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Abstract Objective Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients. Methods We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti‐seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains. Results A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12‐q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood‐onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies. Significance Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early‐onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background. Plain Language Summary This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood‐onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.

Abstract Objective Motorcyclists face a higher risk of severe morbidity and mortality compared to automobile passengers. This study aimed to determine the injury characteristics of motorcyclists according to their body mass index (BMI). Methods A retrospective observational cross‐sectional study was conducted using data from the Emergency Department‐based Injury In‐depth Surveillance (EDIIS) registry. Motorcycle riders aged 18 or older who were injured and admitted to study hospitals between 2019 and 2020 were included. Patients were divided into three groups based on BMI cutoffs of 18.5 and 25 kg/m2: the low, optimal, and high BMI groups. The primary outcome was anatomical injury location according to the abbreviated injury scale. The secondary outcomes were the surgery and intensive care unit admission rate, and the 48‐h and 30‐day in‐hospital mortality. Multivariable logistic regression analysis was performed to assess the impact of BMI on outcomes. Results Among 1280 patients, the low and high BMI groups had higher risk of abdominal injuries (AIS ≥ 2) than the optimal BMI group, with adjusted odds ratios of 2.82 (95% CI 1.41–5.63) and 1.61 (95% CI 1.17–2.21), respectively. Only the low BMI group had a significant association with severe abdominal injury (AIS ≥ 3), with an adjusted odds ratio of 3.11 (95% CI 1.31–7.39). No significant association was found between BMI and surgery, ICU admission, or mortality. Conclusion The low BMI group was more likely to have an abdominal injury (AIS score ≥2 or AIS score ≥3) during motorcycle injuries. BMI was not associated with surgery, ICU admission, or mortality.

Abstract Objectives We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). Materials and Methods From EGC patients who underwent ESD, bulk RNA sequencing was performed on non‐cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially‐expressed genes were identified, from which biomarkers were selected using real‐time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. Results From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p

Abstract Objective Despite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as “insufficient” or “sufficient” by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values. Results A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L. Interpretation This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia‐related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Abstract Introduction Ovarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe‐associated teratomas and non‐encephalitic control teratomas. Materials and Methods A prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole‐exome sequencing data and pathologic findings between NMDARe‐associated teratomas and control teratomas. Results We found 18 NMDARe‐associated teratomas from 15 patients and compared them with 17 non‐encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non‐encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non‐encephalitic teratomas (n = 18). However, rituximab‐naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non‐encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab‐treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab‐naïve encephalitic teratomas (P = 0.048 and 0.023, respectively). Discussion These results suggest that the initiation of immunopathogenesis in NMDARe‐associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma.

Abstract High‐capacity silicon (Si) materials hold a position at the forefront of advanced lithium‐ion batteries. The inherent potential offers considerable advantages for substantially increasing the energy density in batteries, capable of maximizing the benefit by changing the paradigm from nano‐ to micron‐sized Si particles. Nevertheless, intrinsic structural instability remains a significant barrier to its practical application, especially for larger Si particles. Here, a covalently interconnected system is reported employing Si microparticles (5 µm) and a highly elastic gel polymer electrolyte (GPE) through electron beam irradiation. The integrated system mitigates the substantial volumetric expansion of pure Si, enhancing overall stability, while accelerating charge carrier kinetics due to the high ionic conductivity. Through the cost‐effective but practical approach of electron beam technology, the resulting 500 mAh‐pouch cell showed exceptional stability and high gravimetric/volumetric energy densities of 413 Wh kg−1, 1022 Wh L−1, highlighting the feasibility even in current battery production lines.

Abstract Electroencephalogram (EEG) datasets from epilepsy patients have been used to develop seizure detection and prediction algorithms using machine learning (ML) techniques with the aim of implementing the learned model in a device. However, the format and structure of publicly available datasets are different from each other, and there is a lack of guidelines on the use of these datasets. This impacts the generatability, generalizability, and reproducibility of the results and findings produced by the studies. In this narrative review, we compiled and compared the different characteristics of the publicly available EEG datasets that are commonly used to develop seizure detection and prediction algorithms. We investigated the advantages and limitations of the characteristics of the EEG datasets. Based on our study, we identified 17 characteristics that make the EEG datasets unique from each other. We also briefly looked into how certain characteristics of the publicly available datasets affect the performance and outcome of a study, as well as the influences it has on the choice of ML techniques and preprocessing steps required to develop seizure detection and prediction algorithms. In conclusion, this study provides a guideline on the choice of publicly available EEG datasets to both clinicians and scientists working to develop a reproducible, generalizable, and effective seizure detection and prediction algorithm.

Abstract Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T‐cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD‐1, PD‐L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD‐L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD‐1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD‐1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p

Abstract Recent advances in autonomous systems have prompted a strong demand for the next generation of adaptive structures and materials to possess built‐in intelligence in their mechanical domain, the so‐called mechano‐intelligence (MI). Previous MI attempts mainly focused on specific case studies and lacked a systematic foundation in effectively and efficiently constructing and integrating different intelligent functions. Here, a new approach is uncovered to create multifunctional MI in adaptive structures using physical reservoir computing (PRC). That is, to concurrently embody computing power and the key elements of intelligence, namely perception, decision‐making, and commanding, directly in the mechanical domain, advancing from conventional reliance on add‐on computers and massive electronics. As an exemplar platform, a mechanically intelligent phononic metastructure is developed by harnessing its high‐degree‐of‐freedom nonlinear dynamics as PRC power. Through analyses and experiments, multiple intelligent structural functions are demonstrated ranging from self‐tuning wave controls to wave‐based logic gates. This research provides the much‐needed basis for creating future smart structures and materials that greatly surpass the state of the art—such as lower power consumption, more direct interactions, and better survivability in harsh environments or under cyberattacks. Moreover, it enables the addition of new functions and autonomy to systems without overburdening the onboard computers.

Abstract Recent advances in multistable metamaterials reveal a link between structural configuration transition and Boolean logic, heralding a new generation of computationally capable intelligent materials. To enable higher‐level computation, existing computational frameworks require the integration of large‐scale networked logic gates, which places demanding requirements on the fabrication of materials counterparts and the propagation of signals. Inspired by cellular automata, a novel computational framework based on multistable origami metamaterials by incorporating reservoir computing is proposed, which can accomplish high‐level computation tasks without the need to construct a logic gate network. This approach thus eliminates the demanding requirements for the fabrication of materials and signal propagation when constructing large‐scale networks for high‐level computation in conventional mechanical logic. Using the multistable stacked Miura‐origami metamaterial as a validation platform, digit recognition is experimentally implemented by a single actuator. Moreover, complex tasks, such as handwriting recognition and 5‐bit memory tasks, are also shown to be feasible with the new computation framework. The research represents a significant advancement in developing a new generation of intelligent materials with advanced computational capabilities. With continued research and development, these materials can have a transformative impact on a wide range of fields, from computational science to material mechano‐intelligence technology and beyond.

Abstract The design of an optimal non‐orthogonal multiple access (NOMA) transmission scheme with finite alphabet inputs for a typical two‐user uplink wireless communication system is investigated in which each terminal is equipped with a single antenna. Each of the two users utilises a four quadrature amplitude modulation (4‐QAM) constellation to transmit information data to a common base station, and the receiver employs a maximum likelihood (ML) detector to jointly estimate both transmitted signals. Assuming the availability of channel state information at both the transmitters and the receiver, it is aimed to design a pair of scalar beamformers for the two users such that the minimum Euclidean distance between elements of the received sum‐constellation is maximised subject to the power constraints on the users. A thorough consideration of all the different conditions results in the derivation of a closed‐form optimal beamformer design. As well, examination of the construction of sum‐constellation resulted from the optimum design directly leads to the unique decoding of the original transmitted signal of each user. To facilitate practical implementation, a fast decoding procedure of the optimum NOMA scheme is further developed. The corresponding theoretic probability of ML detection error is also derived. The theoretical development of an optimum sum‐constellation for the basic 2‐user 4‐QAM system provides a solid platform for the derivation of an optimum sum‐constellation for a K‐user and/or M‐QAM system. Indeed, a simple development of the basic sum‐constellation map facilitates such extensions. Numerical simulations not only demonstrate that the performance of the fast decoder agrees closely with the theoretical analysis, but also verify that it is superior in performance to other existing NOMA designs for the same system under high signal‐to‐noise ratio.

Abstract Objective Familial cerebral cavernous malformation (FCCM) is an autosomal dominant disease induced by loss‐of‐function mutations in three CCM genes, KRIT1, CCM2, and PDCD10. However, previous studies paid little attention to analyzing the radiologic features and age‐related disease burden according to the genes. Therefore, we retrospectively reviewed the genetic tests of our center's clinical FCCM patients. Method This study investigated clinical FCCM patients with multiple lesions or a family history of CCMs who underwent the FCCM gene (KRTI1, CCM2, and PDCD10) panel test. The clinical, genetic, and radiologic features were analyzed. Result Among the patients (n = 34) undergoing the FCCM gene test, twenty‐seven patients had CCM confirmed by brain MRI, and twenty‐one patients were considered to have FCCM (cohort 1). In cohort 1, thirteen patients had mutations in the FCCM gene, but eight did not. Cohort 2 comprised cohort 1 and four family members with the same mutation as the probands. Six novel variants in CCM genes were detected (KRIT1 c.22_26del, c.815dup, c.1094_1098del, c.1147‐2A>G, c.2124dup, and PDCD10 c.150 + 1dup). Cohort 1 demonstrated that brainstem lesions were mostly associated with the mutation detection in CCM genes (brainstem, lateral temporal, and parietal lesions vs. lateral temporal and parietal lesions, AUC 0.928 vs. 0.779, P = 0.0389). The radiologic severity worsened according to age in the KRIT1 group compared with the Mutation not detected group (correlation coefficient 0.75 (P

Abstract In recent years, the development of functional foods targeting gastrointestinal disorders has been in progress. Partially hydrolyzed guar gum (PHGG), which is a water‐soluble dietary fiber, is known to have a constipation‐improving effect. However, many aspects of the mechanism remain unclear. In this study, we investigated the role of aquaporin‐3 (AQP3), which regulates the water content of feces in ameliorative effect of PHGG on constipation. Rats were allowed to freely consume a normal diet or a diet containing 5% PHGG for 14 days, and defecation parameters were measured. We also analyzed the expression levels of genes involved in water transport in the colon. The defecation frequency and volume of rats treated with PHGG were not different from those from the control group, but the fecal water content was significantly increased, and soft stools were observed. The expressions of claudin‐1, tight junction protein‐1, and cadherin‐1, which are involved in tight junctions or adherens junctions, were almost the same in the PHGG‐treated group and the control group. The expression level of AQP3 in the colon was significantly decreased in the PHGG‐treated group. In this study, PHGG decreased the colonic AQP3 expression, thereby suppressing water transport from the luminal side to the vascular side and improving constipation.

Key Clinical Message This case highlights the biomechanical influence of toe amputation on contralateral limb force elevation, possibly through reduced ipsilateral plantar flexor torque production. These findings provide insight into toe amputation‐related compensatory gait mechanics with greater inter‐limb asymmetry, which may increase the risk of musculoskeletal comorbidities, including osteoarthritis in contralateral limb.

Abstract Several cases of autoimmune encephalitis have been reported after ChAdOx1 nCoV‐19 (AZD1222) vaccination. We encountered a male patient who presented with generalized tonic‐clonic seizures, cognitive decline, and gait disturbance that occurred suddenly after the second dose of the ChAdOx1 nCoV‐19 vaccine. Clinical presentation and magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) test results were compatible with limbic encephalitis. Synaptic autoantibody tests confirmed serum and CSF GABA B receptor antibodies were present. The patient was treated with immunotherapy with intravenous immunoglobulin and rituximab. This GABA‐B receptor antibody encephalitis case occurred presumably due to transient autoantibody production following vaccine administration.

Abstract Objective We investigated the longitudinal pattern, determining factors, and clinical implications of brain volume changes in N‐methyl d‐aspartate receptor‐antibody (NMDAR) encephalitis. Methods Baseline clinical profiles, treatment profiles, and outcome measured using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) and modified Rankin scale (mRS) were obtained from a long‐term clinical database documenting an NMDAR encephalitis cohort. In serial MRI, the change in the normalized volume of different brain regions from the baseline evaluation was measured. At each MRI evaluation time point, the cumulative disease burden (CASE score × months) and the cumulative duration of status epilepticus were also evaluated. Results Thirty‐six patients were followed‐up for 28.5 months (range 12–63 months). The volume ratio at last MRI to baseline was the lowest in the cerebellum (94.4 ± 5.7%, p

Abstract Objectives To assess the usefulness of linked color imaging (LCI), a recently developed image‐enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE). Methods Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non‐Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter‐ and intra‐observer agreements were analyzed among endoscopists. Results WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non‐Exs or endoscopists with no experience with EoE patients. Inter‐observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively; p = 0.0013), stricture (kappa, 0.51 vs. 0.39, respectively; p = 0.0072), and diagnosis (kappa, 0.67 vs. 0.57, respectively; p < 0.0001) of EoE. The increase in inter‐observer agreement in WLI+LCI images allowed for a reduction in the differences between the Exs and non‐Ex endoscopists. Intra‐observer agreement for WLI+LCI images surpassed WLIs for a ring (kappa, 0.62 vs. 0.43, p = 0.0052), and a similar trend was found in exudates, furrows, and diagnosis irrespective of the Exs or non‐Exs. Conclusions LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with “moderate” to “substantial” consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.

Abstract Objective Although intravenous immunoglobulin (IVIG) is the first‐line immunotherapy in autoimmune encephalitis, all supporting evidence comes from retrospective case series. Here, we performed a prospective clinical trial of IVIG for functional recovery in autoimmune encephalitis. Methods This single‐arm, open‐label study assessed the efficacy and safety of 10% intravenous IVIG treatment in newly diagnosed patients with possible autoimmune encephalitis. Patients received IVIG (0.4 g/kg/day) for 5 days. Rescue immunotherapy was permitted when the patient deteriorated before day 8 or showed no improvement at day 8. The primary outcome was the change in the modified Rankin Scale (mRS) score at day 8 and 29. The secondary outcomes were the mRS score improvement and the score changes and improvements on four other clinical scales. Results Overall, 23 patients received IVIG (intension‐to‐treat, ITT), and 18 patients completed the study according to the protocol (per‐protocol, PP). mRS improved significantly at days 8 and 29 compared to baseline in both the ITT and PP populations. Other secondary outcomes also improved significantly at day 8, 15, and 29 versus baseline. In the PP population, 6/18 patients achieved favorable outcomes with IVIG alone (mRS = 0~2 at day 8), and 12/18 patients received rescue immunotherapy. Five adverse events were reported in relation to IVIG, all of which were mild. Interpretation IVIG improved neurological functional outcomes, and the improvement was evident by day 8. Adverse effects were tolerable. These data provide the prospective evidence regarding the efficacy of IVIG in improving the functional outcomes of autoimmune encephalitis.

Abstract Aim The aim of this retrospective study was to investigate the incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer. Methods This study involved 2017 patients with stages 0‐III colorectal cancer who underwent laparoscopic surgery at 17 Japanese hospitals between January 2010 and December 2013. We assessed the incidence of postoperative cardiovascular thrombotic and haemorrhagic complications. Results Laparoscopic surgeries were performed in 1152 men and 865 women with 1405 colon and 612 rectal cancers, respectively. Overall, 3%, 38%, 17%, 8%, and 9% of patients had comorbidities of heart failure, high blood pressure, diabetes, history of stroke, and vascular disease, respectively. Antithrombotic agents were being consumed by 17% of patients. The types (and perioperative rest periods) of the antithrombotic agents were aspirin in 58% (18.6 days), clopidogrel in 19% (21.1 days), cilostazol in 13% (13.3 days), and warfarin potassium in 21% (14.6 days) of cases with antithrombotic agents. Surgical time and blood loss in the total cohort were 234 minutes and 56 mL. Four cases (0.2%) had cardiovascular thrombotic complications, including one severe cardiac infarction and one stroke with major sequelae (CHADS2 scores were 2 points in both cases). Hemorrhagic complications occurred in 19 cases (0.9%). In particular, the incidence of the major gastroduodenal haemorrhagic ulcer was higher in cases with antithrombotic agents than without them (0.05% vs 0%, P = .02). Conclusion The incidence of cardiovascular thrombotic complications was rare, although severe cardiac infarction and stroke could occur even after minimally invasive surgery in colorectal cancer.

Thyroid nodules occur in about 60% of the population. A major challenge in thyroid nodule diagnosis is to distinguish between follicular adenoma (FA) and carcinoma (FTC). Here, we present a comprehensive thyroid spectral library covering five types of thyroid tissues. This library includes 121 960 peptides and 9941 protein groups. This spectral library can be used to quantify up to 7863 proteins from thyroid tissues, and can also be used to develop parallel reaction monitoring (PRM) assays for targeted protein quantification. Next, to stratify follicular thyroid tumours, we compared the proteomes of 24 FA and 22 FTC samples, and identified 204 differentially expressed proteins (DEPs). Our data suggest altered ferroptosis pathways in malignant follicular carcinoma. In all, 31 selected proteins effectively distinguished follicular tumours. Of those DEPs, nine proteins were further verified by PRM in an independent cohort of 18 FA and 19 FTC. Together, we present a comprehensive spectral library for DIA and targeted proteomics analysis of thyroid tissue specimens, and identified nine proteins that could potentially distinguish FA and FTC.

Abstract Purpose The aims of this study were to assess the complications associated with the use of an external fixator‐assisted plate osteosynthesis technique to stabilize a femoral bone defect in a rabbit model and to evaluate if this technique could avoid the mispositioning and the displacement of the femoral fragments during the surgical procedure. Methods A preliminary cadaveric animal study was conducted to develop a new technique of external fixator‐assisted plating. Thirty rabbits underwent a surgical procedure consisting in the creation of a femoral bone defect and, subsequently an implantation of a bone substitute through the assistance of a temporary external fixator. The fixator’s ability to maintain length and alignment during surgery was documented. All intraoperative complications were prospectively collected. Results No complications related to the use of the temporary external fixator were reported. The technique successfully prevented mispositioning and dislocation during plating in all the rabbits. Conclusion In a rabbit animal model, the use of an external fixator‐assisted plate osteosynthesis technique appears to be feasible and effective in avoiding misposition and rotation of femoral fragments when performing osteotomy and plating to create a mid‐diaphyseal femoral defect.

Transitions of multistability in materials are exploited for various functions and applications, such as spectral gap tuning, impact energy trapping, and wave steering. However, a fundamental and comprehensive understanding of the transitions, either quasistatic or dynamic transitions, has not yet been acquired, especially in terms of the sequence predictability and tailoring mechanisms. This research, utilizing the stacked Miura‐ori‐variant (SMOV) structure that has multistable shape reconfigurability as a platform, uncovers the deep knowledge of quasistatic and dynamic transitions and proposes the corresponding versatile formation and tuning of mechanical logic gates. Through theoretical, numerical, and experimental means, discriminative and deterministic quasistatic transition sequences, including reversible and irreversible ones, are uncovered, where they constitute a transition map that is editable upon adjusting the design parameters. Via applying dynamic excitations and tailoring the excitation conditions, reversible transitions between all stable configurations become attainable, generating a fully connected transition map. Benefiting from the nonlinearity of the quasistatic and dynamic transitions, basic and compound mechanical logic gates are achieved. The versatility of the scheme is demonstrated using a single SMOV to realize different complex logic operations without increasing structural complexity, showing its unique computing power and inspiring the avenue for efficient physical intelligence.

Abstract Objective Nosocomial bacterial meningitis is one of the major complications after neurosurgery. We performed nanopore 16S amplicon sequencing from cerebrospinal fluid (CSF) to evaluate bacterial meningitis in patients who underwent neurosurgery. Methods Among the patients who visited the neurosurgery department of Seoul National University Hospital between July 2017 and June 2020, those with clinically suspected bacterial meningitis were included. 16S rDNA PCR was performed from the CSF, and nanopore sequencing was performed for up to 3 h. The reads were aligned to the BLAST database. In each case, the culture and the 16S rRNA gene amplicon analysis were simultaneously performed and compared with each other, and we retrospectively reviewed the medical records. Genuine infection was determined by the identical results between conventional culture study and the sequencing, or clinically determined in cases with inconsistent results between the two methods. Results Of the 285 samples obtained from 178 patients who had 16S rDNA PCR, 41 samples (14.4%) were diagnosed with genuine infection. A total of 56.1% (23/41) of the samples with genuine infection showed a false‐negative culture test. In particular, 16S amplicon sequencing was useful in evaluating patients at the initial tests who had infection with intraventricular hemorrhage (Culture false‐negative rate = 100%), subarachnoid hemorrhage (Culture false‐negative rate = 77.8%), and systemic cancer (Culture false‐negative rate = 100%), which are risk factors for central fever. Moreover, 16S amplicon sequencing could suggest the possibility of persistent bacterial meningitis in empirical antibiotic use. Conclusion CSF nanopore 16S sequencing was more effective than conventional CSF culture studies in postoperative bacterial meningitis and may contribute to evidence‐based decisions for antibiotic maintenance and discontinuation.

Abstract Refractory cerebral autoinflammatory–autoimmune diseases are often associated with dysregulated innate immunity and are targeted by anakinra, an interleukin‐1 receptor antagonist. We analyzed the therapeutic effect of anakinra in refractory cerebral autoinflammatory response (CAIR) at a single institution from January 2017 to May 2021. In total, 12 patients with various etiologies were sympathetically treated with anakinra (100 mg/day subcutaneously). Four patients showed good responses, and among these patients, three patients had pathologically demonstrated CAIR. The other eight patients were nonresponsive. No patient had a serious adverse effect. Thus, anakinra may be a therapeutic option for refractory cerebral autoinflammatory diseases.

Abstract Progressive myoclonic epilepsy (PME) is a heterogeneous neurogenetic disorder manifesting as progressive myoclonus, seizure, and ataxia. We report a case of PME caused by a novel DHDDS variant. Additionally, by reviewing the literature on DHDDS mutations, we compared the phenotype of our patient with previously reported phenotypes. We identified DHDDS (c.638G>A, p. Ser213Asn) as a likely pathogenic variant. The literature review revealed 15 PME patients with DHDDS mutations from 13 unrelated families. According to previous studies, late‐onset patients tend to have a slow‐progressive disease course. Although his myoclonus and ataxia were adult onset, our patient experienced rapid disease aggravation.

Abstract Background A reduction in the skeletal muscle mass worsens the prognosis of patients with various cancers. Our previous studies indicated that cisplatin administration to mice caused muscle atrophy. This is a concern for human patients receiving cisplatin. The insulin‐like growth factor 1 (IGF‐1)/phosphoinositide 3‐kinase (PI3K)/Akt pathway stimulates the rate of protein synthesis in skeletal muscle. Thus, IGF‐I can be a central therapeutic target for preventing the loss of skeletal muscle mass in muscle atrophy, although it remains unclear whether pharmacological activation of the IGF‐1/PI3K/Akt pathway attenuates muscle atrophy induced by cisplatin. In this study, we examined whether exogenous recombinant human IGF‐1 attenuated cisplatin‐induced muscle atrophy. Methods Male C57BL/6J mice (8–9 weeks old) were injected with cisplatin or saline for four consecutive days. On Day 5, quadriceps muscles were isolated. Mecasermin (recombinant human IGF‐1) or the vehicle control was subcutaneously administered 30 min prior to cisplatin administration. A dietary restriction group achieving weight loss equivalent to that caused by cisplatin administration was used as a second control. C2C12 myotubes were treated with cisplatin with/without recombinant mouse IGF‐1. The skeletal muscle protein synthesis/degradation pathway was analysed by histological and biochemical methods. Results Cisplatin reduced protein level of IGF‐1 by about 85% compared with the vehicle group and also reduced IGF‐1/PI3K/Akt signalling in skeletal muscle. Under this condition, the protein levels of muscle ring finger protein 1 (MuRF1) and atrophy gene 1 (atrogin‐1) were increased in quadriceps muscles (MuRF1; 3.0 ± 0.1 folds, atrogin‐1; 3.0 ± 0.3 folds, P

Abstract Objective Lamotrigine is one of the most widely used antiepileptic drugs, but it has a critical issue of a skin rash if the starting dose is too high or the escalation rate is too rapid. We investigated the efficacy and safety of a novel and rapid titration protocol for lamotrigine that takes only 11 days to reach a daily dose of 200 mg. Methods We prospectively enrolled 33 adult patients (age 18‐85) who were diagnosed with epilepsy and started lamotrigine administration for the first time at a single tertiary hospital. Our new protocol starts with a subthreshold dose of the drug and then administers a stepwise‐incremental dose until reaching the full therapeutic dose within 11 days. Results Of 29 patients analyzed, only two (6.9%) experienced idiosyncratic skin rash before the first follow‐up visit at 2 weeks (±3 days). In addition, a therapeutic concentration was reached in more than 75% of studied patients after 2 weeks of lamotrigine administration. Significance These findings demonstrate the value of the novel tolerance induction protocol for lamotrigine, which could widen the available application of lamotrigine in various situations. However, this study is a preliminary study limited by a small number of patients and its nonrandomized and open‐label design, so the current protocol needs more rigorous clinical evaluations before the application to the real clinical setting.

Abstract Background Patient and public involvement (PPI) in quality improvement of oncological care pathways for older patients are rare. Objectives Improve the care pathway experience of older cancer patients and explore lessons learned regarding how to engage this vulnerable group. Design Experience‐Based Co‐Design. Setting and participants: Older cancer patients, their caregivers and healthcare professionals within colorectal and breast cancer care pathways. Interventions: Co‐design quality improvement teams. Main outcome measures: Colorectal cancer care pathway touchpoints were (a) availability of a contact person during diagnostic, treatment and aftercare phases; (b) collaboration between physicians and different hospital departments; (c) continuous relationship with same physician; (d) respectful treatment; (e) and information transfer with primary care. Breast cancer care pathway touchpoints were (a) comprehensive information package and information provision, (b) care planning based on patient preferences, (c) continuity of patient–professional relationship and (d) specialized care in case of vulnerability. Challenges related to PPI included (a) ability of older cancer patients to be reflective, critical and think at a collective level; (b) gaining support and commitment of professionals; (d) overcoming cultural differences and power inequalities; and (e) involving researchers and facilitators with appropriate expertise and position. Conclusion This multidisciplinary quality improvement project revealed several challenges of PPI with older cancer patients and their caregivers. Research teams themselves need to assume the role of facilitator to enable meaningful PPI of older cancer patients. Patient or Public Contribution Patient and caregiver representatives and advocates were involved in the design, conduct, analysis, interpretation of the data and preparation of this manuscript.

Abstract Background and Aim Obesity affects the gut microbiome, which in turn increases the risk for colorectal cancer. Several studies have shown the mechanisms by which some bacteria may influence the development of colorectal cancer; however, gut microbiome characteristics in obese patients with colorectal cancer remain unclear. Therefore, this study evaluated their gut microbiome profile and its relationship with metabolic markers. Methods The study assessed fecal samples from 36 consecutive patients with colorectal cancer and 38 controls without colorectal cancer. To identify microbiotic variations between patients with colorectal cancer and controls, as well as between nonobese and obese individuals, 16S rRNA gene amplicon sequencing was performed. Results Principal coordinate analysis showed significant differences in the overall structure of the microbiome among the study groups. The α‐diversity, assessed by the Chao1 index or Shannon index, was higher in patients with colorectal cancer versus controls. The relative abundance of the genera Enterococcus, Capnocytophaga, and Polaribacter was significantly altered in obese patients with colorectal cancer, whose serum low‐density lipoprotein concentrations were positively correlated with the abundance of the genus Enterococcus; among the most abundant species was Enterococcus faecalis, observed at lower levels in obese versus nonobese patients. Conclusions This study demonstrated several compositional alterations of the gut microbiome in patients with colorectal cancer and showed that a reduced presence of E. faecalis may be associated with obesity‐related colorectal cancer development. The gut microbiome may provide novel insights into the potential mechanisms in obesity‐related colorectal carcinogenesis.

Abstract A design technique is developed for the probing signals of a Multi‐Input Multi‐Output (MIMO) radar. The concentration of the energy of the signal in its essential duration and essential bandwidth is achieved through the use of a class of time‐frequency concentrated functions called the WLJ functions as the synthesizing signal set. The goal is to design a signal vector having a pre‐specified desired covariance (CoV) matrix while ensuring that the side‐lobes of the ambiguity functions are small. Since CoV matrices are structurally constrained, they form a manifold in the signal space. Hence, we argue that the difference between these matrices should not be measured in terms of the conventional Euclidean distance (ED); rather, the distance should be measured along the surface of the manifold, that is, in terms of a Riemannian distance (RD). In either case, the signal optimisation problem is non‐convex in the design variables, involving, respectively, a quartic and a square‐root objective function. An efficient algorithm based on successive convex approximation is developed in which the original non‐convex problems are transformed so that they can be approximated by a convex quadratically constrained quadratic problem at each stage, resulting in good approximate solutions. Comparing the designs using ED and RD, we find that the convergence of the algorithm can be significantly faster when optimising over the manifold (RD) than when optimising over the whole space (ED). More importantly, for tight constraints, the use of RD yields solutions which satisfy the constraints far better than the use of ED.

Abstract Plants have evolved sophisticated defense systems to enhance drought tolerance. These include the microRNA (miRNA) group of small noncoding RNAs that act as post‐transcriptional regulators; however, details of the mechanisms by which they confer drought tolerance are not well understood. Here, we show that osa‐MIR171f, a member of osa‐MIR171 gene family, is mainly expressed in response to drought stress and regulates the transcript levels of SCARECROW‐LIKE6‐I (SCL6‐I) and SCL6‐II in rice (Oryza sativa). The SCL6 genes are known to be involved in shoot branching and flag leaf morphology. Osa‐MIR171f‐overexpressing (osa‐MIR171f‐OE) transgenic plants showed reduced drought symptoms compared with non‐transgenic (NT) control plants under both field drought and polyethylene glycol (PEG)‐mediated dehydration stress conditions. Transcriptome analysis of osa‐MIR171f‐OE plants and osa‐mir171f‐knockout (K/O) lines generated by clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) revealed that osa‐mature‐miR171a‐f (osa‐miR171) regulates the expression of flavonoid biosynthesis genes, consequently leading to drought tolerance. This upregulation in the osa‐MIR171f‐OE plants, which did not occur in NT control plants, was observed under both normal and drought conditions. Our findings indicate that osa‐miR171 plays a role in drought tolerance by regulating SCL6‐I and SCL6‐II transcript levels.

This paper aims at the shortcomings of the current conventional processing methods of bearing fault vibration signals in improving signal-to-noise ratio, fine feature extraction, and recognition. A feature extraction and recognition method of abnormal vibration signals based on Ensemble Empirical Mode Decomposition (EEMD) superresolution sparse decomposition is designed. First of all, the superresolution sparse decomposition method is used to refine the set of IMF components of vibration signals after EEMD decomposition. Secondly, the features of the set are extracted and their corresponding energy entropy is calculated. Thirdly, the classification and recognition are carried out. Finally, the effectiveness and feasibility of the method are verified by experiments. It has been proved that this method can better realize the denoising and fine processing aimed at abnormal vibration signals. It has certain theoretical significance and applied value.

Abstract Dexmethylphenidate, and potentially other methylphenidates used in the treatment of attention deficit hyperactivity disorder (ADHD), may cause severe muscle pain and stiffness. Medication side effects should be considered as the possible cause if a patient with ADHD develops severe symptoms.

Abstract Objective The NEK1 gene has been recently implicated in amyotrophic lateral sclerosis (ALS). This study aims to assess the influence of NEK1 variants on the occurrence of ALS and investigate the spectrum and clinical features of NEK1 loss‐of‐function (LOF) variants in a Taiwanese ALS cohort. Methods We screened 325 unrelated ALS patients for coding variants in NEK1 by targeted resequencing and queried the Taiwan Biobank database for NEK1 coding variants in 1000 Taiwanese healthy individuals. The clinical features of the patients with a NEK1 LOF variant were analyzed. Results Six patients and two healthy individuals carried NEK1 LOF variants. The rare missense variants with minor allele frequencies