treatment were associated with a high risk of no treatment response (P = 0.017; P = 0.047, respectively). TRAb and TSAb levels before treatment were significantly related to TRAb and TSAb levels after treatment (P < 0.001, respectively). The cut-off values for the prediction of poor treatment response of the TRAb and TSAb before and after treatment were 8.305 IU/L, 5.035 IU/L and 449.5%, 361%, respectively (P = 0.027, P =0.001 and P = 0.136, P = 0.004, respectively). Conclusion: It was observed that elevated levels of TRAb and TSAb prior to IVMP treatment were positively correlated with post-treatment levels of these antibodies. Furthermore, in cases of non-response to IVMP therapy, a diminished decline in both antibodies was observed, and elevated levels of TRAb and TSAb post-treatment were found to be a significant predictor of poor treatment outcome. Measurement of TRAb and TSAb throughout the course of treatment in moderate-to-severe and active cases of GO may offer valuable insights into treatment prognosis and aid in the decision-making process regarding the potential need for increased IVMP dosage or alternative therapeutic strategies.

Factors related to steroid treatment responsiveness in thyroid eye disease patients and application of SHAP for feature analysis with XGBoost.

Introduction: The primary treatment for active thyroid eye disease (TED) is immunosuppressive therapy with intravenous steroids. In this study, we attempted to predict responsiveness to steroid treatment in TED patients using eXtreme Gradient Boosting (XGBoost). Factors associated with steroid responsiveness were also statistically evaluated. Methods: Clinical characteristics and laboratory results of 89 patients with TED who received steroid treatment were retrospectively reviewed. XGBoost was used to explore responsiveness to steroid treatment, and the diagnostic performance was evaluated. Factors contributing to the model output were investigated using the SHapley Additive exPlanation (SHAP), and the treatment response was investigated statistically using SPSS software. Results: The eXtra Gradient Boost model showed high performance, with an excellent accuracy of 0.861. Thyroid-stimulating hormone, thyroid-stimulating immunoglobulin (TSI), and low-density lipoprotein (LDL) cholesterol had the highest impact on the model. Multivariate logistic regression analysis showed that less extraocular muscle limitation and high TSI levels were associated with a high risk of poor intravenous methylprednisolone treatment response. As a result of analysis through SHAP, TSH, TSI, and LDL had the highest impact on the XGBoost model. Conclusion: TSI, extraocular muscle limitation, and LDL cholesterol levels may be useful in predicting steroid treatment response in patients with TED. In terms of machine learning, XGBoost showed relatively robust and reliable results for small datasets. The machine-learning model can assist in decision-making for further treatment of patients with TED.

Superior ophthalmic approach in carotid-cavernous fistula: current concepts in indications, surgical techniques, and case reviews.

Carotid-cavernous fistulas, characterized by abnormal arteriovenous communication within the cavernous sinus (CS), can be classified as direct or indirect. Direct fistulas are defined as a direct connection between the internal carotid artery (ICA) and CS, whereas indirect fistulas result from an abnormal connection between the CS and dural arterial branches. The first-line treatment for both types of fistulas is endovascular intervention, most commonly accomplished through the transarterial and transvenous approaches of the conventional pathway, including the ICA, inferior and superior petrosal sinuses, or basilar plexus. Nonetheless, a retrograde approach through the superior ophthalmic vein may be necessary for individuals in whom conventional endovascular treatment fails. Herein, the current principles of surgical indication and technique are presented, along with case studies.

Analyses of Pore-Size-Dependent Ionic Transport in Nanopores in the Presence of Concentration and Temperature Gradients.

Mass transport through nanopores occurs in various natural systems, including the human body. For example, ion transport across nerve cell membranes plays a significant role in neural signal transmission, which can be significantly affected by the electrolyte and temperature conditions. To better understand and control the underlying nanoscopic transport, it is necessary to develop multiphysical transport models as well as validate them using enhanced experimental methods for facile nanopore fabrication and precise nanoscale transport characterization. Here, we report a nanopore-integrated microfluidic platform to characterize ion transport in the presence of electrolyte and temperature gradients; we employ our previous self-assembled particle membrane (SAPM)-integrated microfluidic platform to produce various nanopores with different pore sizes. Subsequently, we quantify pore-size-dependent ionic transport by measuring the short circuit current (SCC) and open circuit voltage (OCV) across various nanopores by manipulating the electrolyte and temperature gradients. We establish three simple theoretical models that heavily depend on pore size, electrolyte concentration, and temperature and subsequently validate them with the experimental results. Finally, we anticipate that the results of this study would help clarify ion transport phenomena at low-temperature conditions, not only providing a fundamental understanding but also enabling practical applications of cryo-anesthesia in the near future.

Counting DNA molecules on a microchannel surface for quantitative analysis.

Microscopic visualization of DNA molecules is a simple, intuitive, and powerful method. Nonetheless, DNA-molecule quantification methods that employ microscopic visualization have not been reported so far. In this study, a new quantitative approach is presented that enables the counting of individual DNA molecules that have been rendered visible by fluorescence microscopy. Toward this, a microfluidic device was employed that directed DNA molecules into microchannels and deposited the molecules onto a positively charged surface. This microfluidic device had a vertically tapered channel inlet structure that prevented the accumulation of excess DNA molecules in the channel inlet while creating a tapering flow, thereby ensuring the even distribution of the DNA molecules in the microchannels. The channel heights and the density of positive charges on the surface were optimized for analysis. The linearity of this method with respect to the determination of the concentration of DNA in solutions was subsequently determined. The limit of detection was 0.48 fg/µL, which corresponds to 64 molecules of 7.25 kbp DNA in 1 µL of sample. This quantitative approach was finally used to count two types of plasmids co-transformed in an E. coli cell; a measurement that is typically considered challenging with gel electrophoresis.

Clinical Results According to Inferior Oblique Manipulation in Patients with Inferomedial Blowout Fracture Involving the Orbital Strut.

Background: Detachment of the inferior oblique muscle may be necessary under certain circumstances to repair a large inferomedial orbital fracture involving the orbital strut. This study aimed to evaluate the outcomes of patients who underwent surgeries with and without inferior oblique muscle reattachment after its detachment to repair the orbital wall fractures. Methods: Forty patients who underwent repair of combined floor and medial orbital wall fracture involving the orbital strut at a single tertiary institution between January 2014 and December 2020 were reviewed. Groups 1 and 2 comprised 20 patients each, who underwent surgery with inferior oblique muscle detachment without and with reattachment, respectively, and were followed up for at least 6 months postoperatively. Enophthalmos, Goldmann diplopia test, alignment test, ocular motility test, and orbital inferomedial angle ratio were the outcome measures. Results: Statistically significant improvement was observed in ocular motility, diplopia, and enophthalmos postoperatively at the 1- and 6-month follow-up (p < 0.01). The mean postoperative inferomedial angle ratio (102.28 ± 10.62%) was improved significantly compared with the preoperative inferomedial angle ratio (115.61 ± 4.38%) (p = 0.004) in all patients. After surgery, inferior oblique muscle underaction was observed in seven and six patients in groups 1 and 2, respectively, which was associated with preoperative extraocular movement limitation and strabismus. Two patients showed diplopia in both groups at the last follow-up; they had inferior oblique muscle underaction but no enophthalmos. Conclusion: Orbital fracture repair with or without inferior oblique muscle reattachment was clinically effective and safe; however, patients with preoperative strabismus and extraocular motility limitation should be informed of the increased risk of postoperative complications.

Ligamentum flavum hypertrophy significantly contributes to the severity of neurogenic intermittent claudication in patients with lumbar spinal canal stenosis.

Ligamentum flavum hypertrophy (LFH) is a known contributor to lumbar spinal canal stenosis (LSCS). However, the clinical significance and quantitative role of LFH compared to other components, such as disc bulging and facet hypertrophy, have not yet been examined. We investigated the correlation between the quantitative radiological factors, clinical symptoms, and outcomes in patients with LSCS. In total, 163 patients diagnosed with single-level (L4-L5) stenosis were included. The patients were divided into 2 groups according to claudication severity: >100 m for mild (n = 92) and < 100 m for severe (n = 71). The visual analog scale (VAS) was used to quantify back and leg pain, and the Oswestry Disability Index (ODI) and Short form-36 (SF-36) physical component summary (PCS) scores, and Macnab criteria were evaluated as clinical factors 6 months after treatment. We measured the baseline canal cross-sectional area, ligamentum flavum (LF) area, disc herniation area, dural sac area, fat area, and LF thickness using MRI. A comparative analysis was performed to evaluate the association between radiologic and clinical factors. Additionally, further comparative analyses between the types of surgeries were performed. Among various radiologic factors, the baseline LF thickness (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.25-2.41) was the only major contributing factor to the severity of claudication in the multivariate logistic regression analysis. The types of surgery (decompression alone vs fusion) did not significantly differ in terms of their clinical outcomes, including back and leg VAS, ODI, SF-36 PCS, and satisfaction with the MacNab classification. LF thickness is a major factor contributing to claudication severity.

Safe, Durable, and Sustainable Self-Powered Smart Contact Lenses.

Smart contact lenses have the potential to serve as noninvasive healthcare devices or virtual displays. However, their implementation is limited by the lack of suitable power sources for microelectronic devices. This Article demonstrates smart contact lenses with fully embedded glucose fuel cells that are safe, flexible, and durable against deformations. These fuel cells produced stable power throughout the day or during intermittent use after storage for weeks. When the lenses were exposed to 0.05 mM glucose solution, a steady-state maximum power density of 4.4 µW/cm2 was achieved by optimizing the chemistry and porous structure of the fuel cell components. Additionally, even after bending the lenses in half 100 times, the fuel cell performance was maintained without any mechanical failure. Lastly, when the fuel cells were connected to electroresponsive hydrogel capacitors, we could clearly distinguish between the tear glucose levels under normal and diabetic conditions through the naked eye.

Ion-concentration-polarization-assisted photocatalytic reactor for highly efficient water purification.

Photocatalysis, which utilizes solar energy to electrochemically decompose water pollutants into harmless products, has attracted considerable attention to address serious environmental issues. The photocatalytic effect can be enhanced using an external electric field owing to the inhibition of the recombination of photoexcited electrons and holes. However, the typical linear potential bias that induces a small potential drop across a thin photocatalyst film exhibits a limited photocatalytic reaction. Herein, we propose an ion-concentration-polarization-assisted photocatalytic reactor that generates a nonlinear electric field across the microchannel of this system, which enables an 85.5% increase in the reaction rate compared to that achieved using a linear potential, and a high reaction rate constant up to 12.7 min-1 is achieved. The nonlinear electric field induced by concentration polarization, the nanofluidic electrokinetic phenomenon, results in a considerably increased potential drop across the photocatalyst layer such that the recombination of photoexcited electrons and holes may be efficiently prevented. The facilitated photocatalytic reaction is verified with the plastic film degradation. This proposed enhancing mechanism shows a novel application of nanofluidics for improving the photocatalytic effect, and the potential to be a new class of platform for a photocatalytic reactor owing to its simple configuration and fabrication procedures.

Asymmetric Nanochannel Network-Based Bipolar Ionic Diode for Enhanced Heavy Metal Ion Detection.

A higher rectification degree in ionic diodes is required to achieve better performance in applications. Nonetheless, the active geometrical change that is critical for inducing electrical potential asymmetry is difficult to realize in typical ionic diodes because of the intrinsic limitation of the fabrication method. Here, we propose a nanochannel-network-based bipolar diode with a high rectification degree of ∼1600─the highest value realized until now, to the best of our knowledge. Such a high rectification is obtained based on the synergetic effect of the bipolar surface charge and the optimization of the microchannel through experimental studies and multiphysics numerical simulations. It induces ion concentrations at the heterogeneous junction based on the accumulation effect under the forward potential bias. In particular, this proposed molecular concentration occurs in the ohmic region without vortex and instability that is inevitable at the conventional nano-electrokinetic concentration. Combining this accumulation with the horizontally aligned configuration of the nanochannel network membrane (NCNM), a highly sensitive and quantitative mercury ion (Hg2+) sensor based on a fluorescent signal is fabricated that allows direct measurement using a general fluorescent microscope. The detection limit of Hg2+ is 10 pM, which is ∼10 times lower than the best detection limit realized so far (∼100 pM) in fluorescent dye-based detection. This demonstrates the potential of asymmetric NCNM for high-performance ion transport in applications such as energy conversion, based on its design and material flexibility.

Identification of optimal surgical plan for treatment of extraocular muscle damage in thyroid eye disease patients based on computational biomechanics.

This study replicated the behavior of intraorbital tissue in patients with thyroid eye disease (TED) based on finite element analysis for general orbital decompression risk evaluation in thyroid eye disease patients. The orbit and intraorbital tissues of thyroid eye disease patients who underwent orbital decompression were modeled as finite element models. The stress was examined at specific locations of the removed orbital wall of a thyroid eye disease patient with undergone orbital decompression, and its variation was analyzed as a function of the shape and dimension (to be removed). As a result, in orbital decompression surgery which removes the orbital wall in a rectangular shape, the stress at the orbital wall decreased as the width and depth of the removed orbital wall increased. In addition, in the case of orbital decompression, it can be seen that the chamfered model compared to the non-chamfered model (a form of general orbital decompression) have the stress reduction rate from 11.08% to 97.88%. It is inferred that if orbital decompression surgery considering the chamfered model is performed on an actual thyroid eye disease patient, it is expected that the damage to the extraocular muscle caused by the removed orbital wall will be reduced.

Establishment of a prediction tool for ocular trauma patients with machine learning algorithm.

AIM: To predict final visual acuity and analyze significant factors influencing open globe injury prognosis. METHODS: Prediction models were built using a supervised classification algorithm from Microsoft Azure Machine Learning Studio. The best algorithm was selected to analyze the predicted final visual acuity. We retrospectively reviewed the data of 171 patients with open globe injury who visited the Pusan National University Hospital between January 2010 and July 2020. We then applied cross-validation, the permutation feature importance method, and the synthetic minority over-sampling technique to enhance tool performance. RESULTS: The two-class boosted decision tree model showed the best predictive performance. The accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were 0.925, 0.962, 0.833, 0.893, and 0.971, respectively. To increase the efficiency and efficacy of the prognostic tool, the top 14 features were finally selected using the permutation feature importance method: (listed in the order of importance) retinal detachment, location of laceration, initial visual acuity, iris damage, surgeon, past history, size of the scleral laceration, vitreous hemorrhage, trauma characteristics, age, corneal injury, primary diagnosis, wound location, and lid laceration. CONCLUSION: Here we devise a highly accurate model to predict the final visual acuity of patients with open globe injury. This tool is useful and easily accessible to doctors and patients, reducing the socioeconomic burden. With further multicenter verification using larger datasets and external validation, we expect this model to become useful worldwide.

Combined Effects of Zeta-potential and Temperature of Nanopores on Diffusioosmotic Ion Transport.

Diffusioosmosis (DO) results from ion transport near charged surfaces in the presence of electrolyte gradients and is critical in nanofluidic systems. However, DO has not yet been comprehensively studied because nanofabrication materials have limitations of low throughput and difficult quantification. Herein, we describe a self-assembled particle membrane (SAPM)-integrated microfluidic platform that can modulate the material properties (e.g., zeta-potential) and transport flux of nanopores. We quantify the effect of the zeta-potential on DO by measuring the electrical signals across three different nanopores/nanochannels of the SAPM. We then empirically quantify the effects of the temperature and ionic strength of the electrolytes on DO and reveal a nonlinear relationship with DO-driven ion transport; the ionic strengths govern the DO- or diffusion-effective ion transport phenomena. Finally, we demonstrate DO-driven electric power generation with enhanced performance as a potential application under optimized experimental conditions.