Use of cortical hemodynamic responses in digital therapeutics for upper limb rehabilitation in patients with stroke.

BACKGROUND: Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. METHODS: This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl-Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. RESULTS: The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. CONCLUSIONS: The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Toward maximum energy density enabled by anode-free lithium metal batteries: Recent progress and perspective.

Owing to the emergenceof energy storage and electric vehicles, the desire for safe high-energy-density energy storage devices has increased research interest in anode-free lithium metal batteries (AFLMBs). Unlike general lithium metal batteries (LMBs), in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost-effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency (CE), poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilizing Li metal anodes for AFLMBs. In this review, the importance and challenges of AFLMBs are highlighted. Then, diverse strategies, such as current collectors modification, advanced electrolytes, cathode engineering, and operation protocols are thoroughly reviewed. Finally, a future perspective on the strategy is provided for insight into the basis of future research. It is hoped that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.

Frequency pushing enhanced by an exceptional point in an atom-cavity coupled system.

We observed the frequency pushing of the cavity resonance as a result of the coupling of the cavity field with the ground state 138Ba in a high-Q cavity. A weak probe laser propagated along the axis of a Fabry-Pérot cavity while ground-state barium atoms traversed the cavity mode perpendicularly. By operating the atom-cavity composite in the vicinity of an exceptional point, we could observe a greatly enhanced frequency shift of the cavity transmission peak, which was pushed away from the atomic resonance, resulting in up to 41 ± 7 kHz frequency shift per atom from the empty cavity resonance. We analyzed our results by using the Maxwell-Schrödinger equation and obtained good agreement with the measurements.

Effect of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Background: Arthroscopic rotator cuff repair (RCR) is a common orthopaedic procedure, but it has a high rate of retears that can negatively affect the functional outcomes. Bone marrow stimulation (BMS) has been suggested as an additional treatment to improve the outcomes of RCR. Purpose: To compare the effectiveness of the BMS procedure during RCR with conventional RCR. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic literature search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, and Scopus, on March 1, 2023, for studies comparing postoperative retear rates and functional outcomes between patients who underwent primary arthroscopic RCR with and without the BMS procedure. Only level 1 and 2 randomized controlled trials with a minimum 12-month follow-up were included. The primary outcomes were retear rates and functional outcomes as measured by the Constant; American Shoulder and Elbow Surgeons (ASES); and University of California, Los Angeles (UCLA) scores and by postoperative range of motion. Subgroup analyses were performed based on repair technique (single-row repair vs double-row or suture-bridge repair). The standardized mean difference (SMD) and odds ratio (OR) were utilized to synthesize continuous and dichotomous outcomes, respectively. Homogeneity was evaluated using the chi-square test and I2 statistic. Results: The literature search yielded 661 articles, of which 6 studies (522 patients; 261 with BMS, 261 without BMS) met the eligibility criteria. The combined analysis showed no significant decrease in retear rates with the utilization of the BMS procedure during RCR (OR, 0.60; 95% CI, 0.35 to 1.03; P = .07; I2 = 24%). There was no significant intergroup difference in functional outcomes (Constant score: SMD, 0.13; 95% CI, -0.04 to 0.31; P = .13; I2 = 0%; ASES score: SMD, 0.04; 95% CI, -0.20 to 0.28; P = .73; I2 = 0%; UCLA score: SMD, -0.13; 95% CI, -0.50 to 0.23; P = .47; I2 = 0%). Subgroup analyses revealed no significant differences in postoperative retear risk or total Constant score according to the repair technique. Conclusion: Based on the available evidence, this systematic review did not find a significant benefit of the BMS procedure at the footprint during arthroscopic RCR compared with conventional RCR in terms of retear rates and functional outcomes at short-term follow-up.

Anisotropic lens-shaped mesoporous carbon from interfacially perpendicular self-assembly for potassium-ion batteries.

Anisotropic lens-shaped nitrogen-doped carbon (Lens-NMC) with unidirectionally aligned mesopores was achieved via perpendicular block copolymer self-assembly at the polymer interface. Lens-NMC is applied as a potassium-ion battery anode material as a next-generation battery system.

Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family.

Structural and mechanistic studies on human odorant receptors (ORs), key in olfactory signaling, are challenging because of their low surface expression in heterologous cells. The recent structure of OR51E2 bound to propionate provided molecular insight into odorant recognition, but the lack of an inactive OR structure limited understanding of the activation mechanism of ORs upon odorant binding. Here, we determined the cryo-electron microscopy structures of consensus OR52 (OR52cs), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52cs reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52cs demonstrates the inward and outward movements of the extracellular and intracellular segments of TM6, respectively. These results, combined with molecular dynamics simulations and signaling assays, shed light on the molecular mechanisms of odorant binding and activation of the OR52 family.

Changes in Thermal Stress in Korea Using Climate-Based Indicators: Present-Day and Future Projections from 1 km High Resolution Scenarios.

Among the various thermal stress indices, apparent temperature (AT) is closely related to public health indicators, and consequently is widely used by weather agencies around the world. Therefore, in this paper we estimate the changes in AT and contributing components in Korea as a whole and in five major cities (Seoul, Gwanju, Daegu, Daejeon, and Busan) using national standard climate scenarios based on the coupled model inter-comparison project (CMIP6). In the present day, high AT occurs in major cities due to high temperature (TAS) and relative humidity (RH). Our findings reveal that even when TAS is relatively low, large AT occurs with higher humidity. Notably, in future warmer climate conditions, high AT may first appear in the five major cities and then extend to the surrounding areas. An increase in TAS and RH during the pre-hot season (March to June) may lead to earlier occurrence of thermal risks in future warmer climate conditions and more frequent occurrence of high thermal stress events. Our study can serve as a reference for future information on thermal risk changes in Korea. Considering those who have not adapted to high temperature environments, our findings imply that thermal risks will become more serious and that heat adaptation strategies will be needed during the pre-hot season under future warmer climate conditions.

Limited output transcranial electrical stimulation 2023 (LOTES-2023): Updates on engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

The objective and scope of this Limited Output Transcranial Electrical Stimulation 2023 (LOTES-2023) guidance is to update the previous LOTES-2017 guidance. These documents should therefore be considered together. The LOTES provides a clearly articulated and transparent framework for the design of devices providing limited output (specified low-intensity range) transcranial electrical stimulation for a variety of intended uses. These guidelines can inform trial design and regulatory decisions, but most directly inform manufacturer activities - and hence were presented in LOTES-2017 as "Voluntary industry standard for compliance controlled limited output tES devices". In LOTES-2023 we emphasize that these standards are largely aligned across international standards and national regulations (including those in USA, EU, and South Korea), and so might be better understood as "Industry standards for compliance controlled limited output tES devices". LOTES-2023 is therefore updated to reflect a consensus among emerging international standards, as well as best available scientific evidence. "Warnings" and "Precautions" are updated to align with current biomedical evidence and applications. LOTES standards applied to a constrained device dose range, but within this dose range and for different use-cases, manufacturers are responsible to conduct device-specific risk management.

Impact of Chronic Obstructive Pulmonary Disease on Outcomes After Total Joint Arthroplasty: A Meta-analysis and Systematic Review.

Background: Comorbid chronic obstructive pulmonary disease (COPD) is increasingly common and may have an adverse impact on outcomes in patients undergoing total joint arthroplasty (TJA) of lower extremity. The purpose of this meta-analysis is to compare the postoperative complications between COPD and non-COPD patients undergoing primary TJA including total hip and knee arthroplasty. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies published before December 2021. Postoperative outcomes were compared between patients with COPD versus those without COPD as controls. The outcomes were mortality, re-admission, pulmonary, cardiac, renal, thromboembolic complications, surgical site infection (SSI), periprosthetic joint infection (PJI), and sepsis. Results: A total of 1,002,779 patients from nine studies were finally included in this meta-analysis. Patients with COPD had an increased risk of mortality (OR [odds ratio] = 1.69, 95% confidence interval [CI] 1.42-2.02), re-admission (OR = 1.54, 95% CI 1.38-1.71), pulmonary complications (OR = 2.73, 95% CI 2.26-3.30), cardiac complications (OR = 1.40, 95% CI 1.15-1.69), thromboembolic complications (OR = 1.21, 95% CI 1.15-1.28), renal complications (OR = 1.50, 95% CI 1.14-1.26), SSI (OR = 1.23, 95% CI 1.18-1.30), PJI (OR = 1.26, 95% CI 1.15-1.38), and sepsis (OR = 1.36, 95% CI 1.22-1.52). Conclusion: Patients with comorbid COPD showed an increased risk of mortality and postoperative complications following TJA compared with patients without COPD. Therefore, orthopedic surgeons can use the study to adequately educate these potential complications when obtaining informed consent. Furthermore, preoperative evaluation and medical optimization are crucial to minimizing postoperative complications from arising in this difficult-to-treat population. Level of evidence: Level III. Registration: None. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00794-2.

Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling.

Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors (Y1R and Y2R, respectively) activate GI signaling, but their physiological responses to food intake are different. In addition, deletion of the two N-terminal amino acids of peptide YY (PYY(3-36)), the endogenous form found in circulation, can stimulate Y2R but not Y1R, suggesting that Y1R and Y2R may have distinct ligand-binding modes. Here, we report the cryo-electron microscopy structures of the PYY(3-36)‒Y2R‒Gi and NPY‒Y2R‒Gi complexes. Using cell-based assays, molecular dynamics simulations, and structural analysis, we revealed the molecular basis of the exclusive binding of PYY(3-36) to Y2R. Furthermore, we demonstrated that Y2R favors G protein signaling over ß-arrestin signaling upon activation, whereas Y1R does not show a preference between these two pathways.

Alterations in cognitive function and blood biomarkers following transcranial direct current stimulation in patients with amyloid positron emission tomography-positive Alzheimer's disease: a preliminary study.

Introduction: Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive cognitive decline. To address this, we conducted a randomized, double-blinded, sham-controlled study to investigate the therapeutic potential of transcranial direct current stimulation (tDCS) on patients with amyloid positron emission tomography (PET)- positive AD. Methods: Participants already undergoing pharmacological treatment and testing positive for amyloid PET were divided into Active-tDCS (n = 8) and Sham-tDCS (n = 8) groups. For 12 weeks, participants or their caregivers administered daily bi-frontal tDCS (YMS-201B+, Ybrain Inc., Seongnam, Korea) at home (2 mA, 30 min). Pre- and post-intervention assessments included neuropsychological tests and blood sample measurements for oligomerized beta-amyloid. Results: The Active-tDCS group demonstrated significant improvements in cognitive domains such as language abilities, verbal memory, and attention span and in frontal lobe functions compared to the Sham-tDCS group. Furthermore, the Active-tDCS group showed a marked reduction in post-intervention plasma Aß oligomerization tendency level, suggesting changes in pivotal AD-associated biomarkers. Discussion: Our results emphasize the potential therapeutic benefits of tDCS for mild AD patients with amyloid PET positivity and stress the urgency for broader research, considering the global challenges of dementia and the need to pursue innovative therapeutic strategies.

Observation of a half-illuminated mode in an open Penrose cavity.

The illumination problem in mathematics questions the existence of a bounded region in which light rays from a point light source do not illuminate the whole region. Since Penrose disproved the illumination problem with elliptical reflective boundaries, the interest has mostly remained in ray optics mainly because there can be no completely dark region for light waves due to diffraction. Here, in a two-dimensional Penrose cavity with elliptical boundaries, we report experimental observation of a symmetry-broken mode in the long-wavelength regime with the half of the cavity region with reflection symmetry almost unilluminated in the steady state. The half-illuminated mode (HIM) was observed in an acoustic cavity by using the schlieren method. The HIM originated from the coherent superposition of near-degenerate modes, among which two scarred modes with opposite parities played a major role. The illuminated part of the HIM could be even flipped by choosing different coefficients in the coherent superposition of the participating modes. The HIM of the Penrose cavity provides new perspective to the illumination problem in an open system.

Task-Related Hemodynamic Changes Induced by High-Definition Transcranial Direct Current Stimulation in Chronic Stroke Patients: An Uncontrolled Pilot fNIRS Study.

High-definition transcranial direct current stimulation (HD-tDCS) has recently been proposed as a tDCS approach that can be used on a specific cortical region without causing undesirable stimulation effects. In this uncontrolled pilot study, the cortical hemodynamic changes caused by HD-tDCS applied over the ipsilesional motor cortical area were investigated in 26 stroke patients. HD-tDCS using one anodal and four cathodal electrodes at 1 mA was administered for 20 min to C3 or C4 in four daily sessions. Cortical activation was measured as changes in oxyhemoglobin (oxyHb) concentration, as found using a functional near-infrared spectroscopy (fNIRS) system during the finger tapping task (FTT) with the affected hand before and after HD-tDCS. Motor-evoked potential and upper extremity functions were also measured before (T0) and after the intervention (T1). A group statistical parametric mapping analysis showed that the oxyHb concentration increased during the FTT in both the affected and unaffected hemispheres before HD-tDCS. After HD-tDCS, the oxyHb concentration increased only in the affected hemisphere. In a time series analysis, the mean and integral oxyHb concentration during the FTT showed a noticeable decrease in the channel closest to the hand motor hotspot (hMHS) in the affected hemisphere after HD-tDCS compared with before HD-tDCS, in accordance with an improvement in the function of the affected upper extremity. These results suggest that HD-tDCS might be helpful to rebalance interhemispheric cortical activity and to reduce the hemodynamic burden on the affected hemisphere during hand motor tasks. Noticeable changes in the area adjacent to the affected hMHS may imply that personalized HD-tDCS electrode placement is needed to match each patient's individual hMHS location.

Multichannel Transcranial Direct Current Stimulation Combined With Treadmill Gait Training in Patients With Parkinson's Disease: A Pilot Study.

Background: Gait problems are critical impairments in Parkinson's disease (PD) and are related to increased risk of fall and negatively impact activities of daily life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modify the cortical excitability of gait-related brain regions. In this study, we investigated whether multichannel tDCS with simultaneous treadmill gait training could improve gait in PD. Methods: Twenty-four patients with PD were assigned randomly to a real or sham tDCS group. Before intervention, one patient of the real tDCS group was dropped out, leaving 23 patients to be analyzed in this study. Each patient underwent 30 min of treadmill gait training for 10 sessions over four consecutive weeks. Multichannel 4x1 tDCS was applied using five 6-cm-diameter round electrodes. One anode was placed on the CZ, and four cathodes were positioned symmetrically over the FZ, C5, C6, and PZ. Anodal tDCS (2mA) and sham tDCS were delivered for 20 min. The secondary outcomes were gait performance, as measured by the timed up and go test (TUG) and freezing of gait questionnaire (FOG-Q), and balance was assessed using the dynamic gait index (DGI), Berg balance scale (BBS), and functional reach test (FRT). Motor and non-motor performance of patients with PD were assessed using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Participants were assessed before the intervention, immediately after the intervention, and 4 weeks after completion of the intervention. Results: The real tDCS group showed a significant improvement in the 10-m walk test, but the sham group did not. Among the secondary outcome measures, MDS-UPDRS part II, TUG, and BBS were improved only in the real tDCS group. Particularly, MDS-UPDRS part II showed a significant group*time interaction effect, indicating that real tDCS demonstrated a better effect on the activities of daily living patients with PD. Conclusions: The results of this pilot study suggest that multichannel tDCS applied on the leg motor cortex during treadmill gait training is a safe and effective means to improve gait velocity in patients with PD. Additional rigorous, large-sample, multicenter, randomized controlled trials are needed to confirm the effect of tDCS as a therapeutic adjunct for gait rehabilitation of patients with PD.

Whole Brain Hemodynamic Response Based on Synchrony Analysis of Brain Signals for Effective Application of HD-tDCS in Stroke Patients: An fNIRS Study.

In this study, the effective application of high-definition transcranial direct current stimulation (HD-tDCS) based on the whole brain hemodynamic response in stroke patients was investigated using functional near-infrared spectroscopy (fNIRS). The intrahemispheric and interhemispheric synchronization and cortical activity based on the time during 1 mA HD-tDCS were examined in 26 chronic cerebrovascular disease patients. At the beginning of HD-tDCS, the synchronization and brain activity in the whole brain increased rapidly and decreased after 5 min. In the middle of tDCS, the synchronization began to increase again, and strong synchronic connections were formed around the desired stimulation area. After tDCS, strong cortical activation was observed in the stimulation area, indicating that the baseline of the oxyhemoglobin (HbO) signal increased in the desired stimulation area. Therefore, the results of this study indicate that HD-tDCS can be applied efficiently to enhance the effect of tDCS. This stimulation method with tDCS can be explored clinically for more neurorehabilitation of patients with degenerative brain diseases.

Structural basis of neuropeptide Y signaling through Y1 receptor.

Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1 protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.

Multimodal Imaging Biomarker-Based Model Using Stratification Strategies for Predicting Upper Extremity Motor Recovery in Severe Stroke Patients.

Background. Various prognostic biomarkers for upper extremity (UE) motor recovery after stroke have been reported. However, most have relatively low predictive accuracy in severe stroke patients.Objective. This study suggests an imaging biomarker-based model for effectively predicting UE recovery in severe stroke patients.Methods. Of 104 ischemic stroke patients screened, 42 with severe motor impairment were included. All patients underwent structural, diffusion, and functional magnetic resonance imaging at 2 weeks and underwent motor function assessments at 2 weeks and 3 months after stroke onset. According to motor function recovery at 3 months, patients were divided into good and poor subgroups. The value of multimodal imaging biomarkers of lesion load, lesion volume, white matter integrity, and cortical functional connectivity for motor recovery prediction was investigated in each subgroup.Results. Imaging biomarkers varied depending on recovery pattern. The integrity of the cerebellar tract (P = .005, R2 = .432) was the primary biomarker in the good recovery group. In contrast, the sensory-related corpus callosum tract (P = .026, R2 = .332) and sensory-related functional connectivity (P = .001, R2 = .531) were primary biomarkers in the poor recovery group. A prediction model was proposed by applying each biomarker in the subgroup to patients with different motor evoked potential responses (P < .001, R2 = .853, root mean square error = 5.28).Conclusions. Our results suggest an optimized imaging biomarker model for predicting UE motor recovery after stroke. This model can contribute to individualized management of severe stroke in a clinical setting.