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Kyun-Ho Shin, Jae-Joong Kim, Sei-Wook Son, Kyo-Sun Hwang, Seung-Beom Han Department of Orthopaedic Surgery, Anam Hospital, Korea University College of Medicine, Seoul, South KoreaCorrespondence: Seung-Beom HanKorea University College of Medicine, 73 Inchon-Ro, Sungbuk-gu, Seoul 02841, South KoreaTel +82-2-920-5924Fax +82-2-924-2471Email oshan@korea.ac.krPurpose: Postoperative pneumonia is a common and devastating complication of hip fracture surgery in older individuals. This study aimed to determine the relationship between early postoperative hypoalbuminaemia and pneumonia after hip fracture surgery.Patients and Methods: In this retrospective cohort study conducted at one centre, we reviewed the medical records of 1155 consecutive patients (> 60 years) who underwent hip fracture surgery. Multivariate logistic regression analysis was performed to identify the independent risk factors for postoperative pneumonia. After determining the cut-off value for postoperative serum albumin, the patients were divided into two groups according to the minimum serum albumin level recorded during the first two postoperative days: group A included patients with a minimum serum album level less than 3.0 g/dL and group B included patients with a minimum serum album level of at least 3.0 g/dL. The prevalence of postoperative pneumonia was analysed using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) analyses.Results: The incidence of postoperative pneumonia following hip fracture surgery was 5.1% (n=59). Age, cardiovascular disease, and early postoperative hypoalbuminaemia during the first two postoperative days were independent risk factors for postoperative pneumonia. Early postoperative hypoalbuminaemia was associated with postoperative pneumonia development in the PSM and IPTW analyses (P = 0.016 and < 0.001, respectively).Conclusion: This study demonstrated that early postoperative hypoalbuminaemia is an independent risk factor for the development of postoperative pneumonia in patients undergoing hip fracture surgery.Keywords: osteoporosis, osteoporotic fracture, albumin, complication

Objective: This study aimed to develop a Korean version of the Nonsuicidal Self-injury Inventory (K-NSSI) through the Deliberate Self-harm Inventory (DSHI) developed by Gratz for the Korean context and confirm its reliability and validity for clinical application., Methods: A total of 188 participants were analyzed utilizing the DSHI, the Korean version of the Self-harm Inventory, the Personality Assessment Inventory-Borderline Features (PAI-BOR), and the DSM-5 Level-2-Depression scale (Level-2-Dep). Cronbach's α assessed their reliability, while frequency analysis examined the items of the K-NSSI scales. Validity of the K-NSSI was confirmed through correlation analyses between K-NSSI (tendency for and frequency of nonsuicidal self-injury [NSSI] behavior) and SHI, PAI-BOR total scale, four subscales of PAI-BOR, and Level-2-Dep scale. Polyserial correlations analyzed the correlation between the presence of NSSI behavior and other scales. Confirmatory factor analysis and structural equation modeling explored the relationship between borderline personality features and self-harm., Results: Cronbach's α was 0.71, indicating an "acceptable" level of reliability. Statistically significant correlations were observed between the presence of NSSI behavior and the total scores of SHI and PAI-BOR, and the four subscales of PAI-BOR. The frequency of NSSI showed statistically significant correlations with the total score of SHI and PAI-BOR, and its four subscales. Notably, 13.8% of participants reported engaging in self-harm behaviors, 26.9% reported a single occurrence, and 73.1% reported two or more instances. Structural equation modeling demonstrated that self-harm adequately predicted borderline personality traits., Conclusion: This study successfully validated the adaptation of DSHI into K-NSSI. The K-NSSI can facilitate interventions for self-harm incidents.

Microplastics, particularly those in the micrometer scale, have been shown to enter the human body through ingestion, inhalation, and dermal contact. Recent research indicates that microplastics can potentially impact the central nervous system (CNS) by crossing the blood-brain barrier (BBB). However, the exact mechanisms of their transport, uptake, and subsequent toxicity at BBB remain unclear. In this study, we evaluated the size-dependent uptake and cytotoxicity of polystyrene microparticles using an engineered BBB model. Our findings demonstrate that 0.2 μm polystyrene microparticles exhibit significantly higher uptake and transendothelial transport compared to 1.0 μm polystyrene microparticles, leading to increased permeability and cellular damage. After 24 h of exposure, permeability increased by 15.6-fold for the 0.2 μm particles and 2-fold for the 1.0 μm particles compared to the control. After 72 h of exposure, permeability further increased by 27.3-fold for the 0.2 μm particles and a 4.5-fold for the 1.0 μm particles compared to the control. Notably, microplastics administration following TNF-α treatment resulted in enhanced absorption and greater BBB damage compared to non-stimulated conditions. Additionally, the size-dependent toxicity observed differently between 2D cultured cells and 3D BBB models, highlighting the importance of testing models in evaluating environmental toxicity., (© 2024. The Author(s).)

Excessive invalid explorations at the beginning of training lead deep reinforcement learning process to fall into the risk of overfitting, further resulting in spurious decisions, which obstruct agents in the following states and explorations. This phenomenon is termed primacy bias in online reinforcement learning. This work systematically investigates the primacy bias in online reinforcement learning, discussing the reason for primacy bias, while the characteristic of primacy bias is also analyzed. Besides, to learn a policy generalized to the following states and explorations, we develop an online reinforcement learning framework, termed self-distillation reinforcement learning (SDRL), based on knowledge distillation, allowing the agent to transfer the learned knowledge into a randomly initialized policy at regular intervals, and the new policy network is used to replace the original one in the following training. The core idea for this work is distilling knowledge from the trained policy to another policy can filter biases out, generating a more generalized policy in the learning process. Moreover, to avoid the overfitting of the new policy due to excessive distillations, we add an additional loss in the knowledge distillation process, using L2 regularization to improve the generalization, and the self-imitation mechanism is introduced to accelerate the learning on the current experiences. The results of several experiments in DMC and Atari 100k suggest the proposal has the ability to eliminate primacy bias for reinforcement learning methods, and the policy after knowledge distillation can urge agents to get higher scores more quickly.

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (Kp) and the apparent permeability (Papp). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (M pro ) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo M pro -inhibitor screening platform to evaluate the efficacies of M pro inhibitors based on M pro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and M pro -cleavage sequence, mimicking in vivo viral replication process mediated by M pro . By measuring the proteolytic activity of M pro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of M pro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering M pro inhibitors and may accelerate the development of therapeutics against COVID-19., (© 2024. The Author(s).)

This report describes the direct electrolysis of treated wastewater (as a catholyte) to produce hydrogen and potentially reuse the water. To suppress the negative shift of the cathodic potential due to an increase in pH by the hydrogen evolution reaction (HER), the treated wastewater is acidified using the synergetic effect of protons generated from the bipolar membrane and inorganic precipitation occurred at the surface of the cathode during the HER. Natural seawater, as an accessible source for Mg 2+ ions, was added to the treated wastewater because the concentration of Mg 2+ ions contained in the original wastewater was too low for acidification to occur. The mixture of treated wastewater with seawater was acidified to pH 3, allowing the initial cathode potential to be maintained for more than 100 h. The amount of inorganic precipitates formed on the cathode surface is greater than that in the control case (adding 0.5 M NaCl instead of seawater) but does not adversely affect the cathodic potential and Faradaic efficiency for H 2 production. Additionally, it was confirmed that less organic matter was adsorbed to the inorganic deposits under acidic conditions. These indicate that acidification plays an important role in improving the performance and stability of low-grade water electrolysis. Considering that the treated wastewater is discharged near the ocean, acidification-based electrolysis of the effluent with seawater can be a water reuse technology for green hydrogen production, enhancing water resilience and contributing to the circular economy of water resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

An in vitro model, composed of the short-wavelength human opsins and rhodopsins, is created. Two types of photosensitive neural spheroids are transfected for selective reaction under bluish-purple and green lights. These are employed to two devices with intact neuron and neural-spheroid to study the interaction. By photostimulation, the photosensitive spheroid initiated photoactivation, and the signal generated from its body is transmitted to adjacent neural networks. Specifically, the signal traveled through the axon bundle in narrow gap from photosensitive spheroid to intact spheroid as an eye-to-brain model including optic nerve. The whole process with photosensitive spheroid is monitored by calcium ion detecting fluorescence images. The results of this study can be applied to examine vision restoration and novel photosensitive biological systems with spectral sensitivity., (© 2023 Wiley-VCH GmbH.)

Study Design: Retrospective Cohort Study., Objectives: To determine the predictive capability between the 5-factor modified frailty index (mFI-5) scores and adverse clinical and radiographic outcomes following single-level transforaminal lumbar interbody fusion (TLIF)., Methods: All patients over the age of 50 undergoing single-level open or minimally invasive TLIF from 2012 to 2021 with a minimum follow-up of 1 year were identified. Deformity, trauma, emergency, and tumor cases were excluded as were patients undergoing revision surgeries. An mFI-5 score was computed for each patient using a set of five factors which included hypertension requiring medication, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, and partially or fully dependent functional status. Univariate and multivariate logistic regression analysis were performed to evaluate the impact of mFI-5 scores on readmissions, reoperations, and postoperative complications., Results: 156 patients were included and grouped according to their level of frailty: no-frailty (mFI = 0, n = 67), mild frailty (mFI = 1, n = 59), and severe frailty (mFI = 2+, n = 30). Multivariate analysis found high levels of frailty (mFI = 2+) to be independent predictors of reoperation (OR: 16.9, CI: 2.7 - 106.9, P = .003) and related readmissions (OR = 16.5, CI: 2.6 - 102.7, P = .003) as compared to the no-frailty group. An mFI-5 score of 2+ was also predictive of any complication (OR = 4.5, CI: 1.4 - 14.3, P = .01) and adjacent segment disease (ASD) (OR = 12.5, CI: 1.2 - 134.0, P = .037)., Conclusion: High levels of frailty were predictive of related readmissions, reoperations, any complications, and ASD in older adult patients undergoing single-level TLIF., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Emami receives grants/research support from NuVasive. Dr. Hwang is a consultant for Stryker Spine. None of these are applicable to the current study. For the remaining authors, none were declared.

Introducing deep learning technologies into the medical image processing field requires accuracy guarantee, especially for high-resolution images relayed through endoscopes. Moreover, works relying on supervised learning are powerless in the case of inadequate labeled samples. Therefore, for end-to-end medical image detection with overcritical efficiency and accuracy in endoscope detection, an ensemble-learning-based model with a semi-supervised mechanism is developed in this work. To gain a more accurate result through multiple detection models, we propose a new ensemble mechanism, termed alternative adaptive boosting method (Al-Adaboost), combining the decision-making of two hierarchical models. Specifically, the proposal consists of two modules. One is a local region proposal model with attentive temporal-spatial pathways for bounding box regression and classification, and the other one is a recurrent attention model (RAM) to provide more precise inferences for further classification according to the regression result. The proposal Al-Adaboost will adjust the weights of labeled samples and the two classifiers adaptively, and the nonlabel samples are assigned pseudolabels by our model. We investigate the performance of Al-Adaboost on both the colonoscopy and laryngoscopy data coming from CVC-ClinicDB and the affiliated hospital of Kaohsiung Medical University. The experimental results prove the feasibility and superiority of our model.

Using biosensor to screen for Alzheimer's disease (AD) facilitates early detection of AD with high sensitivity and accuracy. This approach overcomes the limitations of conventional AD diagnostic methods, such as neuropsychological assessment and neuroimaging analysis. Here, we propose a simultaneous analysis of signal combinations generated by four crucial AD biomarkers (Amyloid beta 1-40 (Aβ 40 ), Aβ 42 , total tau 441 (tTau 441 ), and phosphorylated tau 181 (pTau 181 )) by inducing a dielectrophoretic (DEP) force on fabricated interdigitated microelectrode (IME) sensor. By applying an optimal DEP force, our biosensor selectively concentrates and filters the plasma-based AD biomarkers, exhibiting high sensitivity (limit of detection <100 fM) and selectivity in the plasma-based AD biomarkers detection (p < 0.0001). Consequently, it is demonstrated that a complex combined signal comprising four AD-specific biomarker signals (Aβ 40 - Aβ 42 + tTau 441 - pTau 181 ) can differentiate between patients with AD and healthy subjects with high accuracy (78.85%) and precision (80.95%) (p < 0.0001)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bisphenol F (BPF; 4,4'-dihydroxydiphenylmethane) is one of the most frequently used compounds in the manufacture of plastics and epoxy resins. Previous studies have demonstrated that BPF affects locomotor behavior, oxidative stress, and neurodevelopment in zebrafish. However, its neurotoxic effects are controversial, and the underlying mechanisms are unclear. In order to determine whether BPF affects the motor system, we exposed zebrafish embryos to BPF and assessed behavioral, histological, and neurochemical changes. Spontaneous locomotor behavior and startle response were significantly decreased in BPF-treated zebrafish larvae compared with control larvae. BPF induced motor degeneration and myelination defects in zebrafish larvae. In addition, embryonic exposure to BPF resulted in altered metabolic profiles of neurochemicals, including neurotransmitters and neurosteroids, which may impact locomotion and motor function. In conclusion, exposure to BPF has the potential to affect survival, motor axon length, locomotor activity, myelination, and neurochemical levels of zebrafish larvae.

Cholera is a highly contagious and lethal waterborne disease induced by an infection with Vibrio cholerae (V. cholerae) secreting cholera toxin (CTx). Cholera toxin subunit B (CTxB) from the CTx specifically binds with monosialo-tetra-hexosyl-ganglioside (GM1) found on the exterior cell membrane of an enterocyte. Bioinspired by the pathological process of CTx, we developed an electrochemical biosensor with GM1-expressing Caco-2 cell membrane (CCM) on the electrode surface. Briefly, the electrode surface was functionalized with CCM using the vesicle fusion method. We determined the CTxB detection performances of Caco-2 cell membrane-coated biosensor (CCB) using electrochemical impedance spectroscopy (EIS). the CCB had an excellent limit of detection of ∼11.46 nM and a detection range spanning 100 ng/mL - 1 mg/mL. In addition, the CCB showed high selectivity against various interfering molecules, including abundant constituents of intestinal fluid and various bacterial toxins. The long-term stability of the CCBs was also verified for 3 weeks using EIS. Overall, the CCB has excellent potential for practical use such as point-of-care and cost-effective testing for CTxB detection in developing countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Patients with Parkinson's disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinson's disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinson's disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology. Two separate cohorts of Parkinson's disease patients and controls were recruited from the Emory Movement Disorders Clinic and scanned on two different MRI scanners. In cohort 1, imaging data from 19 controls and 22 Parkinson's disease patients were acquired with a Siemens Trio 3 Tesla scanner using a 2D gradient echo sequence with magnetization transfer preparation pulse. Cohort 2 consisted of 33 controls and 39 Parkinson's disease patients who were scanned on a Siemens Prisma 3 Tesla scanner with a similar imaging protocol. Locus coeruleus and substantia nigra pars compacta volumes were segmented in both cohorts. Substantia nigra pars compacta volume (Cohort 1: p = 0.0148; Cohort 2: p = 0.0011) and locus coeruleus volume (Cohort 1: p = 0.0412; Cohort 2: p = 0.0056) were significantly reduced in the Parkinson's disease group as compared to controls in both cohorts. This imaging approach robustly detects Parkinson's disease effects on these structures, indicating that it is a promising marker for neurodegenerative neuromelanin loss., Competing Interests: Dr. Huddleston and Dr. Hu are inventors on an issued patent relating to the NM-MRI pulse sequence (US Patent number 9600881) and Dr. Huddleston is an inventor on a published patent application (US-2021/0007603-A1) relating to the image processing methods reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hwang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Context: Oblique lumbar interbody fusion (OLIF) and extreme lateral interbody fusion (XLIF) are 2 popular minimally invasive spinal fusion techniques with unique approach-related complication profiles. Accordingly, patient-specific anatomical factors, such as vascular anatomy or iliac crest height, greatly influence which technique to use. Previous studies comparing these approaches do not account for the inability of XLIF to access the L5-S1 disc space and therefore do not exclude this level in their analysis. The purpose of this study was to compare radiological and clinical outcomes of these techniques in the L1-L5 region., Methods: A query of 3 electronic databases (PubMed, CINAHL plus, and SCOPUS) was performed, without time restriction, to identify studies that evaluated outcomes of single-level OLIF and/or XLIF between L1 and L5. Based on heterogeneity, a random effects meta-analysis was performed to evaluate the pooled estimation of each variable between the groups. An overlap of 95% confidence intervals suggests no statistically significant difference at the p<.05 level., Results: A total of 1,010 patients (408 OLIF, 602 XLIF) were included from 24 published studies. Improvements in disc height (OLIF: 4.2 mm; XLIF: 5.3 mm), lumbar segmental (OLIF: 2.3°; XLIF: 3.1°), and lumbar lordotic angles (OLIF: 5.3°; XLIF: 3.3°) showed no significant difference. The rate of neuropraxia was significantly greater in the XLIF group at 21.2% versus 10.9% in the OLIF group (p<.05). However, the rate of vascular injury was higher in the OLIF cohort at 3.2% (95% CI:1.7-6.0) as compared to 0.0 (95% CI: 0.0-1.4) in the XLIF cohort. Improvements in VAS-b (OLIF: 5.6; XLIF: 4.5) and ODI (OLIF: 37.9; XLIF: 25.6) scores were not significantly different between the 2 groups., Conclusions: This meta-analysis demonstrates similar clinical and radiological outcomes between single-level OLIF and XLIF from L1 to L5. XLIF had significantly higher rates of neuropraxia, whereas OLIF had greater rates of vascular injury., Competing Interests: Dr. Emami receives grants/research support from NuVasive. Dr. Faloon receives grant and research support from Stryker Spine and Centinel Spine. Dr. Hwang is a consultant for Stryker Spine. None of these are applicable to the current study. For the remaining authors, none were declared.

Some researchers have introduced transfer learning mechanisms to multiagent reinforcement learning (MARL). However, the existing works devoted to cross-task transfer for multiagent systems were designed just for homogeneous agents or similar domains. This work proposes an all-purpose cross-transfer method, called multiagent lateral transfer (MALT), assisting MARL with alleviating the training burden. We discuss several challenges in developing an all-purpose multiagent cross-task transfer learning method and provide a feasible way of reusing knowledge for MARL. In the developed method, we take features as the transfer object rather than policies or experiences, inspired by the progressive network. To achieve more efficient transfer, we assign pretrained policy networks for agents based on clustering, while an attention module is introduced to enhance the transfer framework. The proposed method has no strict requirements for the source task and target task. Compared with the existing works, our method can transfer knowledge among heterogeneous agents and also avoid negative transfer in the case of fully different tasks. As far as we know, this article is the first work denoted to all-purpose cross-task transfer for MARL. Several experiments in various scenarios have been conducted to compare the performance of the proposed method with baselines. The results demonstrate that the method is sufficiently flexible for most settings, including cooperative, competitive, homogeneous, and heterogeneous configurations.

Objective: This study involved a meta-analysis of South Korean studies regarding psychosocial interventions for patients with breast cancer to provide basic data to support the development of an integrated healthcare service model., Methods: Randomized controlled studies with a pretest-posttest design were selected, and those presenting means, standard deviations, and standardized mean differences were included. For quality evaluation and heterogeneity testing, the Jadad scale and the Q-value and I2 were used. To estimate the effect size of each study, Hedge's g was used. Publication bias was analyzed with the Funnel plot and Egger's regression test., Results: Of the 28 studies selected for the, meta-analysis was performed on eight. The total number of datasets included in the meta-analysis was 33. The evaluation based on the Jadad scale revealed no significant inter-rater variation ( p = 0.35). The mean number of sessions was 7.93 and the mean intervention time was 13.2 hours. The interventions were mostly administered in a group structure (94%) and, regarding the type, they were categorized as integrated (36.4%), cognitive (30.3%), and meditation (24.2%). The mean effect size was 1.21 against no treatment group., Conclusion: The analyzed studies showed heterogeneity, with a corresponding asymmetry found on the Funnel plot. Despite the heterogeneity and publication bias, the mean effect size was significantly large. Cognitive interventions, meditation, and psychological education programs are expected to assist in reducing negative emotions and enhancing quality of life in patients with breast cancer.

The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson's disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

Although bisphenol F (BPF), the main replacement for bisphenol A, has been commonly used in polycarbonate production, its neurotoxicity and the underlying mechanisms remain poorly understood. To address this knowledge gap, this study aimed to assess the neurotoxicity caused by chronic exposure to BPF and to identify its underlying mechanisms. We exposed adult zebrafish chronically to BPF at environmentally relevant concentrations (0.001, 0.01, and 0.1 mg/L) for 4 weeks. The results revealed that with BPF crossing the blood-brain barrier and bioaccumulating in brain tissues, chronic exposure to BPF resulted in anxiety-like behaviors and disruptions in learning and memory function in adult zebrafish. Furthermore, BPF toxicity in the zebrafish brain involved the dysregulation of metabolic pathways for choline and kynurenine in neurotransmitter systems and for 17β-estradiol, cortisol, pregnenolone-sulfate, and Dehydroepiandrosterone (DHEA)-sulfate in neurosteroid systems. RNA-seq analysis revealed that BPF exposure affected metabolic pathways, calcium signaling pathways, neuroactive ligand-receptor interactions, tight junctions, gap junctions, and the gonadotropin-releasing hormone signaling pathway. Our results indicate that chronic exposure to BPF alters the neurochemical profile of the brain and causes neurobehavioral effects, such as anxiety and cognitive decline. Overall, the multimodal approach, including behavioral and neurochemical profiling technologies, has great potential for the comprehensive assessment of potential risks posed by environmental pollutants to human and ecosystem health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

This article presents a CMOS microelectrode array (MEA) system with a reconfigurable sub-array multiplexing architecture using the time-division multiplexing (TDM) technique. The system consists of 24,320 TiN electrodes with 17.7 μm-pitch pixels and 380 column-parallel readout channels including a low-noise amplifier, a programmable gain amplifier, and a 10-b successive approximation register analog to digital converter. Readout channels are placed outside the pixel for high spatial resolution, and a flexible structure to acquire neural signals from electrodes selected by configuring in-pixel memory is realized. In this structure, a single channel can handle 8 to 32 electrodes, guaranteeing a temporal resolution from 5 kS/s to 20 kS/s for each electrode. A 128 × 190 MEA system was fabricated in a 110-nm CMOS process, and each readout channel consumes 81 μW at 1.5-V supply voltage featuring input-referred noise of 1.48 μV rms without multiplexing and 5.4 μV rms with multiplexing at the action-potential band (300 Hz-10 kHz).

Introduction: Striatal dopamine transporter (DAT) imaging using 123 I-ioflupane single photon positron emitted computed tomography (SPECT) (DaTScan, GE) identifies 5-20% of newly diagnosed Parkinson's disease (PD) subjects enrolling in clinical studies to have scans without evidence of dopaminergic deficit (SWEDD). These individuals meet diagnostic criteria for PD, but do not clinically progress as expected, and they are not believed to have neurodegenerative Parkinsonism. Inclusion of SWEDD participants in PD biomarker studies or therapeutic trials may therefore cause them to fail. DaTScan can identify SWEDD individuals, but it is expensive and not widely available; an alternative imaging approach is needed. Here, we evaluate the use of neuromelanin-sensitive, iron-sensitive, and diffusion contrasts in substantia nigra pars compacta (SNpc) to differentiate SWEDD from PD individuals., Methods: Neuromelanin-sensitive, iron-sensitive, and diffusion imaging data for SWEDD, PD, and control subjects were downloaded from the Parkinson's progression markers initiative (PPMI) database. SNpc volume, SNpc iron ( R 2 ), and SNpc free water (FW) were measured for each participant., Results: Significantly smaller SNpc volume was seen in PD as compared to SWEDD ( P < 10 -3 ) and control ( P < 10 -3 ) subjects. SNpc FW was elevated in the PD group relative to controls ( P = 0.017). No group difference was observed in SNpc R 2 ., Conclusion: In conclusion, nigral volume and FW in the SWEDD group were similar to that of controls, while a reduction in nigral volume and increased FW were observed in the PD group relative to SWEDD and control participants. These results suggest that these MRI measures should be explored as a cost-effective alternative to DaTScan for evaluation of the nigrostriatal system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Langley, Hwang, Hu and Huddleston.)

Limited studies on neurotoxicity following chronic exposure to butyl‑paraben (BuP) have been conducted. In this study, neurobehavior in zebrafish adults was assessed using the novel tank test, photomotor response test, and T-maze test after exposure to BuP for 28 days at concentrations of 0, 0.01, 0.1, and 1.0 mg/L. To comprehensively understand the underlying molecular perturbations in the brain, alterations in transcripts, neurotransmitters, and neurosteroids were measured. We found that BuP penetrated the blood-brain barrier and impaired neurobehavior in photosensitivity at 1.0 mg/L and in memory at 0.1 and 1.0 mg/L. RNA-seq analysis showed that phototransduction, tight junctions, and neuroactive ligand receptor activity were significantly affected, which explains the observed abnormal neurobehaviors. Neurosteroid analysis revealed that BuP increased cortisol levels in a concentration-dependent manner and specifically reduced allopregnanolone levels at all tested concentrations, suggesting that cortisol and allopregnanolone are significant neurosteroid markers associated with photosensitivity and memory deficits. Collectively, we demonstrated that BuP can cross the blood-brain and modulate the levels of transcripts, associated with phototransduction and circadian rhythm, and neurosteroidal cortisol and allopregnanolone, resulting in abnormal neurobehavioral responses to light stimulation and learning and memory., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Viral infections cause damage to various organ systems by inducing organ-specific symptoms or systemic multi-organ damage. Depending on the infection route and virus type, infectious diseases are classified as respiratory, nervous, immune, digestive, or skin infections. Since these infectious diseases can widely spread in the community and their catastrophic effects are severe, identification of their causative agent and mechanisms underlying their pathogenesis is an urgent necessity. Although infection-associated mechanisms have been studied in two-dimensional (2D) cell culture models and animal models, they have shown limitations in organ-specific or human-associated pathogenesis, and the development of a human-organ-mimetic system is required. Recently, three-dimensional (3D) engineered tissue models, which can present human organ-like physiology in terms of the 3D structure, utilization of human-originated cells, recapitulation of physiological stimuli, and tight cell-cell interactions, were developed. Furthermore, recent studies have shown that these models can recapitulate infection-associated pathologies. In this review, we summarized the recent advances in 3D engineered tissue models that mimic organ-specific viral infections. First, we briefly described the limitations of the current 2D and animal models in recapitulating human-specific viral infection pathology. Next, we provided an overview of recently reported viral infection models, focusing particularly on organ-specific infection pathologies. Finally, a future perspective that must be pursued to reconstitute more human-specific infectious diseases is presented., Competing Interests: The authors declare they have no competing interests., (© 2022 The Authors.)

A lateral flow assay (LFA) platform is a powerful tool for point-of-care testing (POCT), especially for self-testing. Although the LFA platform provides a simple and disposable tool for Coronavirus disease of 2019 (COVID-19) antigen (Ag) and antibody (Ab) screening tests, the lower sensitivity for low virus titers has been a bottleneck for practical applications. Herein, we report the combination of a microfluidic paper-based nanoelectrokinetic (NEK) preconcentrator and an LFA platform for enhancing the sensitivity and limit of detection (LOD). Biomarkers were electrokinetically preconcentrated onto a specific layer using the NEK preconcentrator, which was then coupled with LFA diagnostic devices for enhanced performance. Using this nanoelectrokinetic-assisted LFA (NEK-LFA) platform for self-testing, the severe acute respiratory syndrome coronavirus 2 Immunoglobulin G (SARS-CoV-2 IgG) sample was preconcentrated from serum samples. After preconcentration, the LOD of the LFA was enhanced by 32-fold, with an increase in analytical sensitivity (16.4%), which may offer a new opportunity for POCT and self-testing, especially in the COVID-19 pandemic and endemic global context., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microplastics, small pieces of plastic derived from polystyrene, have recently become an ecological hazard due to their toxicity and widespread occurrence in aquatic ecosystems. In this study, we exposed zebrafish larvae to two types of fluorescent polystyrene nanoparticles (PS-NPs) to identify their size-dependent effects. PS-NPs of 50 nm, unlike 100 nm PS-NPs, were found to circulate in the blood vessels and accumulate in the brains of zebrafish larvae. Behavioral and electroencephalogram (EEG) analysis showed that 50 nm PS-NPs induce abnormal behavioral patterns and changes in EEG power spectral densities in zebrafish larvae. In addition, the quantification of endogenous neurochemicals in zebrafish larvae showed that 50 nm PS-NPs disturb dopaminergic metabolites, whereas 100 nm PS-NPs do not. Finally, we assessed the effect of PS-NPs on the permeability of the blood-brain barrier (BBB) using a microfluidic system. The results revealed that 50 nm PS-NPs have high BBB penetration compared with 100 nm PS-NPs. Taken together, we concluded that small nanoparticles disturb the nervous system, especially dopaminergic metabolites.

An ideal dye-based sensing array has essential design requirements, including facile preparation methodology, tolerance to water vapor, a broad range of color-responsive changes, and a simple readout system. Here, a brief synthetic route is developed for ion-pairing dyes exhibiting unusual chromatic changes across the entire visible spectrum. It requires only mixing and precipitation under mild conditions. The dyes are applied to a sensing array containing 12 sensing elements with different initial states. Owing to the numerous color variations of the dyes, the color map generated by the array is highly simple yet sufficiently accurate to distinguish among the different functional groups (such as amines, aldehydes, and carboxylic acids) as well as carbon chain lengths. Principle component analysis (PCA) demonstrates that volatile organic compounds (VOCs) can be well classified according to the color changes of the sensing array. The ion-pairing dyes are embedded into 3D stacked nanofibers via electrospinning, and function as effective harmful-gas (e.g., formaldehyde) sensors with sub-ppm theoretical detection limits (0.15 ppm). Finally, the 3D stacked nanofibers can be employed in an optoelectronic filter system that automatically checks for formaldehyde in the surroundings and also confirms the effective removal of the detected formaldehyde by the gas filter cartridge., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

A photoreceptor on the retina acts as an optical waveguide to transfer an individual photonic signal to the cell inside, which is determined by the refractive index of internal materials. Under the photoactivation of photoreceptors making conformational and chemical variation in a visual cell, the optical signal modulation is demonstrated using an artificial photoreceptor-based waveguide with a controlling beam refraction. Two types of nanodiscs are made of human photoreceptor proteins, short-wavelength-sensitive opsin and rhodopsin, with spectral sensitivity. The refractive index and nonlinear features of those two photosensitive nanodiscs are investigated as fundamental properties. The photonanodiscs are photoactivated in such a way that allow refractive index tuning over 0.18 according to the biological function of the respective proteins with color-dependent response.

Background: Shoulder subluxation occurs in 17−64% of hemiplegic patients after stroke and develops mostly during the first three weeks of hemiplegia. A range of shoulder orthoses has been used in rehabilitation to prevent subluxation. However, there is little evidence of their efficacy. AIM: This study aimed to investigate whether there is a difference in the subluxation distance, pain, and functional level of the hemiplegic upper extremity among patients with two different shoulder orthoses. Design: This is a prospective, randomized controlled trial with intention-to-treat analysis. SETTING: Multicenter, rehabilitation medicine department of two university hospitals in South Korea. Population: Forty-one patients with subacute stroke with shoulder subluxation with greater than 0.5 finger width within 4 weeks of stroke were recruited between January 2016 and October 2021. Methods: The experimental group used an elastic dynamic sling while sitting and standing to support the affected arm for eight weeks. The control group used a Bobath sling while sitting and standing. The primary outcome was to assess the distance of the shoulder subluxation on radiography. The secondary outcomes were upper-extremity function, muscle power, activities of daily living, pain and spasticity. Result: The horizontal distance showed significant improvement in the elastic dynamic sling group, but there were no significant differences in the vertical distance between the elastic dynamic and Bobath sling groups. Both groups showed improvements in upper-extremity movements and independence in daily living after 4 and 8 weeks of using shoulder orthoses, and the differences within the groups were significant (p < 0.05). However, there were no significant differences in upper-extremity movements and independence in daily living between the two groups. Conclusions: The subluxation distance showed better results in the elastic dynamic sling, which has both proximal and distal parts, than in the Bobath sling, which holds only the proximal part. Both shoulder orthoses showed improvements in the modified Barthel index, upper-extremity function, and manual muscle testing.

Metacognitive deficits affect Alzheimer's disease (AD) patient safety and increase caregiver burden. The brain areas that support metacognition are not well understood. 112 participants from the Imaging and Genetic Biomarkers for AD (ImaGene) study underwent comprehensive cognitive testing and brain magnetic resonance imaging. A performance-prediction paradigm was used to evaluate metacognitive abilities for California Verbal Learning Test-II learning (CVLT-II 1-5) and delayed recall (CVLT-II DR); Visual Reproduction-I immediate recall (VR-I Copy) and Visual Reproduction-II delayed recall (VR-II DR); Rey-Osterrieth Complex Figure Copy (Rey-O Copy) and delayed recall (Rey-O DR). Vertex-wise multivariable regression of cortical thickness was performed using metacognitive scores as predictors while controlling for age, sex, education, and intracranial volume. Subjects who overestimated CVLT-II DR in prediction showed cortical atrophy, most pronounced in the bilateral temporal and left greater than right (L > R) frontal cortices. Overestimation of CVLT-II 1-5 prediction and DR performance in postdiction showed L > R associations with medial, inferior and lateral temporal and left posterior cingulate cortical atrophy. Overconfident prediction of VR-I Copy performance was associated with right greater than left medial, inferior and lateral temporal, lateral parietal, anterior and posterior cingulate and lateral frontal cortical atrophy. Underestimation of Rey-O Copy performance in prediction was associated with atrophy localizing to the temporal and cingulate areas, and in postdiction, with diffuse cortical atrophy. Impaired metacognition was associated to cortical atrophy. Our results indicate that poor insight into one's cognitive abilities is a pervasive neurodegenerative feature associated with AD across the cognitive spectrum., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paraquat is a polar herbicide protecting plant products against invasive species, it requires careful manipulation and restricted usage because of its harmful potentials. Exposure to paraquat triggers oxidative damage in dopaminergic neurons and subsequently causes a behavioral defect in vivo. Thereby, persistent exposure to paraquat is known to increase Parkinson's disease risk by dysregulating dopaminergic systems in humans. Therefore, most studies have focused on the dopaminergic systems to elucidate the neurotoxicological mechanism of paraquat poisoning, and more comprehensive neurochemistry including histaminergic, serotonergic, cholinergic, and GABAergic systems has remained unclear. Therefore, in this study, we investigated the toxicological potential of paraquat poisoning using a variety of approaches such as toxicokinetic profiles, behavioral effects, neural activity, and broad-spectrum neurochemistry in zebrafish larvae after short-term exposure to paraquat and we performed the molecular modeling approach. Our results showed that paraquat was slowly absorbed in the brain of zebrafish after oral administration of paraquat. In addition, paraquat toxicity resulted in behavioral impairments, namely, reduced motor activity and led to abnormal neural activities in zebrafish larvae. This locomotor deficit came with a dysregulation of dopamine synthesis induced by the inhibition of tyrosine hydroxylase activity, which was also indirectly confirmed by molecular modeling studies. Furthermore, short-term exposure to paraquat also caused simultaneous dysregulation of other neurochemistry including cholinergic and serotonergic systems in zebrafish larvae. The present study suggests that this neurotoxicological profiling could be a useful tool for understanding the brain neurochemistry of neurotoxic agents that might be a potential risk to human and environmental health., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An increasing number of patients are suffering from central nervous system (CNS) injury, including spinal cord injury. However, no suitable treatment is available for such patients as yet. Various platforms have been utilized to recapitulate CNS injuries. However, animal models and in vitro two-dimensional (2D)-based cell culture platforms have limitations, such as genetic heterogeneity and loss of the neural-circuit ultrastructure. To overcome these limitations, we developed a method for performing axotomy on an open-access three-dimensional (3D) neuron-culture platform. In this platform, the 3D alignment of axons in the brain tissue was recapitulated. For direct access to the cultured axons, the bottom of the 3D neuron-culture device was disassembled, enabling exposure of the neuron-laden Matrigel to the outside. The mechanical damage to the axons was recapitulated by puncturing the neuron-laden Matrigel using a pin. Thus, precise axotomy of three-dimensionally aligned axons could be performed. Furthermore, it was possible to fill the punctuated area by re-injecting Matrigel. Consequently, neurites regenerated into re-injected Matrigel. Moreover, it was confirmed that astrocytes can be co-cultured on this open-access platform without interfering with the axon alignment. The proposed open-access platform is expected to be useful for developing treatment techniques for CNS injuries.

The tumor microenvironment (TME) is the environment around the tumor, including blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix (ECM). Owing to its component interactions, the TME influences tumor growth and drug delivery in a highly complex manner. Although several vascularized cancer models are developed to mimic the TME in vitro, these models cannot comprehensively reflect blood vessel-tumor spheroid interactions. Here, a method for inducing controlled tumor angiogenesis by engineering the microenvironment is presented. The interstitial flow direction regulates the direction of capillary sprouting, showing that angiogenesis occurs in the opposite direction of flow, while the existence of lung fibroblasts affects the continuity and lumen formation of sprouted capillaries. The vascularized tumor model shows enhanced delivery of anticancer drugs and immune cells to the tumor spheroids because of the perfusable vascular networks. The possibility of capillary embolism using anticancer drug-conjugated liquid metal nanoparticles is investigated using the vascularized tumor model. This vascularized tumor platform can aid in the development of effective anticancer drugs and cancer immunotherapy., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Colorimetric glucose sensors using enzyme-coronated gold nanoparticles have been developed for high-throughput assays to monitor the blood glucose levels of diabetic patients. Although those sensors have shown sensitivity and wide linear detection ranges, they suffer from poor selectivity and stability in detecting blood glucose, which has limited their practical use. To address this limitation, herein, we functionalized glucose-oxidase-coronated gold nanoparticles with an erythrocyte membrane (EM-GOx-GNPs). Because the erythrocyte membrane (EM) selectively facilitates the permeation of glucose via glucose transporter-1 (GLUT1), the functionalization of GOx-GNPs with EM improved the stability, selectivity (3.3- to 15.8-fold higher), and limit of detection (LOD). Both membrane proteins, GLUT1 and aquaporin-1 (AQP1), on EM were shown to be key components for selective glucose detection by treatment with their inhibitors. Moreover, we demonstrated the stability of EM-GOx-GNPs in high-antioxidant-concentration conditions, under long-term storage (∼4 weeks) and a freeze-thaw cycle. Selectivity of the EM-GOx-GNPs against other saccharides was increased, which improved the LOD in phosphate-buffered saline and human serum. Our results indicated that the functionalization of colorimetric glucose sensors with EM is beneficial for improving selectivity and stability, which may make them candidates for use in a practical glucose sensor.

The literature has shown the importance of long-term follow-up for adults with scoliosis treated surgically because complication and revision rates are high. The goal of this study was to determine long-term outcomes and complications of lateral lumbar interbody fusion (LLIF) with posterior instrumentation for adult patients with scoliosis. A retrospective review of our institution's database was performed to identify adult patients with scoliosis treated with LLIF between 2008 and 2013 with a minimum follow-up of 4 years. Medical records were reviewed for complications and revisions. Pre- and postoperative deformity Cobb angle measurements were taken as well as pelvic incidence (PI) and lumbar lordosis (LL). Functional outcome scores, including Oswestry Disability Index and visual analog scale score for back and leg pain, were assessed preoperatively and at follow-up. Standard binomial and categorical comparative analysis was performed. The 26 patients included had a mean age of 62 years, mean follow-up of 89 months, and mean of 1.8 levels per operation. Four patients (15.4%) required revisions. Mean deformity Cobb angle was 26° preoperatively and 14° postoperatively. Mean PI-LL mismatch was 11.7° preoperatively and 5.9° postoperatively. Nineteen (73%) patients had a PI-LL mismatch greater than 10° preoperatively, whereas only 2 (7.7%) had a mismatch postoperatively. Improvement was seen in all functional outcome scores. Long-term clinical results of LLIF for adults with deformity showed a low proportion of revision in the treatment of a condition with an established high rate of revision. The ability to reduce pelvic mismatch may further reduce the rate of revision. In this study, LLIF resulted in improved functional outcomes and patient satisfaction. [ Orthopedics . 2022;45(3):e134-e139.].

Osteoporosis affects millions of people worldwide. As such, this study assessed the macrophage-dependent in vitro anti-osteoporosis, phytochemical profile and hepatotoxicity effects in zebrafish larvae of the stem bark extracts of P. africana. Mouse bone marrow macrophages (BMM) cells were plated in 96-well plates and treated with P. africana methanolic bark extracts at concentrations of 0, 6.25, 12.5, 25, and 50 µg/ml for 24 h. The osteoclast tartrate-resistant acid phosphatase (TRAP) activity and cell viability were measured. Lipopolysaccharides (LPS) induced Nitrite (NO) and interleukin-6 (IL-6) production inhibitory effects of P. africana bark extracts (Methanolic, 150 µg/ml) and β-sitosterol (100 µM) were conducted using RAW 264.7 cells. Additionally, inhibition of IL-1β secretion and TRAP activity were determined for chlorogenic acid, catechin, naringenin and β-sitosterol. For toxicity study, zebrafish larvae were exposed to different concentrations of 25, 50, 100, and 200 µg/ml P. africana methanolic, ethanolic and water bark extracts. Dimethyl sulfoxide (0.05%) was used as a negative control and tamoxifen (5 µM) and dexamethasone (40 µM or 80 µM) were positive controls. The methanolic P. africana extracts significantly inhibited (p < 0.001) TRAP activity at all concentrations and at 12.5 and 25 µg/ml, the extract exhibited significant (p < 0.05) BMM cell viability. NO production was significantly inhibited (all p < 0.0001) by the sample. IL-6 secretion was significantly inhibited by P. africana methanolic extract (p < 0.0001) and β-sitosterol (p < 0.0001) and further, chlorogenic acid and naringenin remarkably inhibited IL-1β production. The P. africana methanolic extract significantly inhibited RANKL-induced TRAP activity. The phytochemical study of P. africana stem bark revealed a number of chemical compounds with anti-osteoporosis activity. There was no observed hepatocyte apoptosis in the liver of zebrafish larvae. In conclusion, the stem bark of P. africana is non-toxic to the liver and its inhibition of TRAP activity makes it an important source for future anti-osteoporosis drug development., (© 2022. The Author(s).)

For decades, acetylcholine (Ach) has been considered a critical biomarker for several degenerative brain diseases, including Alzheimer's, Parkinson's disease, Huntington's disease, and schizophrenia. Here, we propose a wafer-scale fabrication of polyaniline (PAni)-grafted graphene-based field-effect transistors (PGFET) and their biosensing applications for highly sensitive and reliable real-time monitoring of Ach in flow configuration. The grafted PAni provides suitable electrostatic binding sites for enzyme immobilization and enhances the pH sensitivity (2.68%/pH), compared to that of bare graphene-FET (1.81%/pH) for a pH range of 3-9 without any pH-hysteresis. We further evaluated the PGFET's sensing performance for Ach detection with a limit of detection at the nanomolar level and significantly improved sensitivity (~103%) in the concentration range of 108 nM to 2 mM. Moreover, the PGFET exhibits excellent selectivity against various interferences, including glucose, ascorbic acid, and neurotransmitters dopamine and serotonin. Finally, we investigated the effects of an inhibitor (rivastigmine) on the AchE activity of the PGFET. From the results, we demonstrated that the PGFET has great potential as a real-time drug-screening platform by monitoring the inhibitory effects on enzymatic activity.

Study Design: Retrospective cohort study., Objective: To compare minimally invasive posterior cervical foraminotomy (MI-PCF) and anterior cervical discectomy and fusion (ACDF) in the treatment of unilateral cervical radiculopathy., Summary of Background Data: MI-PCF has been shown to be equally effective as ACDF in treating cervical radiculopathy due to foraminal stenosis and similar pathologies. Additionally, it has been hypothesized that preserving motion and avoiding fusion reduces risk for adjacent segment disease, but potentially increases risk for subsequent revision to an ACDF. With similar short-term outcomes and substantial advantages, MI-PCF may be an effective alternative to ACDF for addressing appropriate cervical pathology., Methods: A retrospective review was performed to identify patients between 2009 and 2013 who underwent ACDF or MI-PCF with a minimum follow-up of 7 years. Demographic data was recorded. Revision rates and average time to revision between cohorts were compared. Clinical outcomes were assessed at each follow-up visit with Neck Disability Index and Visual Analog Scale for neck and Visual Analog Scale for arm pain scores. All complications were reviewed. Standard binomial and categorical comparative analysis were performed., Results: A total of 251 consecutive patients were included (205 ACDF, 46 MI-PCF). Mean follow-ups for the ACDF and MI-PCF groups were 98.3 and 95.9 months, respectively. Complication rates were 2.9% and 2.2% for the ACDF and MI-PCF cohorts, respectively (P = 0.779). Revision rates were 7.8% for the ACDF cohort and 8.7% for the MI-PCF cohort (P = 0.840). Both cohorts experienced significant improvements in their clinical scores compared with their preoperative values. Final Visual Analog Scale for neck pain (ACDF: 2.6; MI-PCF: 1.6) and Visual Analog Scale for arm pain (ACDF: 1.1; MI-PCF: 0.4) scores differed significantly at final follow-up (P =  < 0.001; P =  < 0.001)., Conclusion: MI-PCF is a safe and effective alternative to ACDF in the treatment of cervical radiculopathy, demonstrating substantial benefit. After final follow-up, MI-PCF demonstrated superior improvements in Visual Analog Scale scores, without increased complication or revision rates.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Single nucleotide polymorphisms (SNPs) that can alter phenotypes of individuals play a pivotal role in disease development and, more importantly, responses to therapy. However, SNP genotyping has been challenging due to the similarity of SNP alleles and their low concentration in biological samples. Sequence-specific nanoparticle with interpretative toehold-mediated sequence decoding in hydrogel (SWITCH) for multiplex SNP genotyping is presented. The encoding with gold nanoparticle probes transduces each SNP target to ≈1000 invaders with prominently different sequences between wild and mutant types, featuring polymerase chain reaction (PCR)-free amplification. Subsequently, the toehold-mediated DNA replacement in hydrogel microparticles decodes the invaders via SNP-specific fluorescence signals. The 4-plex detection of the warfarin-associated SNP targets spiked in commercially validated human serum (S1-100ML, Merck) is successfully demonstrated with excellent specificity. This work is the first technology development presenting PCR-free, multiplex SNP genotyping with a single reporting fluorophore, to the best of knowledge., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Biogas is an environmentally friendly and sustainable energy resource that can substitute or complement conventional fossil fuels. For practical uses, biogas upgrading, mainly through the effective separation of CO 2 (0.33 nm) and CH 4 (0.38 nm), is required to meet the approximately 90-95% purity of CH 4 , while CO 2 should be concomitantly purified. In this study, a high CO 2 perm-selective zeolite membrane was synthesized by heteroepitaxially growing a chabazite (CHA) zeolite seed layer with a synthetic precursor that allowed the formation of all-silica deca-dodecasil 3 rhombohedral (DDR) zeolite (with a pore size of 0.36 × 0.44 nm 2 ). The resulting hydrophobic DDR@CHA hybrid membrane on an asymmetric α-Al 2 O 3 tube was thin (ca. 2 μm) and continuous, thus providing both high flux and permselectivity for CO 2 irrespective of the presence or absence of water vapor (the third largest component in the biogas streams). To the best of our knowledge, the CO 2 permeance of (2.9 ± 0.3) × 10 -7 mol m -2 s -1 Pa -1 and CO 2 /CH 4 separation factor of ca. 274 ± 73 at a saturated water vapor partial pressure of ca. 12 kPa at 50 °C have the highest CO 2 /CH 4 separation performance yet achieved. Furthermore, we explored the membrane module properties of the hybrid membrane in terms of the recovery and purity of both CO 2 and CH 4 under dry and wet conditions. Despite the high intrinsic membrane properties of the current hybrid membrane, reflected by the high permeance and SF, the corresponding module properties indicated that high-performance separation of CO 2 and CH 4 for the desired biogas upgrading was achieved at a limited processing capacity. This supports the importance of understanding the correlation between the membrane and module properties, as this will provide guidance for the optimal operating conditions.

Cell-type-specific, activity-dependent electrophysiology can allow in-depth analysis of functional connectivity inside complex neural circuits composed of various cell types. To date, optics-based fluorescence recording devices enable monitoring cell-type-specific activities. However, the monitoring is typically limited to a single brain region, and the temporal resolution is significantly low. Herein, a multimodal multi-shank fluorescence neural probe that allows cell-type-specific electrophysiology from multiple deep-brain regions at a high spatiotemporal resolution is presented. A photodiode and an electrode-array pair are monolithically integrated on each tip of a minimal-form-factor silicon device. Both fluorescence and electrical signals are successfully measured simultaneously in GCaMP6f expressing mice, and the cell type from sorted neural spikes is identified. The probe's capability of combined electro-optical recordings for cell-type-specific electrophysiology at multiple brain regions within a neural circuit is demonstrated. The new experimental paradigm to enable the precise investigation of functional connectivity inside and across complex neural circuits composed of various cell types is expected., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Given the shift toward value-based healthcare, strategies that decrease risk in commonly performed procedures such as anterior cervical discectomy and fusion (ACDF) are of interest. The objective of this study was to analyze the effect of a two-attending surgeon team on the outcomes of patients undergoing single-level ACDF. A retrospective matched-cohort study of patients undergoing single-level ACDF for degenerative cervical spondylosis, with minimum 2-year follow-up was performed. Patients were subdivided into two cohorts: cases with procedures performed by one attending surgeon assisted by a resident physician and cases with procedures performed by an attending surgeon with another attending surgeon as first-assist. Patients were matched by age, sex, body mass index, smoking status, American Society of Anesthesia grade and Charlson Comorbidity Index. Perioperative data and complications were compared. Standard binomial and categorical comparative analysis were performed. Forty-two patients were included (21 in each group). There were 22 males and 20 females, with a mean age of 47.7 years and mean follow-up of 43.4 months. There were no differences in any demographic variable between groups, indicating successful matching. Cohort B had decreased anesthesia time (114.9 vs. 157.1 minutes, P < 0.001), operative time (58.1 vs. 98.9 minutes, P < 0.001) and blood loss (14.8 vs. 24.3 mL, P = 0.012). There were no significant differences in terms of post-operative complications including dysphagia, wound infection, neurologic or cardiovascular related complications. A two-attending surgeon team significantly reduces anesthesia time, surgical time, and blood loss in single-level ACDF procedures without an increase in complications or a decrease in fusion rates.

Analysis of a ratio between amyloid beta 1-40 and 1-42 (Aβ 1-40 and Aβ 1-42 ) presented in plasm enables a highly accurate diagnosis of Alzheimer's disease (AD). However, the analysis of plasma Aβs is not routinely conducted because of the lack of Aβ detection techniques sensitive enough to specifically detect Aβ from thousands of biomaterials present in the plasma. We developed a hydrogel-patterned spiral microelectrode sensor combined with a hopping dielectrophoretic (DEP) force, combining the negative DEP and positive DEP forces, for Aβ detection. The hydrogel effectively increased the number of immobilized fragmented antibodies in the reaction region of the sensor and enabled size-exclusive passive filtration of non-specific plasma proteins from that region. The hopping DEP force further concentrated the Aβs and removed the non-specific plasma proteins. Consequently, our sensor achieved a limit of detection (LOD) of approximately ∼ 0.15 pg/mL for both Aβ 1-40 and Aβ 1-42 in the standard plasma. Finally, comparing the ratio between Aβ 1-40 and Aβ 1-42 signals, we distinguished AD patients from cognitively normal subjects with 95.83% accuracy and 92.31% precision (n = 24, p < 0.0001, One-way ANOVA)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Review of data from multiple sources is often necessary to determine cause of death for stillbirths and neonatal deaths, especially in low- to middle-income countries (LMICs) where available data may vary. The minimally invasive tissue sampling (MITS) procedure provides granular histologic and microbiologic data that clinical reports and verbal autopsies cannot provide. Expert panel evaluation of data from individual deaths can be resource-intensive but remains essential to accurately infer causes of death., Methods: The Project to Understand and Research Preterms and Stillbirths in South Asia (PURPOSe) study uses review panels to evaluate causes of death in 2 LMICs. To make the process manageable, a subset of the study variables was selected with professional input and organized into case reports. Case reports include clinical information, laboratory results, fetal or neonatal organ histology and polymerase chain reaction results from tissue obtained by MITS. Panelists evaluated the complete case report forms and then determined the cause of death based on available data., Results: Computerized case reports averaged 2 to 3 pages. Approximately 6 to 8 cases were reviewed and discussed per 1-hour panel meeting. All panelists were provided the same information; missing data were noted. This limited bias between panelists and across meetings. Study teams notably took ownership of data quality., Conclusions: Standardized case reports for cause-of-death determination panel evaluation improve the efficiency of the review process, clarify available information, and limit bias across panelists, time, and location., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)