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A method for the quantitative analysis of molecular species of 1,2-diacylglycerol acetates (1,2-DGAC) containing polyunsaturated fatty acids is described. Phosphatidylethanolamine (PE) isolated from frog retina was used to test the method. PE was converted to 1,2-DGAC by acetolysis. The molecular species of the 1,2-DGAC were resolved by reverse-phase high performance liquid chromatography (HPLC), detected by UV absorption spectroscopy at 210 nm, and identified by gas-liquid chromatography (GLC) of the fatty acid methyl esters (FAME). Molar response curves were generated for each DGAC molecular species that eluted as a single entity from HPLC by determining the moles of fatty acids in the molecular species collected and the response (peak area unit) of the UV detector. Each molecular species response curve was linear from about 10 pmoles to 4-8 nmoles, allowing the slope of each curve to be used as a molar absorptivity. This method provides a means for quantification of most of the molecular species of all glycerolipid classes.

Currently, it is a significant challenge to achieve long-term cyclability and fast chargeability in lithium-ion batteries, especially for the Ni-based oxide cathode, due to severe chemo-mechanical degradation. Despite its importance, the fast charging long-term cycling behaviour is not well understood. Therefore, we comprehensively evaluate the feasibility of fast charging applications for Co-free layered oxide cathodes, with a focus on the extractable capacity and cyclability. The cathodes with a Ni content of over 80% attain 80% of their nominal capacity, along with superior cyclability under fast charging due to the suppression of the following two mechanical failure modes: (i) Li-ion concentration shock fracture (CSF) and (ii) H2-H3 phase shock fracture (HSF). In particular, CSF produces stronger stress than HSF and causes severe crack penetration in mid-Ni cathodes under fast charging. Meanwhile, HSF induces mild internal stress, but prolonged exposure accelerates mechanical degradation. To maximize the fast charging application of high-Ni cathodes, we evaluated a 5C constant current constant voltage protocol to deliver 180 mAh g -1 in 35 min, improving the cycle life by up to 89% over 100 cycles with LiNi 0.90 Mn 0.10 O 2 . This study provides insights into the fast charging applications of high-Ni cathodes, thereby advancing the understanding of their behaviour and optimization.

Diffuse midline gliomas with H3 K27-alteration (DMGH3) are lethal and inoperable brain tumors. Although DMGH3s mainly occur in pediatric patients, they have also occurred in adult patients. This study aimed to analyze the clinicopathological significance of targetable genetic alterations in non-pediatric DMGH3. Next-generation sequencing (NGS) was conducted on 18 non-pediatric DMGH3 patients to analyze additional genetic alterations. The median age at diagnosis was 35 years, and the mean follow-up duration was 762 days. Fourteen cases involved the thalamus-hypothalamus (77.8%). Histologic high-grade features (WHO histologic grade ≥ 3) were observed in 11 (61.1%) patients. H3F3A (H3 K27 M) alterations were identified in all 18 patients using immunohistochemistry and NGS. TP53 mutations were found in 11 patients (61.1%), FGFR1 or PIK3CA in 3 (16.7%), ATRX in 6 (33.3%), NF1 in 4 (22.2%), and KRAS or ATM in 1 (5.6%). TP53 mutations were significantly correlated with high-grade histological features and worse overall survival (OS) (P < 0.05). Despite non-pediatric DMGH3 cases exhibiting superior OS compared to pediatric DMGH3 cases, TP53 mutations were associated with poorer OS outcomes. Notably, FGFR1 and PIK3CA mutations, which have been identified as potential targetable genes, were detected. In conclusion, non-pediatric DMGH3s showed predominant tumor localization within the thalamus and improved prognosis compared to those in pediatric cases, with TP53 alterations correlating with high-grade histology and shorter survival. Genetic profiling, particularly identifying targetable mutations like FGFR1 and PIK3CA, could inform personalized treatment strategies and improve patient outcomes., Competing Interests: Declaration of interests The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Clear cell renal cell carcinoma (ccRCC) often harbors Polybromo 1 (PBRM1) alterations. These alterations are associated with immune checkpoint blockade response in ccRCC, particularly antiprogrammed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1)-targeted therapy. However, the association between PBRM1 alterations and PD-L1 expression in ccRCC remains unclear., Materials and Methods: We analyzed alterations in PBRM1 and PD-L1 expression using immunohistochemistry (IHC) targeting PBRM1 and PD-L1 (22C3) in tissues collected from patients with localized ccRCC (Cohort 1) and advanced ccRCC (Cohort 2). Additionally, next-generation sequencing (NGS) was conducted on Cohort 2 patients to analyze PBRM1 alterations., Results: Cohort 1 comprised 526 patients, of whom 139 (26.4%) exhibited PD-L1 positivity and 205 (38.9%) exhibited loss of PBRM1 expression in IHC. PD-L1 expression was positively associated with the loss of PBRM1 expression (P < 0.001) in localized ccRCC. Kaplan-Meier analysis indicated that PBRM1 expression loss and PD-L1 expression positively correlated with tumor recurrence (P < 0.001 and P = 0.003, respectively). Cohort 2 comprised 59 patients with advanced ccRCC, of whom 33 (56.9%) exhibited PBRM1 genetic alterations. PBRM1 IHC exhibited a sensitivity of 84.48% and specificity of 87.5% compared to NGS results. We did not find a significant association between PBRM1 mutation and PD-L1 expression, in contrast to the findings in Cohort 1. However, we frequently observed that PBRM1 mutation and PD-L1 expression occur concurrently, with 60% of PBRM1-altered ccRCC cases being PD-L1 positive., Conclusion: Although our study did not establish a correlation between PBRM1 mutations and PD-L1 expression, it demonstrated that the occurrence of PBRM1-altered ccRCC with PD-L1 expression is not uncommon. Therefore, the presence of PBRM1 alterations may challenge the use of PD-L1 IHC as a predictive marker for PD-L1 blockade in ccRCC., 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 © 2024 Elsevier Inc. All rights reserved.)

Electrovibration haptic technology, which provides tactile feedback to users by swiping the surface with a finger via electroadhesion, shows promise as a haptic feedback platform for displays owing to its simple structure, ease of integration with existing displays, and simple driving mechanism. However, without electrical grounding on a user's body, the frequent requirement of a high driving voltage near 50 V limits the use of electrovibration haptic technology in practical display applications. This study introduces materials and fabrication strategies that considerably reduce the driving voltage. We used a transparent poly(vinylidene fluoride) (PVDF) thin film deposited on transparent conductive polymers through a simple spin-coating process, thereby enabling easy integration with existing display technologies. The high dielectric constant characteristics of PVDF enabled the production of tactile cues at low voltages (approximately 15 V), which are within the safety limits of common electronics. We verified the feasibility of our electrovibration haptic feedback system on the basis of the absolute threshold voltage through two-alternative forced choice psychological tests. The results revealed that the PVDF dielectric layer exhibited a relatively lower absolute threshold than commonly used polymer films, which possess a relatively lower dielectric constant. To validate the tactile attributes, a Likert five-point scale survey was conducted, considering flat, concave, and convex curvatures. The results indicated that our haptic device can render diverse surface textures, such as "hairy" and "groovy", on the fingertips through the control of applied pulse width modulated voltage signals.

Purpose: This study aimed to investigate the etiology of hearing loss, including genetic variants, in individuals who underwent cochlear implantation (CI) in their teens to thirties. It also sought to analyze post-CI speech performance and identify prognostic factors affecting CI outcomes in this age group., Methods: We conducted a retrospective review of 421 cochlear implant patients at Seoul National University Bundang Hospital, focusing on 63 subjects aged 10-39 years who underwent their first CI by a single surgeon between July 2018 and June 2022. The study included audiologic evaluation, molecular genetic testing, and analysis of speech performance post-CI. Statistical analyses were performed using SPSS 25 and GraphPad Prism 7., Results: Among 63 participants (M:F, 24:39), nine underwent CI in their teens, 24 in their 20 s, and 30 in their 30 s. Most of them (40, 63.5%) had postlingual deafness. The study found that 65.2% (40/63) of subjects received a genetic diagnosis, with DFNB4 being the most common etiology (37.5%, 15/40). Post-CI speech evaluation showed an average sentence score of 80% across all subjects. Factors such as the onset of hearing loss, duration of deafness (DoD), and preoperative Speech Intelligibility Rating (SIR) significantly influenced CI outcomes. Notably, longer DoD was associated with poorer CI outcomes, but this did not affect individuals with postlingual hearing loss as much., Conclusion: The study concludes that in individuals aged 10-39 undergoing CI, the onset of hearing loss and preoperative SIR are critical predictors of postoperative outcomes. CI is recommended for those with postlingual hearing loss in this age group, irrespective of the DoD. The study highlights the importance of genetic factors especially DFNB4 in hearing loss etiology and underscores the value of the relatively easy-to-evaluate factor, preoperative SIR in predicting CI outcomes., (© 2024. The Author(s).)

Rationale: Acute injury to the sacroiliac joint (SIJ) can result from high-energy external forces that cause a combination of axial loading and sudden rotational movements, resulting in severe pain that cannot be relieved by regular nonsteroidal anti-inflammatory drugs. The treatment includes injections of steroids and local anesthetics to reduce pain and promote healing. Here, we report the case of a patient with acute sacroiliac pain who did not respond to conventional injection therapy., Patient Concerns: A 58-year-old male patient who did not exercise regularly experienced pain in his left groin and difficulty walking while kicking on his right leg. He received two injections and manual therapy at a local orthopedic clinic; however, his symptoms did not improve despite taking painkillers., Diagnoses: Radiographic images showed no abnormalities. After confirming the cause of onset, pain pattern, physical examination, and tenderness, the patient was diagnosed with an acute SIJ sprain (static blood)., Interventions: At the first visit, a single acupotomy was performed on the seven treatment points identified during the physical examination, and immediate improvement in symptoms was confirmed. From then on, Korean medicine (KM) treatments, such as acupuncture, cupping, chuna, and bee venom pharmacopuncture, were performed., Outcomes: Immediately after acupotomy, groin pain improved by 80 %, gait immediately normalized, and the patient showed no symptoms at the 9th visit., Lessons: For SIJ-type groin pain that does not respond to existing treatments, immediate relief is achieved after a single acupotomy at the exact treatment point. Therefore, in the future, the importance of identifying a precise treatment point for SIJ pain should be recognized, and the use of Korean medicine treatment techniques, including acupotomy, should be considered., (Copyright © 2024. Published by Elsevier Inc.)

Nerve guidance conduits (NGCs) are widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue-mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel-based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, a novel double-network (DN) hydrogel using alginate and gelatin by a two-step crosslinking process involving chemical-free gamma irradiation and ionic crosslinking, is developed. DN hydrogels (1% alginate and 15% gelatin), crosslinked with 30 kGy gamma irradiation and barium ions, exhibit substantially improved mechanical properties, including tensile strength, elastic modulus, and fracture stain, compared to single network (SN) gelatin hydrogels. Additionally, the DN hydrogel NGC exhibits excellent kink resistance, mechanical stability to successive compression, suture retention, and enzymatic degradability. In vivo studies with a sciatic defect rat model indicate substantially improved nerve function recovery with the DN hydrogel NGC compared to SN gelatin and commercial silicone NGCs, as confirm footprint analysis, electromyography, and muscle weight measurement. Histological examination reveals that, in the DN NGC group, the expression of Schwann cell and neuronal markers, myelin sheath, and exon diameter are superior to the other controls. Furthermore, the DN NGC group demonstrates increased muscle fiber formation and reduced fibrotic scarring. These findings suggest that the mechanically robust, degradable, and biocompatible DN hydrogel NGC can serve as a novel platform for peripheral nerve regeneration and other biomedical applications, such as implantable tissue constructs., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Aims: Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have shown promising clinical outcomes in urothelial carcinoma (UC). The combined positive score (CPS) quantifies PD-L1 22C3 expression in UC, but it can vary between pathologists due to the consideration of both immune and tumour cell positivity., Methods and Results: An artificial intelligence (AI)-powered PD-L1 CPS analyser was developed using 1,275,907 cells and 6175.42 mm 2 of tissue annotated by pathologists, extracted from 400 PD-L1 22C3-stained whole slide images of UC. We validated the AI model on 543 UC PD-L1 22C3 cases collected from three institutions. There were 446 cases (82.1%) where the CPS results (CPS ≥10 or <10) were in complete agreement between three pathologists, and 486 cases (89.5%) where the AI-powered CPS results matched the consensus of two or more pathologists. In the pathologist's assessment of the CPS, statistically significant differences were noted depending on the source hospital (P = 0.003). Three pathologists reevaluated discrepancy cases with AI-powered CPS results. After using the AI as a guide and revising, the complete agreement increased to 93.9%. The AI model contributed to improving the concordance between pathologists across various factors including hospital, specimen type, pathologic T stage, histologic subtypes, and dominant PD-L1-positive cell type. In the revised results, the evaluation discordance among slides from different hospitals was mitigated., Conclusion: This study suggests that AI models can help pathologists to reduce discrepancies between pathologists in quantifying immunohistochemistry including PD-L1 22C3 CPS, especially when evaluating data from different institutions, such as in a telepathology setting., (© 2024 John Wiley & Sons Ltd.)

Background: This study compared hearing outcomes with use of personal sound amplification products (PSAPs) and hearing aids (HAs) in patients with moderate to moderately severe unilateral hearing loss., Methods: Thirty-nine participants were prospectively enrolled, and randomly assigned to use either one HA (basic or premium type) or one PSAP (basic or high-end type) for the first 8 weeks and then the other device for the following 8 weeks. Participants underwent a battery of examinations at three visits, including sound-field audiometry, word recognition score (WRS), speech perception in quiet and in noise, real-ear measurement, and self-report questionnaires., Results: Functional gain was significantly higher with HAs across all frequencies ( P < 0.001). While both PSAPs and HAs improved WRS from the unaided condition, HAs were superior to PSAPs. The speech recognition threshold in quiet conditions and signal-to-noise ratio in noisy conditions were significantly lower in the HA-aided condition than in the PSAP-aided condition, and in the PSAP-aided condition than in the unaided condition. Subjective satisfaction also favored HAs than PSAPs in questionnaires, Abbreviated Profile of Hearing Aid Benefit, International Outcome Inventory for Hearing Aids, and Host Institutional Questionnaire., Conclusion: While PSAPs provide some benefit for moderate to moderately severe unilateral hearing loss, HAs are more effective. This underscores the potential role of PSAPs as an accessible, affordable first-line intervention in hearing rehabilitation, particularly for individuals facing challenges in accessing conventional HAs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Despite progress in multiparametric magnetic resonance imaging (MRI), issues of prostate cancer invisibility and underestimated tumor burden persist. This study investigates the potential of an ultra-high field MRI at 7-T in an ex-vivo setting to address these limitations., Methods: This prospective study included 54 tumors from 20 treatment-naïve clinically significant prostate cancer patients, confirmed by biopsy, despite negative findings on preoperative 3-T MRI. Ex-vivo 7-T MRI of resected prostates was performed, with assessment on tumor visibility and size. Factors influencing visibility were analyzed using logistic regression analyses., Results: Tumor visibility was confirmed in 80% of patients, and 48% of all tumors on ex-vivo imaging. Gleason pattern 4 percentage (odds ratio 1.09) and tumor size on pathology (odds ratio 1.36) were significantly associated with visibility ( P  < 0.05). Mean MRI-visible and invisible tumor sizes were 10.5 mm and 5.3 mm, respectively. The size discrepancy between MRI and pathology was 2.7 mm., Conclusion: Tumor visibility on ex-vivo 7-T MRI was influenced by tumor grade and size. The notable tumor visibility initially overlooked on 3-T MRI, along with small size discrepancy with pathology, suggests potential improvements in resolution., (© 2024 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics 1-7 . However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains 8-15 . Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN., (© 2024. The Author(s).)

This study aimed to compare the development of pronunciation in South Korean preschoolers with unilateral cochlear nerve deficiency (CND) to that of age-matched preschoolers with normal hearing, a topic that has not been explored previously. In a retrospective analysis, 25 preschoolers with unilateral CND who had undergone a speech evaluation battery, including a pronunciation and vocabulary test, were enrolled. Utilizing the Urimal Test of Articulation and Phonation and customized language ability tests, pronunciation and vocabulary were assessed. The subjects' speech evaluation scores were converted into age-adjusted z-scores using normal controls' data. While vocabulary performance was within normal limits, their average pronunciation z-score was -2.90, significantly lower than both the zero reference point and their vocabulary z-scores. None of the subjects scored above average in pronunciation. Thirteen patients were recommended for articulation therapy, seven were considered as potential candidates for this therapy, and the remaining five were within normal limits. There was no observed correlation between the development of pronunciation and vocabulary. Notably, some subjects' pronunciation scores did not improve, even after serial follow-up during their preschool years. Despite typical vocabulary development, preschoolers with unilateral CND exhibit significant delays in pronunciation. These findings emphasize the necessity for vigilant monitoring of their language development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choe 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.)

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy 3 2+ ) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

Recently, the cost of lithium-ion batteries has risen as the price of lithium raw materials has soared and fluctuated. Notably, the highest cost of lithium production comes from the impurity elimination process to satisfy the battery-grade purity of over 99.5%. Consequently, re-evaluating the impact of purity becomes imperative for affordable lithium-ion batteries. In this study, we unveil that a 1% Mg impurity in the lithium precursor proves beneficial for both the lithium production process and the electrochemical performance of resulting cathodes. This is attributed to the increased nucleation seeds and unexpected site-selective doping effects. Moreover, when extended to an industrial scale, low-grade lithium is found to reduce production costs and CO 2 emissions by up to 19.4% and 9.0%, respectively. This work offers valuable insights into the genuine sustainability of lithium-ion batteries., (© 2024. The Author(s).)

Radio frequency (RF) electronics are vital components of stretchable electronics that require wireless capabilities, ranging from skin-interfaced wearable systems to implantable devices to soft robotics. One of the key challenges in stretchable electronics is achieving near-lossless transmission line technology that can carry high-frequency electrical signals between various RF components. Almost all existing stretchable interconnection strategies only demonstrate direct current or low-frequency electrical properties, limiting their use in high frequencies, especially in the MHz to GHz range. Here, we describe the design and fabrication of a simple stretchable RF transmission line strategy that integrates a quasi-microstrip structure into a stretchable serpentine microscale interconnection. We show the effects of quasi-microstrip structural dimensions on the RF performance based on detailed quantitative analysis and experimentally demonstrate the optimized device capable of carrying RF signals with frequencies of up to 40 GHz with near-lossless characteristics. To show the potential application of our transmission line in stretchable microwave electronics, we designed a single-stage power amplifier system with a gain of 9.8 dB at 9 GHz that fully utilizes our quasi-microstrip transmission line technology.

Background: Limited evidence exists assessing whether anastomotic evaluation using indocyanine green fluorescence (IGF) during minimally invasive esophagectomy (MIE) predicts or improves outcomes. We hypothesized that IGF helps surgeons predict anastomotic complications and reduces anastomotic leaks after MIE., Methods: In September 2019, our institution began routinely using IGF for intraoperative evaluation of anastomoses during MIE. Data were collected from patients undergoing MIE in the two years before and after this technology began being routinely used. Baseline characteristics and outcomes, including anastomotic leak, in patients who underwent indocyanine green fluorescence evaluation (ICG) and those who did not (nICG) were compared. Outcomes were also compared between ICG patients with normal versus abnormal fluorescence., Results: Overall, 181 patients were included. Baseline demographic and clinical characteristics did not differ between the ICG and nICG groups. ICG patients experienced higher rates of anastomotic leak (10.2% vs. 1.6%, P = .015) and 90-day mortality (8.5% vs. 1.6%, P = .04) compared to nICG patients. Due to lack of equipment availability, 19 nICG patients underwent MIE after the use of IGF became routine, and none developed leaks. ICG patients with abnormal fluorescence had higher rates of anastomotic leak (71.4% vs 1.9%, P < .001) and 30-day mortality (28.6% vs 0%, P = .012) compared to those with normal fluorescence., Discussion: Abnormal intraoperative IGF was associated with increased rate of anastomotic leak, suggesting predictive potential of IGF. However, its use was associated with an increased leak rate and higher mortality. Further studies are warranted to assess possible physiologic effects of indocyanine green on the esophageal anastomosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To evaluate the diagnostic performance of the tumor contact length (TCL) in the prediction of MIBC (muscle-invasive bladder cancer) in lesions corresponding to the vesical imaging-reporting and data system (VIRADS) score 2-3., Methods: This is a single institution, retrospective study targeting 191 consecutive patients assigned of VIRADS score 2-3, who had pre-transurethral resection MRI from July 2019 to September 2021. Logistic regression analyses were performed to determine meaningful predictors of MIBC for this score group, and a nomogram was plotted with those variables. The diagnostic performance of each predictor was compared at predefined thresholds (VIRADS score 3 and TCL 3 cm) using the generalized linear model and ROC analysis., Results: Both VIRADS score and TCL remained independent predictors of MIBC for this score group (odds ratio 7.3 for VIRADS score, and 1.3 for TCL, p < 0.01 for both). The contribution of TCL to the probability of MIBC in the nomogram was greater than that of the VIRADS score. VIRADS score had a sensitivity of 0.54 (14/26), specificity of 0.92 (203/221), and diagnostic accuracy of 0.88 (217/247), and TCL showed a sensitivity of 0.89 (23/26), specificity of 0.95 (209/221), and diagnostic accuracy of 0.94 (232/247). The difference in sensitivity (p = 0.03) and accuracy (p = 0.04) was statistically significant. The AUC was also significantly wider for TCL than for VIRADS (0.97 vs. 0.73, p < 0.01)., Conclusion: A simple index, TCL, may be helpful in further risk stratification for MIBC in patients with a score of VIRADS 2-3., Clinical Relevance Statement: For bladder cancer patients with insufficient qualitative evidence of muscle layer invasion using VIRADS categorization, TCL, a simple quantitative indicator defined as the curvilinear contact length between the bladder wall and the tumor, may be helpful in risk stratification., Key Points: • Even when only lesions with score 2-3 were targeted, VIRADS was still a meaningful indicator of MIBC. • With a predefined threshold of 3 cm applied, TCL outperformed VIRADS in the score 2-3 group, in predicting MIBC. • A longer TCL for a lesion with a VIRADS score 2 may warrant an additional warning for MIBC, whereas a shorter TCL for a lesion with a score 3 may indicate a lower risk of MIBC., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Ewing sarcoma and peripheral primitive neuroectodermal tumor (ES/pPNET) is an undifferentiated malignant tumor that is most prevalent in children and young adults and often radiologically mimics a meningioma. A 38-year-old female patient visited our hospital with complaints of right-sided tinnitus, right hemiparesis, and imbalance. She underwent preoperative imaging and was subsequently diagnosed as having a meningioma on the petrous ridge. After partial resection, EWSR1-FLI1 gene fusion was confirmed, and she was diagnosed with ES/pPNET. The tumor was successfully treated using a multidisciplinary approach of adjuvant chemo- and radiotherapy. This case is noteworthy because it is an extremely rare case of an intracranial ES/pPNET, and it is worth sharing our clinical experience that the tumor was successfully treated through a multidisciplinary therapeutic approach even though complete resection was not achieved., Competing Interests: Chae-Yong Kim, a contributing editor of Brain Tumor Research and Treatment, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics., 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. Published by Elsevier B.V.)

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH -wildtype secondary glioblastoma arising in IDH -mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH -mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH -1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH -wildtype secondary glioblastoma arising in IDH -mutant diffuse astrocytoma.

Hearing in neonates and infants is crucial for their development of language and communication skills. Unless hearing loss is appropriately managed early, it can cause a significant socioeconomic burden considering its detrimental impact on the child's development and its common nature. It is also the most common congenital sensory deficit, with an approximate incidence of 1.5 per 1,000 newborns. Its etiologies are heterogeneous: genetic causes are reportedly involved in up to 80% of cases, while congenital cytomegalovirus infection is the leading environmental factor contributing to congenital hearing loss. The introduction of newborn hearing screening using automated auditory brainstem response and/or automated otoacoustic emission in many developed countries has helped detect and manage hearing loss early. Current auditory rehabilitation options such as cochlear implantation implementing cutting-edge technologies can treat almost all degrees of hearing loss, emphasizing the importance of early hearing detection and intervention. Rapidly developing genetic diagnostic technologies and future cutting-edge treatment options, including gene therapy, will shed light on the future management of hearing loss in neonates and infants.

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jae Young Lee reports financial support was provided by 10.13039/501100003725National Research Foundation of Korea., (© 2023 The Authors.)

Background: The cochlea contains a robust biological clock associated with auditory function, exhibiting diurnal sensitivity to noise or ototoxicity., Objectives: We examined the relationship between disrupted circadian rhythm and altered expression of circadian clock genes in patients with sudden sensorineural hearing loss (SSNHL) and explored whether the circadian clock genes serve as prognostic biomarkers., Material and Methods: Twelve patients with SSNHL were enrolled study group. Twelve people with normal hearing were enrolled voluntarily for comparison. Audiological evaluation was performed to evaluate hearing thresholds. Korean version of the Pittsburgh Sleep Quality Index Questionnaire was performed to evaluate sleep quality and patterns. Circadian clock genes including for PERI , PER2 , PER3 , CRYI , CRY2 , CLOCK , ARNTL , CSNKIE , and TIMELESS expression in blood were evaluated using real-time quantitative PCR method., Results: Compared with healthy controls without hearing loss, most of the circadian clock genes were markedly downregulated, coupled with low sleep quality and disturbing patterns, in patients with SSNHL. Intriguingly, a weak correlation between hearing improvement following steroid treatment and altered levels of circadian clock genes was observed., Conclusions and Significance: This study provides an additional basis for the relevance of disrupted circadian rhythm to SSNHL and suggests a possible prognostic biomarker for SSNHL treatment.

Myocardial infarction (MI) is a major cause of death worldwide. After the occurrence of MI, the heart frequently undergoes serious pathological remodeling, leading to excessive dilation, electrical disconnection between cardiac cells, and fatal functional damage. Hence, extensive efforts have been made to suppress pathological remodeling and promote the repair of the infarcted heart. In this study, we developed a hydrogel cardiac patch that can provide mechanical support, electrical conduction, and tissue adhesiveness to aid in the recovery of an infarcted heart function. Specifically, we developed a conductive and adhesive hydrogel (CAH) by combining the two-dimensional titanium carbide (Ti 3 C 2 T x ) MXene with natural biocompatible polymers [i.e., gelatin and dextran aldehyde (dex-ald)]. The CAH was formed within 250 s of mixing the precursor solution and could be painted. The hydrogel containing 3.0 mg/mL MXene, 10% gelatin, and 5% dex-ald exhibited appropriate material characteristics for cardiac patch applications, including a uniform distribution of MXene, a high electrical conductivity (18.3 mS/cm), cardiac tissue-like elasticity (30.4 kPa), strong tissue adhesion (6.8 kPa), and resistance to various mechanical deformations. The CAH was cytocompatible and induced cardiomyocyte (CM) maturation in vitro, as indicated by the upregulation of connexin 43 expression and a faster beating rate. Furthermore, CAH could be painted onto the heart tissue and remained stably adhered to the beating epicardium. In vivo animal studies revealed that CAH cardiac patch treatment significantly improved cardiac function and alleviated the pathological remodeling of an infarcted heart. Thus, we believe that our MXene-based CAH can potentially serve as a promising platform for the effective repair of various electroactive tissues including the heart, muscle, and nerve tissues.

This study reports on diffuse leptomeningeal glioneuronal tumor (DL-GNT) in a 29-year-old male. DL-GNT is a rare central nervous system (CNS) tumor mostly seen in children and only few cases have been reported in adult patients. Our patient presented with a chronic headache that lasted for five months. MR imaging showed mild hydrocephalus, multiple rim-enhancing nodular lesions in the suprasellar cistern, diffuse leptomeningeal enhancement in the lumbosacral area, and multiple small non-enhancing cyst-appearing lesions not suppressed on fluid attenuated inversion recovery (FLAIR) images in the bilateral basal ganglia, thalami, and cerebral hemispheres. Under the impression of germ cell tumor with leptomeningeal seeding, the patient underwent trans-sphenoidal tumor removal. DL-GNT was pathologically confirmed and FGFR1 mutation was detected through a next-generation sequencing test. In conclusion, a combination of leptomeningeal enhancement and multiple parenchymal non-enhancing cyst-appearing lesions not suppressed on FLAIR images may be helpful for differential diagnosis despite overlapping imaging features with many other CNS diseases that have leptomeningeal enhancement., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2023 The Korean Society of Radiology.)

This study aimed to investigate the effect of electrical stimulation on poly(d,l-lactide- co -ε-caprolactone) nerve guidance conduits (NGCs) in promoting the recovery of facial function and nerve regeneration after facial nerve (FN) injury in a rat model. In the experimental group, both the NGC and transcutaneous electrical nerve stimulation (ES) were used simultaneously; in the control group, only NGC was used. ES groups were divided into two groups, and direct current (DC) and charge-balanced pulse stimulation (Pulse) were applied. The ES groups showed significantly improved whisker movement than the NGC-only group. The number of myelinated neurons was higher in ES groups, and the myelin sheath was also thicker and more uniform. In addition, the expression of neurostructural proteins was also higher in ES groups than in the NGC-only group. This study revealed that FN regeneration and functional recovery occurred more efficiently when ES was applied in combination with NGCs.

Purpose: To evaluate the diagnostic performance of follow-up multiparametric MRI for prediction of recurrent prostate cancer after high-intensity focused ultrasound (HIFU), and to find other, if any, clinical or radiological predictors., Materials and Methods: Post-HIFU MRIs of 110 consecutive patients who underwent follow-up biopsies between August 2019 and April 2021 were retrospectively analyzed and the likelihood of recurrence was assessed on a five-point Likert scale by two board-certified uroradiologists. Diagnostic performance of the Likert scale assigned to the post-HIFU MRI was assessed using the follow-up biopsy results as a reference standard. Among the clinical and radiological variables, predictors of the recurrence were examined through logistic regression., Results: In per-patient and per-sector analyses, Likert scale on post-HIFU MRI showed a sensitivity and specificity of 0.37 and 0.97, and 0.42 and 0.87, respectively, in predicting recurrence. Two patients with high suspicion on MRI required additional treatment to regain biochemical control despite negative biopsies. High suspicion on post-HIFU MRI (odds ratio = 1.74; p < 0.01), and more cancer-positive cores on initial biopsy (odds ratio = 1.25; p = 0.03) were independent predictors of recurrence., Conclusion: Albeit with low sensitivity, high suspicion on post-HIFU MRI may be clinically important because of its high specificity, especially when considering the possibility of sampling error in biopsies. Patients with a high number of cancer-positive cores at diagnosis should avoid HIFU as they have an increased risk of recurrence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Self-assembled peptide (SAP)-substance P (SP) hydrogels can be retained in the joint cavity longer than SP alone, and they can alleviate inflammation and ameliorate cartilage regeneration in knee osteoarthritis (OA). We conducted a preclinical study using diverse animal models of OA and an in vitro study using human synoviocytes and patient-derived synovial fluids to demonstrate the effect of SAP-SP complex on the inflammation and cartilage regeneration., Methods: Surgical induction OA model was prepared with New Zealand white female rabbits and chemical induction, and naturally occurring OA models were prepared using Dunkin Hartely female guinea pigs. The SAP-SP complex or control (SAP, SP, or saline) was injected into the joint cavities in each model. We performed micro-computed tomography (Micro-CT) analysis, histological evaluation, immunofluorescent analysis, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) assay and analyzed the recruitment of intrinsic mesenchymal stem cells (MSCs), macrophage activity, and inflammatory cytokine in each OA model. Human synoviocytes were cultured in synovial fluid extracted from human OA knee joints injected with SAP-SP complexes or other controls. Proliferative capacity and inflammatory cytokine levels were analyzed., Results: Alleviation of inflammation, inhibition of apoptosis, and enhancement of intrinsic MSCs have been established in the SAP-SP group in diverse animal models. Furthermore, the inflammatory effects on human samples were examined in synoviocytes and synovial fluid from patients with OA. In this study, we observed that SAP-SP showed anti-inflammatory action in OA conditions and increased cartilage regeneration by recruiting intrinsic MSCs, inhibiting progression of OA., Conclusions: These therapeutic effects have been validated in diverse OA models, including rabbits, Dunkin Hartley guinea pigs, and human synoviocytes. Therefore, we propose that SAP-SP may be an effective injectable therapeutic agent for treating OA. In this manuscript, we report a preclinical study of novel self-assembled peptide (SAP)-substance P (SP) hydrogels with diverse animal models and human synoviocytes and it displays anti-inflammatory effects, apoptosis inhibition, intrinsic mesenchymal stem cells recruitments and cartilage regeneration., (© 2023. The Author(s).)

Children with cleft palate are susceptible to otitis media with effusion. This study aimed to investigate the effect of lateral relaxing incision (RI) on middle ear function in cleft palate patients who underwent palatoplasty using double-opposing Z-plasty (DOZ). This is a retrospective study of patients who underwent bilateral ventilation tube insertion concurrently with DOZ, wherein RI was selectively performed on the right side of the palate (Rt-RI group) or not (No-RI group). The frequency of VTI, duration of the first ventilation tube retention, and hearing outcomes at the last follow-up were reviewed. Outcomes were compared using the χ 2 test and t test. A total of 126 treated ears from 63 non-syndromic children (18 male, 45 female) with cleft palate were reviewed. The mean age at surgery was 15.8±6.17 months. There were no significant differences in the frequency of ventilation tube insertion between the right and left ears within the Rt-RI group or between the Rt-RI and no-RI groups in the right ear. Subgroup analysis for ventilation tube retention time, auditory brainstem response thresholds, and air-conduction pure tone averages showed no significant differences. In the DOZ, the use of RI had no significant effects on middle ear outcomes during 3 years of follow-up. Relaxing incision seems to be safe without concern for middle ear function in children with cleft palate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Purpose: To examine the subjective and objective audiological benefits of the Osia system compared to devices commonly implanted prior to the introduction of this system., Methods: Osia recipients with either conductive hearing loss (CHL/MHL) (n = 9) or single-sided deafness (SSD) (n = 8) who underwent surgery from February 2021 to March 2022 were prospectively recruited. The audiological outcomes and usage rate of Osia implantees were compared with those of retrospectively recruited patients implanted with other devices (n = 50). The subjective satisfaction of the Osia implantees was also evaluated through questionnaires., Results: All users of the Osia system were classified as regular users. In the CHL/MHL group, the effective gain of the Osia system (11.1 ± 14.9 dB) surpassed that of the Baha and Bonebridge (- 2.7 ± 12.6 dB) at 2 kHz (p = 0.01, Mann-Whitney U test). Among the devices, the Osia system tended to tolerate the worst bone conduction thresholds, up to the level of 61 dB. In the SSD group, the functional gain of Osia at 4 kHz (37.5 ± 3.1 dB) was higher than that of the Baha and Bonebridge group (26.9 ± 3.0 dB) (p = 0.05, Mann-Whitney U test)., Conclusion: The Osia system yielded larger audiological gain than the Baha Attract and Bonebridge devices, especially at high frequencies, leading to substantially higher compliance. The Osia system tended to have the strongest tolerance to aggravated bone conduction thresholds among the available transcutaneous bone conduction hearing implants. Therefore, the Osia system could potentially be a good option for CHL/MHL patients with bone conduction thresholds of 50 dB HL or more, as well as patients with SSD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is substantially challenging for transition metal oxide nanoparticle (NP)-based electrodes for supercapacitors to achieve high transparency and large capacity simultaneously due to the inherent trade-off between optical transmittance (T) and areal capacitance (C A ). This study demonstrates how this trade-off limitation can be overcome by replacing some electrode NPs with transparent tin oxide (SnO 2 ) NPs. Although SnO 2 NPs are non-capacitive, they provide effective paths for charge transport, which simultaneously increase the C A and T 550nm of the manganese oxide (Mn 3 O 4 ) NP electrode from 11.7 to 13.4 mF cm -2 and 82.1% to 87.4%, respectively, when 25 wt% of Mn 3 O 4 are replaced by SnO 2 . The obtained C A values at a given T are higher than those of the transparent electrodes previously reported. An energy storage window fabricated using the mixed-NP electrodes exhibits the highest energy density among transparent supercapacitors previously reported. The improved energy density enables the window to operate various electronic devices for a considerable amount of time, demonstrating its applicability in constructing a reliable and space-efficient building-integrated power supply system., (© 2023 Wiley-VCH GmbH.)

In this study, the deformation of concrete materials was evaluated using a mechanochromic sensor that detects the discoloration reaction caused by deformation. This sensor was attached by applying the Loctite adhesive to both ends in the longitudinal direction. The process of applying tensile stress to the specimens was videotaped, and the deformation and discoloration were examined through image analysis. The mechanochromic sensor was not affected by the finished surface condition, and the discoloration reaction was detected for a concrete material deformation level of up to 0.01 mm. The detected level was caused by the elongation of the sensor, and the discoloration compared with the initial color was identified. In addition, the integration behavior of the mechanochromic sensor under the deterioration of concrete members in cold areas and winter environments, as well as the discoloration reaction of the sensor in a low-temperature environment, was examined. It was found that the discoloration ability of the mechanochromic sensor exposed to a low-temperature environment was restored in 2 h after the end of the freeze-thaw test, and it was judged that the deformation and discoloration levels will be properly measured when the surface temperature of the sensor is restored to a room temperature of approximately 15 °C. This appeared to be due to the room temperature recovery of the dielectric spacer of the sensor and the deformation structure of the resonance condition. The sensor was also attached when diagonal cracks occurred in the concrete beam members to evaluate the strain and discoloration rate according to the deformation and discoloration levels. Accordingly, the cracks and deformation of the concrete materials were monitored using measured values from the discoloration of the mechanochromic sensors, and the possibility of measuring the crack width was reviewed only by real-time monitoring and imaging with the naked eye.

Background and Purpose: We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction., Materials and Methods: A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients' MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the 'FastSurfer' platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction., Results: The median age was 50 years (range, 16-86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54-60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = -0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = -6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced., Conclusions: GM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic caused a shift from in-person care to telemedicine, providing a unique opportunity to evaluate trends and efficiency of telemedicine usage within surgical subspecialties in a large, integrated health care system before and after shelter in place mandates., Methods: This retrospective cohort study included all of the Kaiser Permanente Northern California members referred to surgical services from January 1, 2019 to June 13, 2020 and receiving a surgical procedure. We compared the patient referrals (categorized as benign, urgent, or cancer) before and after shelter in place mandates, and we examined rates of telemedicine (video or telephone) usage for preoperative consultations, postoperative visits, time from referral to first surgical encounter, and to surgery or procedure. In multivariate analyses, we assessed the patient and provider characteristics associated with telemedicine usage., Results: There was a total of 34,875 surgical referrals resulting in a procedure, with a significant decline in referral after shelter in place mandates. Preoperative encounter types shifted from 89.8% in-person before shelter in place mandates to 70.2% telemedicine after shelter in place mandates (P &lt; .0001). The median time from referral to first encounter decreased after shelter in place mandates, as did median time to procedure. After shelter in place mandates, postoperative encounters were mainly telemedicine (65.8%) compared with before shelter in place mandates (41.7%) (P &lt; .0001). Overall, there was a comparable uptake of telemedicine usage in almost all evaluated categories of patient characteristics after shelter in place mandates., Conclusion: Within a health care system with prior telemedicine capability, surgical specialties were able to shift to telemedicine rapidly, equitably, and efficiently in the preoperative and postoperative encounters of benign, urgent, and cancer diagnosis during mandated COVID-19 restrictions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: Many otologists face a dilemma in the decision-making process of surgical management of patients with cochlear nerve (CN) aplasia. The goal of this study is to provide fresh evidence on cochlear implantation (CI) results in patients with CN aplasia. Materials and Methods: We scrutinized functional outcomes in 37 ears of 21 children with bilateral CN aplasia who underwent unilateral or bilateral CI based on cross-sectional and longitudinal assessments. Results: The Categories of Auditory Performance (CAP) scores gradually improved throughout the 3-year follow-up; however, variable outcomes existed between individuals. Specifically, 90% of recipients with a 1-year postoperative CAP score ≤1 could not achieve a CAP score over 1 even at 3-year postoperative evaluation, while the recipients with a 1-year postoperative CAP score >1 had improved auditory performance, and 72.7% of them were able to achieve a CAP score of 4 or higher. Meanwhile, intraoperative electrically evoked compound action potential was not correlated with postoperative CAP score. Conclusions: Our results further refine previous studies on the clinical feasibility of CI as the first treatment modality to elicit favorable auditory performance in children with CN aplasia. However, special attention should be paid to pediatric patients with an early postoperative CAP score ≤1 for identification of unsuccessful cochlear implants and switching to auditory brainstem implants.

Background: Grade 2/3 meningiomas have locally aggressive behaviors often requiring additional treatment plans after surgical resection. Herein, we explored the clinical significance of next-generation sequencing (NGS) in characterizing the molecular profiles of high-grade meningiomas., Methods: Patients with intracranial meningioma who underwent surgical resection in a single institution were retrospectively reviewed. Clinicopathologic relevance was evaluated using recurrence-free survival (RFS) as an outcome measure. NGS for the targeted gene regions was performed in 40 participants., Results: Among the 713 individuals in the study population, 143 cases (20.1%) were identified as having grade 2 or 3 meningiomas with a significantly lower female predominance. While the difference in RFS between grade 2 and 3 meningiomas was insignificant, a few conventional grade 2 cases, but with TERT promoter hotspot mutation, were highly progressive and refractory to the treatment. From the NGS study, recurrent mutations in TRAF and AKT1 were identified with a higher prevalence (17.5% and 12.5%, respectively) compared with grade 2/3 meningiomas reported in previous literature. However, their relations to other histopathologic properties or clinical factors were rarely observed., Conclusions: Grade 2/3 meningiomas show a broad spectrum of molecular profiles, as they have heterogeneous histologic characteristics., 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 Kim, Hwang, Kwon, Lee, Lee, Choe, Han and Kim.)

Hydrogels mimicking the physicochemical properties of the native extracellular matrix have attracted great attention as bioinks for three-dimensional (3D) bioprinting in tissue engineering applications. Alginate is a widely used bioink with beneficial properties of fast gelation and biocompatibility; however, bioprinting using alginate-based bioinks has several limitations, such as poor printability, structural instability, and limited biological activities. To address these issues, we formulated various bioinks using bone morphogenetic protein-2 (BMP-2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and alginate for mesenchymal stem cell (MSC) printing and induction of osteogenic differentiation. Incorporation of PLGA nanoparticles into alginate could enhance the mechanical properties and printability of the bioink. In particular, Alg/NP N 30 (30 mg/mL PLGA nanoparticles and 3% w/v alginate) was most suitable for 3D printing with respect to printability and stability. BMP-2-loaded PLGA nanoparticles (NP BMP-2 ) displayed sustained in vitro release of BMP-2 for up to two weeks. Further in vitro studies indicated that bioinks composed of alginate and NP BMP-2 significantly induced osteogenesis of the MSCs compared with other controls, evidenced by enhanced calcium deposition, alkaline phosphatase activity, and gene expression of osteogenic markers. Our novel bioink consisting of widely used biocompatible components displays good printability, stability, and osteogenic inductivity, and holds strong potential for cell printing and bone tissue engineering applications., (Copyright © 2022. Published by Elsevier B.V.)

Bioprinting is an emerging technology for manufacturing cell-laden three-dimensional (3D) scaffolds, which are used to fabricate complex 3D constructs and provide specific microenvironments for supporting cell growth and differentiation. The development of bioinks with appropriate printability and specific bioactivities is crucial for bioprinting and tissue engineering applications, including bone tissue regeneration. Therefore, to produce functional bioinks for osteoblast printing and bone tissue formation, we formulated various nanocomposite hydrogel-based bioinks using natural and biocompatible biomaterials (i.e., alginate, tempo-oxidized cellulose nanofibrils (TOCNF), and polydopamine nanoparticles (PDANPs)). Rheological studies and printability tests revealed that bioinks containing 1.5% alginate and 1.5% TOCNF in the presence or absence of PDANP (0.5%) are suitable for 3D printing. Furthermore, in vitro studies of 3D-printed osteoblast-laden scaffolds indicated that the 0.5% PDANP-incorporated bioink induced significant osteogenesis. Overall, the bioink consisting of alginate, TOCNF, and PDANPs exhibited excellent printability and bioactivity (i.e., osteogenesis)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL)., Materials and Methods: In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B)., Results: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33)., Conclusion: The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Departing from traditional linguistic models, advances in deep learning have resulted in a new type of predictive (autoregressive) deep language models (DLMs). Using a self-supervised next-word prediction task, these models generate appropriate linguistic responses in a given context. In the current study, nine participants listened to a 30-min podcast while their brain responses were recorded using electrocorticography (ECoG). We provide empirical evidence that the human brain and autoregressive DLMs share three fundamental computational principles as they process the same natural narrative: (1) both are engaged in continuous next-word prediction before word onset; (2) both match their pre-onset predictions to the incoming word to calculate post-onset surprise; (3) both rely on contextual embeddings to represent words in natural contexts. Together, our findings suggest that autoregressive DLMs provide a new and biologically feasible computational framework for studying the neural basis of language., (© 2022. The Author(s).)

Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP have biopsy detectable prostate cancer (PCa) within 5 years. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. The aim of the present study was to examine the association between ASAP and subsequent diagnosis of clinically significant PCa (csPCa). The need for immediate repeat biopsy was also evaluated. We identified 212 patients with an ASAP diagnosis on their first biopsy at our institution between February 2006 and March 2018. Of these patients, 102 (48.1%) had at least one follow-up biopsy. Clinicopathologic features including rates of subsequent PCa and csPCa were assessed. Thirty-five patients subsequently underwent radical prostatectomy (RP). Their pathologic results were reviewed. csPCa was defined as the presence of Gleason score (GS) ≥ 3 + 4 in ≥ 1 biopsy core. Adverse pathology (AP) was defined as high-grade (primary Gleason pattern ≥ 4) or non-organ-confined disease (pT3/N1) after RP. Of 102 patients, 87 (85.3%), 13 (12.7%), and 2 (2.0%) had one, two, and three follow-up biopsies, respectively. Median time from the initial ASAP diagnosis to the 2nd follow-up biopsy and the last follow-up biopsy were 21.9 months (range 1-129 months) and 27.7 months (range 1-129 months), respectively. Of these patients, 46 (45.1%) were subsequently diagnosed with PCa, including 20 (19.6%) with csPCa. Only 2 (2.0%) patients had GS ≥ 8 disease. Five (4.9%) patients had number of positive cores > 3. Of 35 patients who subsequently underwent RP, seven (20%) had AP after RP and 17 (48.6%) showed GS upgrading. Of these 17 patients, the vast majority (16/17, 94.1%) had GS upgrading from 3 + 3 to 3 + 4. 45.1% of patients with an initial diagnosis of ASAP who had repeat prostate biopsy were subsequently diagnosed with PCa and 19.6% were found to have csPCa. Our findings add further evidence that after a diagnosis of ASAP, a repeat biopsy is warranted and that the repeat biopsy should not be postponed., (© 2021. The Author(s).)

In this study, the effects of heating rate and compressive strength on the spalling behavior of single-sided heated ring-restrained concrete with compressive strengths of 60 and 100 MPa were investigated. The vapor pressure and restrained stress inside the concrete were evaluated under fast- and slow-heating conditions. Regardless of the heating rate, the concrete vapor pressure and restrained stress increased as the temperature increased, and it was confirmed that spalling occurred in the 100-MPa concrete. Specifically, it was found that moisture migration and restrained stress inside the concrete varied depending on the heating rate. Under fast heating, moisture clogging and restrained stress occurred across the concrete surface, causing continuous surface spalling for the 100-MPa concrete. Under slow heating, moisture clogging occurred, and restrained stress continuously increased in the deep area of the concrete cross-section owing to the small internal temperature difference, resulting in explosive spalling for the 100-MPa concrete with a dense internal structure. Additionally, while the tensile strength of concrete is reduced by heating, stress in the heated surface direction is generated by restrained stress. The combination of stress in the heated concrete surface and the internal vapor pressure generates spalling. The experimental results confirm that heating rate has a significant influence on moisture migration and restrained stress occurrence inside concrete, which are important factors that determine the type of spalling.

The "Narratives" collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging., (© 2021. The Author(s).)

Concrete undergoes shrinkage regardless of the influence of external forces. The deformation of concrete is crucial for the structural stability of high-rise and large-scale buildings. In this study, the shrinkage and compressive creep of 70-90 MPa high-strength concrete used in high-rise buildings were evaluated based on the curing conditions (sealed/unsealed), and the existing prediction models were examined. It was observed that the curing condition does not significantly affect the mechanical properties of high-strength concrete, but the use of limestone coarse aggregate increases the elastic modulus when compared to granite coarse aggregate. The autogenous shrinkage of high-strength concrete is greater than that of normal-strength concrete owing to self-desiccation, resulting in a large variation from the value predicted by the model. The drying shrinkage was observed to be similar to that predicted by the model. Compressive creep was affected by the curing conditions, compressive strength, loading level, and loading age. The compressive creep of high-strength concrete varied significantly from the prediction results of ACI 209; ACI 209 was modified based on the measured values. The shrinkage and compressive creep characteristics of high-strength concrete must be reflected to predict the deformation of an actual structure exposed to various conditions.

Magnetic resonance imaging (MRI) is increasingly important in the detection and localization of prostate cancer. Regarding suspicious lesions on MRI, a targeted biopsy using MRI fused with ultrasound (US) is widely used. To achieve a successful targeted biopsy, a precise registration between MRI and US is essential. The purpose of our study was to show any decrease in errors using a real-time nonrigid registration technique for prostate biopsy. Nineteen patients with suspected prostate cancer were prospectively enrolled in this study. Registration accuracy was calculated by the measuring distance of corresponding points by rigid and nonrigid registration between MRI and US, and compared for rigid and nonrigid registration methods. Overall cancer detection rates were also evaluated by patient and by core. Prostate volume was measured automatically from MRI and manually from US, and compared to each other. Mean distances between the corresponding points in MRI and US were 5.32 ± 2.61 mm for rigid registration and 2.11 ± 1.37 mm for nonrigid registration ( p < 0.05). Cancer was diagnosed in 11 of 19 patients (57.9%), and in 67 of 266 biopsy cores (25.2%). There was no significant difference in prostate-volume measurement between the automatic and manual methods ( p = 0.89). In conclusion, nonrigid registration reduces targeting errors.

Background: Chordomas, which are rare malignant neoplasms arising from notochordal remnants, often cause gradually progressive clinical symptoms. Intradural cranial chordomas (ICCs) are extremely rare and generally have a favorable prognosis. However, the authors reported the case of a primary ICC originating in the pineal gland presenting with recurrent thalamic hemorrhage and displaying an aggressive postoperative clinical course., Observations: A 41-year-old man arrived at the emergency department with morning headaches and recurrent syncope that had lasted several months. Computed tomography and magnetic resonance imaging (MRI) revealed a pineal gland mass causing obstructive hydrocephalus and a subacute hematoma in the right thalamus. Three weeks after an endoscopic third ventriculostomy was performed, recurrent hemorrhage was observed in the right thalamus. The tumor was promptly removed surgically. The yellowish-white tumor did not exhibit abundant bleeding. No evidence of intratumoral hemorrhage around the hematoma pocket was found. Histopathological examination revealed the characteristics of a chordoma with minimal vascularity. MRI performed 10 weeks postoperatively for worsening headaches revealed abnormal enhancement of multiple cranial nerves, suggesting leptomeningeal seeding (LMS) of the tumor., Lessons: Despite radiotherapy and intrathecal chemotherapy, the patient's neurological status worsened; he died 2 years postoperatively. A pineal ICC may cause recurrent thalamic hemorrhage and potentially fatal LMS, even in the early postoperative period., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)