Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.

Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.

Reduced physiological extrusion of the medial meniscus in axial load-bearing condition in anterior cruciate ligament deficiency.

PURPOSE: In this study, ultrasonography was used to measure medial meniscus (MM) extrusion under weight-bearing and nonweight-bearing conditions in both anterior cruciate ligament (ACL)-deficient and ACL-intact knee groups. This study aimed to determine the possible differences between these groups with an eventual impact on meniscal tears in ACL-deficient knees. METHODS: A total of 107 patients who underwent ACL reconstructive surgery between June 2022 and April 2023 were enroled. After applying exclusion criteria, 37 patients met the conditions for inclusion in the study and formed the ACL deficiency group (Group D). Of the 141 patients presenting to an outpatient clinic who agreed to have ultrasonography conducted on their nondiscomforting contralateral knee, 37 patients matched for age, sex, hip-knee-ankle angle and body mass index with Group D patients were selected for the ACL intact group (Group I). Ultrasonography was used to measure MM extrusion in weight-bearing and nonweight-bearing conditions for all participants. RESULTS: Seventy-four patients were included in the study (n = 37 per group). The supine position showed an MM extrusion of 1.2 ± 0.7 mm in Group I and 1.2 ± 0.7 mm in Group D (not significant). In the standing position, MM extrusion measured 2.0 ± 0.6 mm in Group I and 1.3 ± 0.8 mm in Group D. The difference in extrusion (Δextrusion) between the two positions was 0.8 ± 0.6 in Group I and 0.1 ± 0.2 in Group D, with statistical significance (p < 0.01). A consistent reduction in MM extrusion during weight-bearing was observed in patients with ACL deficiency, irrespective of the duration of ACL deficiency, age, sex and BMI. CONCLUSION: ACL deficiency did not significantly impact MM extrusion during nonweight-bearing conditions; however, less MM extrusion was observed in response to axial loading conditions. These findings indicate altered MM biomechanics due to increased anterior-posterior meniscal motion and rotational instability after ACL injury. LEVEL OF EVIDENCE: Level III.

Automating the High-Throughput Screening of Protein-Based Optical Indicators and Actuators.

Over the last 25 years, protein engineers have developed an impressive collection of optical tools to interface with biological systems: indicators to eavesdrop on cellular activity and actuators to poke and prod native processes. To reach the performance level required for their downstream applications, protein-based tools are usually sculpted by iterative rounds of mutagenesis. In each round, libraries of variants are made and evaluated, and the most promising hits are then retrieved, sequenced, and further characterized. Early efforts to engineer protein-based optical tools were largely manual, suffering from low throughput, human error, and tedium. Here, we describe approaches to automating the screening of libraries generated as colonies on agar, multiwell plates, and pooled populations of single-cell variants. We also briefly discuss emerging approaches for screening, including cell-free systems and machine learning.

Electrochemical and electrophysiological considerations for clinical high channel count neural interfaces.

Electrophysiological recording and stimulation are the gold standard for functional mapping during surgical and therapeutic interventions as well as capturing cellular activity in the intact human brain. A critical component probing human brain activity is the interface material at the electrode contact that electrochemically transduces brain signals to and from free charge carriers in the measurement system. Here, we summarize state-of-the-art electrode array systems in the context of translation for use in recording and stimulating human brain activity. We leverage parametric studies with multiple electrode materials to shed light on the varied levels of suitability to enable high signal-to-noise electrophysiological recordings as well as safe electrophysiological stimulation delivery. We discuss the effects of electrode scaling for recording and stimulation in pursuit of high spatial resolution, channel count electrode interfaces, delineating the electrode-tissue circuit components that dictate the electrode performance. Finally, we summarize recent efforts in the connectorization and packaging for high channel count electrode arrays and provide a brief account of efforts toward wireless neuronal monitoring systems.

Latarjet procedure for failed Bankart repair provides better stability and return to sports, but worse postoperative pain and external rotation limitations with more complications, compared to revision Bankart repair: a systematic review and meta-analysis.

PURPOSE: This study aimed to compare the clinical results of revision Bankart repair versus the Latarjet procedure for failed Bankart repair. METHODS: A literature search was performed in databases, such as Pubmed, Embase, and Scopus Library. The studies were appraised using the Methodological Index for Non-randomized Studies tool. Studies for failed Bankart repair with revision Bankart repair or Latarjet procedure were included. The pain VAS, ROWE score, rate of return to sports and preinjury level of sports, recurrent instability, range of motion, and complications were compared. Additionally, the pain VAS, ROWE score, forward flexion, and external rotation at side were subjected to a meta-analysis. RESULTS: Twenty-four articles were included in the systematic review. The functional outcomes in terms of the ROWE score, recurrent instability, return to sports, and the preinjury level of sports was better in the Latarjet procedure group than those in the revision Bankart repair group (ROWE score, 91 vs. 86.7; recurrent instability rate, 3.5% vs. 14.4%; return to sports rate, 100% vs. 87.9%; return to preinjury level of sports rate, 89.9% vs. 74.9%; all P < 0.001). However, the results of postoperative pain and the postoperative limitation of external rotation at side were worse in the Latarjet procedure group than those in the revision Bankart repair group (pain VAS, 1.4 vs. 0.8; postoperative external rotation at side, 38° vs. 60°; all P < 0.001). In addition, the majority of the complications occurred in the Latarjet procedure group. In the meta-analysis, the postoperative ROWE score was significantly higher in the Latarjet procedure group than that in the revision Bankart group (revision Bankart repair: 95% CI 88.9-80.9, I2 = 65.70; Latarjet procedure: 95% CI 95.8-88.1, I2 = 93.37; P = 0.014). However, the pain VAS, forward flexion, and external rotation at side did not reach the significant level in the meta-analysis. CONCLUSION: Compared with revision Bankart repair, the Latarjet procedure for failed Bankart repair showed better ROWE scores, stability, and return to sports or preinjury level of sports; however, the postoperative pain and the limitation of external rotation at side were worse with more complications. IRB NO: KUMC 2022-01-024. LEVEL OF EVIDENCE: Level IV.

Single-incision bone bridge lateral meniscus allograft transplantation: preserving neurovascular safety with promising results for posterior horn distortion and graft maturation.

PURPOSE: This study aimed to investigate the graft maturation and safety of single-incision bone bridge lateral meniscus allograft transplantation (LMAT). METHODS: This study involved 35 patients who underwent LMAT between 2019 and 2020. All patients completed at least 2 years of follow-up (median 34 months; range 24-43) and underwent preoperative magnetic resonance imaging (MRI) to assess the trajectory safety of the leading suture passer and all-inside suture instrument (Fast-Fix). Graft status was evaluated according to the Stoller classification. RESULTS: Based on preoperative MRI measurements, the expected trajectory of the leading suture passer did not transect the common peroneal nerve (CPN), with the closest distance between the expected trajectory and CPN being 1.4 mm and the average distance being 6.8 ± 3.2 mm. The average distance from the lateral meniscal posterior horn (LMPH) to the popliteal neurovascular bundle (PNVB) was 7.4 ± 2.6 mm and the nearest was 4.8 mm. The expected trajectory of the all-inside suturing instrument did not transect the PNVB when the distance was at least 12 mm, from the most lateral margin of the posterior cruciate ligament (PCL). Grade 3 signal intensity in the posterior third of the allograft on MRI was observed in 6 of 35 (17.1%) patients. Amongst the grade 3 signal intensities in the posterior one-third of the allografts, 3 of the 35 (8.5%) LMATs had a distorted contour. CONCLUSION: The single-incision bone bridge LMAT technique introduced in this study is a convenient approach that preserves neurovascular safety and provides good results for the distortion of the posterior horn of the allograft and graft maturation. The safety zone for the penetrating devices during the procedure extended from 12 mm laterally to the most lateral margin of the PCL to the medial margin of the popliteal hiatus. LEVEL OF EVIDENCE: IV.

Superior capsular reconstruction using hybrid graft for irreparable massive rotator cuff tear.

PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopic superior capsular reconstruction (SCR) using hybrid grafts composed of tensor fascia lata autografts and human dermal allografts. METHODS: This study included 30 patients with chronic irreparable posterosuperior rotator cuff tears (RCTs) who underwent arthroscopic SCR using a hybrid graft composed of tensor fascia lata autograft and human dermal allograft. Clinical outcomes were evaluated using the pain visual analogue scale score, shoulder range of motion, American Shoulder and Elbow Surgeons score, constant score, University of California-Los Angeles score, and simple shoulder test score preoperatively and at least 2 years after surgery. Radiographic analysis included the Hamada classification grade, acromiohumeral distance (AHD), and graft integrity at 2 years after surgery. RESULTS: All patients exhibited significant clinical improvement in all functional outcome measurements, except external rotation (all P < 0.05). The number of patients who exhibited pseudoparalysis decreased from 7 (23.3%) to 2 (6.7%) postoperatively. Complications were not observed. Radiologically, the mean postoperative AHD increased significantly from 6.9 ± 1.6 cm to 8.8 ± 2.1 cm at 2 years postoperatively (P < 0.001). Twenty five out of the 30 (83.3%) patients showed successful graft healing, and all healing failures occurred on the humeral side. The differences between the healed-graft and failed-graft groups were significantly lower graft thickness (P = 0.001) and smaller AHD (P < 0.001) in the failed-graft group. Every functional outcome scores were not statistically different between healed-graft and failed-graft groups. CONCLUSIONS: An arthroscopic SCR technique using a hybrid graft consisting of a tensor fascia lata autograft and human dermal allograft showed satisfactory clinical outcomes in patients with irreparable RCTs. LEVEL OF EVIDENCE: IV.

Feature Attribution Analysis to Quantify the Impact of Oceanographic and Maneuverability Factors on Vessel Shaft Power Using Explainable Tree-Based Model.

A vessel sails above the ocean against sea resistance, such as waves, wind, and currents on the ocean surface. Concerning the energy efficiency issue in the marine ecosystem, assigning the right magnitude of shaft power to the propeller system that is needed to move the ship during its operations can be a contributive study. To provide both desired maneuverability and economic factors related to the vessel's functionality, this research studied the shaft power utilization of a factual vessel operational data of a general cargo ship recorded during 16 months of voyage. A machine learning-based prediction model that is developed using Random Forest Regressor achieved a 0.95 coefficient of determination considering the oceanographic factors and additional maneuver settings from the noon report data as the model's predictors. To better understand the learning process of the prediction model, this study specifically implemented the SHapley Additive exPlanations (SHAP) method to disclose the contribution of each predictor to the prediction results. The individualized attributions of each important feature affecting the prediction results are presented.

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

Antimicrobial properties of Limosilactobacillus reuteri strains for control of Escherichia coli and Salmonella strains, diarrhoea cause in weaning pigs.

This study aimed to use lactic acid bacteria isolated from piglet faeces to develop probiotics, allowing for the effective control of Escherichia coli and Salmonella. Lactic acid bacteria were isolated from the faeces of suckling piglets and identified by 16S rRNA sequencing, then examined for haemolysis; gelatinase activity; and resistance to acid, bile, and pancreatin. The antimicrobial activity of selected lactic acid bacteria isolates was examined for 8 E. coli and 7 Salmonella strains. One-hundred and sixty-four lactic acid bacteria isolates were identified from 118 piglet faecal samples, and 13 lactic acid bacteria isolates were selected from analyses of haemolysis; gelatinase activity; and resistance to acid, bile, and pancreatin. Of the selected 13 lactic acid bacteria isolates, Limosilactobacillus reuteri PF20-3 and PF30-3 strains had the highest antibacterial activity against E. coli and Salmonella.

Retrospective study using biosensor data of a milking Holstein cow with jejunal haemorrhage syndrome.

Jejunal haemorrhage syndrome (JHS) is a sporadic and fatal enterotoxaemic disease in dairy cows associated with acute development and poor prognosis despite treatment. A 5-year-old Holstein cow with no reported pregnancy, three calving numbers, and 303 days in milk presented with hypothermia, discomfort, and inappetence. Anaemia, dehydration, faeces with blood clots, and absence of rumen and bowel movements were observed. We identified the presence of neutrophilia, hyperglycaemia, hypoproteinaemia, azotaemia, hyperlactatemia, hypocalcaemia, hypermagnesemia, hypokalaemia, and hypochloraemia through blood analyses. Necropsy and histopathologic examination revealed a dilated bluish-purple jejunum, blood clots within the jejunum, neutrophil infiltration into the submucosa of the jejunum, and vascular necrosis. Retrospective examination revealed extraordinary patterns of rumination time, activity, rumen mobility, and rumen temperature using biosensors and decreased milk yield. The abnormalities in the affected cow were detected before recognition by farm workers. To the best of our knowledge, this is the first report to examine data from biosensors in a cow with JHS. Our findings suggest that using biometric data may help understand the development of JHS.

Ultra-Sharp Nanowire Arrays Natively Permeate, Record, and Stimulate Intracellular Activity in Neuronal and Cardiac Networks.

We report innovative scalable, vertical, ultra-sharp nanowire arrays that are individually addressable to enable long-term, native recordings of intracellular potentials. Stable amplitudes of intracellular potentials from 3D tissue-like networks of neurons and cardiomyocytes are obtained. Individual electrical addressability is necessary for high-fidelity intracellular electrophysiological recordings. This study paves the way toward predictive, high-throughput, and low-cost electrophysiological drug screening platforms.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Explainable Anomaly Detection Framework for Maritime Main Engine Sensor Data.

In this study, we proposed a data-driven approach to the condition monitoring of the marine engine. Although several unsupervised methods in the maritime industry have existed, the common limitation was the interpretation of the anomaly; they do not explain why the model classifies specific data instances as an anomaly. This study combines explainable AI techniques with anomaly detection algorithm to overcome the limitation above. As an explainable AI method, this study adopts Shapley Additive exPlanations (SHAP), which is theoretically solid and compatible with any kind of machine learning algorithm. SHAP enables us to measure the marginal contribution of each sensor variable to an anomaly. Thus, one can easily specify which sensor is responsible for the specific anomaly. To illustrate our framework, the actual sensor stream obtained from the cargo vessel collected over 10 months was analyzed. In this analysis, we performed hierarchical clustering analysis with transformed SHAP values to interpret and group common anomaly patterns. We showed that anomaly interpretation and segmentation using SHAP value provides more useful interpretation compared to the case without using SHAP value.

Magnetothermia-Induced Catalytic Hollow Nanoreactor for Bioorthogonal Organic Synthesis in Living Cells.

Nanoreactors, in which the reactions are remotely controlled by magnetic fields, are potentially valuable in bioorthogonal chemistry for future applications. Here, we develop a silica-confined magnetothermia-induced nanoreactor (MAG-NER) by selectively growing Pd nanocrystals on a preinstalled iron-oxide core inside a hollow silica nanoshell. The growth is achieved by magnetic induction. The interfacial catalytic site is activated by stimulating localized magnetothermia, and nanocompartmentalization is realized by the size-selective porous silica. Therefore, MAG-NER can be conveniently used in complex biomedia and can even be internalized to living cells, realizing an on-demand, high-performance intramolecular carbocyclization reaction by remote operation without compromising the cell viability. This work opens avenues for the design of advanced nanoreactors that complement and augment the existing bioorthogonal chemical tools.

An Ensemble-Based Approach to Anomaly Detection in Marine Engine Sensor Streams for Efficient Condition Monitoring and Analysis.

This study proposes an unsupervised anomaly detection method using sensor streams from the marine engine to detect the anomalous system behavior, which may be a possible sign of system failure. Previous works on marine engine anomaly detection proposed a clustering-based or statistical control chart-based approach that is unstable according to the choice of hyperparameters, or cannot fit well to the high-dimensional dataset. As a remedy to this limitation, this study adopts an ensemble-based approach to anomaly detection. The idea is to train several anomaly detectors with varying hyperparameters in parallel and then combine its result in the anomaly detection phase. Because the anomaly is detected by the combination of different detectors, it is robust to the choice of hyperparameters without loss of accuracy. To demonstrate our methodology, an actual dataset obtained from a 200,000-ton cargo vessel from a Korean shipping company that uses two-stroke diesel engine is analyzed. As a result, anomalies were successfully detected from the high-dimensional and large-scale dataset. After detecting the anomaly, clustering analysis was conducted to the anomalous observation to examine anomaly patterns. By investigating each cluster's feature distribution, several common patterns of abnormal behavior were successfully visualized. Although we analyzed the data from two-stroke diesel engine, our method can be applied to various types of marine engine.

Data-Driven Prediction of Vessel Propulsion Power Using Support Vector Regression with Onboard Measurement and Ocean Data.

The fluctuation of the oil price and the growing requirement to reduce greenhouse gas emissions have forced ship builders and shipping companies to improve the energy efficiency of the vessels. The accurate prediction of the required propulsion power at various operating condition is essential to evaluate the energy-saving potential of a vessel. Currently, a new ship is expected to use the ISO15016 method in estimating added resistance induced by external environmental factors in power prediction. However, since ISO15016 usually assumes static water conditions, it may result in low accuracy when it is applied to various operating conditions. Moreover, it is time consuming to apply the ISO15016 method because it is computationally expensive and requires many input data. To overcome this limitation, we propose a data-driven approach to predict the propulsion power of a vessel. In this study, support vector regression (SVR) is used to learn from big data obtained from onboard measurement and the National Oceanic and Atmospheric Administration (NOAA) database. As a result, we show that our data-driven approach shows superior performance compared to the ISO15016 method if the big data of the solid line are secured.

Metal@SiO2 Core-Shells with Self-Arrested Migrating Core.

Developing easy and customizable strategies for the directional structure modulation of multicomponent nanosystems to influence and optimize their properties are a paramount but challenging task in nanoscience. Here, we demonstrate highly controlled eccentric off-center positioning of metal-core in metal@silica core-shells by utilizing an in situ generated biphasic silica-based intraparticle solid-solid interface. In the synthetic strategy, by including Ca2+-ions in silica-shell and successive oxidative and reductive annealing at high temperature, a unique hairline-biphasic interface is evolved via the heat-induced concentric radial segregation of calcium silicate phase at the interior and normal silica phase at the exterior of core-shell, which can effectively arrest the outwardly migrating metal-core within rubbery calcium silicate phase, affording various eccentric core-shells, where core-positions are flexibly controlled by the annealing time and amounts of initially added Ca2+-ions. In the structure-property correlation study, the strategy allows fine-tuning of dipolar interaction-based blocking temperatures and magnetic anisotropies of different eccentric core-shells as the function of variable off-center distance of magnetic core without changing the overall size of nanoparticles. This work demonstrates the discovery and potential application of biphasic solid-solid media interface in controlling the heat-induced migration of metal nanocrystals and opens the avenues for exploiting the rarely studied high-temperature solid-state nanocrystal conversion chemistry and migratory behavior for directional nanostructure engineering.

Monofacet-Selective Cavitation within Solid-State Silica-Nanoconfinement toward Janus Iron Oxide Nanocube.

Here, a highly selective solid-state nanocrystal conversion strategy is developed toward concave iron oxide (Fe3O4) nanocube with an open-mouthed cavity engraved exclusively on a single face. The strategy is based on a novel heat-induced nanospace-confined domino-type migration of Fe2+ ions from the SiO2-Fe3O4 interface toward the surrounding silica shell and concomitant self-limiting nanoscale phase-transition to the Fe-silicate form. Equipped with the chemically unique cavity, the produced Janus-type concave iron oxide nanocube was further functionalized with controllable density of catalytic Pt-nanocrystals exclusively on concave sites and utilized as a highly diffusive catalytic Janus nanoswimmer for the efficient degradation of pollutant-dyes in water.

Anisotropic vacancy-mediated phonon mode softening in Sm and Gd doped ceria.

Ceria doped with Sm and Gd (SDC and GDC) has been suggested as a promising candidate for the electrolyte used in solid oxide fuel cells (SOFCs), since it has relatively high oxygen ion conductivity at intermediate temperature. There have been many previous experimental and computational studies to investigate the properties, structure, and effect of vacancies, etc. for SDC and GDC. However, in these previous studies, it is commonly assumed that the interaction between oxygen vacancies is negligible and many focus only on the mono-vacancy system. In addition, the possibility of anisotropic vibrational motion of the oxygen ions around vacancies is often neglected. In this paper, using both first-principle density-functional theory and classical molecular dynamics calculations, we investigate the structural and vibrational properties of the optimized SDC and GDC structures, such as bonding analysis, phonon density-of-state and mean-square-displacement of the oxygen ions. Also, we report the direction-dependent vibrations at the specific frequency of the oxygen ions near the vacancies, activation energies, and diffusion coefficients of SDC and GDC which can extend our understanding of diffusion dynamics in doped ceria-based electrolytes for SOFC applications.