Evaluation of a Nondepleted Plasma Multiprotein-Based Model for Discriminating Psychiatric Disorders Using Multiple Reaction Monitoring-Mass Spectrometry: Proof-of-Concept Study.

Psychiatric evaluation relies on subjective symptoms and behavioral observation, which sometimes leads to misdiagnosis. Despite previous efforts to utilize plasma proteins as objective markers, the depletion method is time-consuming. Therefore, this study aimed to enhance previous quantification methods and construct objective discriminative models for major psychiatric disorders using nondepleted plasma. Multiple reaction monitoring-mass spectrometry (MRM-MS) assays for quantifying 453 peptides in nondepleted plasma from 132 individuals [35 major depressive disorder (MDD), 47 bipolar disorder (BD), 23 schizophrenia (SCZ) patients, and 27 healthy controls (HC)] were developed. Pairwise discriminative models for MDD, BD, and SCZ, and a discriminative model between patients and HC were constructed by machine learning approaches. In addition, the proteins from nondepleted plasma-based discriminative models were compared with previously developed depleted plasma-based discriminative models. Discriminative models for MDD versus BD, BD versus SCZ, MDD versus SCZ, and patients versus HC were constructed with 11 to 13 proteins and showed reasonable performances (AUROC = 0.890-0.955). Most of the shared proteins between nondepleted and depleted plasma models had consistent directions of expression levels and were associated with neural signaling, inflammatory, and lipid metabolism pathways. These results suggest that multiprotein markers from nondepleted plasma have a potential role in psychiatric evaluation.

Mechanistic decoupling of exonuclease III multifunctionality into AP endonuclease and exonuclease activities at the single-residue level.

Bacterial exonuclease III (ExoIII) is a multifunctional enzyme that uses a single active site to perform two conspicuous activities: (i) apurinic/apyrimidinic (AP)-endonuclease and (ii) 3'→5' exonuclease activities. The AP endonuclease activity results in AP site incision, while the exonuclease activity results in the continuous excision of 3' terminal nucleobases to generate a partial duplex for recruiting the downstream DNA polymerase during the base excision repair process (BER). The key determinants of functional selection between the two activities are poorly understood. Here, we use a series of mutational analyses and single-molecule imaging to unravel the pivotal rules governing these endo- and exonuclease activities at the single amino acid level. An aromatic residue, either W212 or F213, recognizes AP sites to allow for the AP endonuclease activity, and the F213 residue also participates in the stabilization of the melted state of the 3' terminal nucleobases, leading to the catalytically competent state that activates the 3'→5' exonuclease activity. During exonucleolytic cleavage, the DNA substrate must be maintained as a B-form helix through a series of phosphate-stabilizing residues (R90, Y109, K121 and N153). Our work decouples the AP endonuclease and exonuclease activities of ExoIII and provides insights into how this multifunctional enzyme controls each function at the amino acid level.

Prediction of psychosis: model development and internal validation of a personalized risk calculator.

BACKGROUND: Over the past two decades, early detection and early intervention in psychosis have become essential goals of psychiatry. However, clinical impressions are insufficient for predicting psychosis outcomes in clinical high-risk (CHR) individuals; a more rigorous and objective model is needed. This study aims to develop and internally validate a model for predicting the transition to psychosis within 10 years. METHODS: Two hundred and eight help-seeking individuals who fulfilled the CHR criteria were enrolled from the prospective, naturalistic cohort program for CHR at the Seoul Youth Clinic (SYC). The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression was used to develop a predictive model for a psychotic transition. We performed k-means clustering and survival analysis to stratify the risk of psychosis. RESULTS: The predictive model, which includes clinical and cognitive variables, identified the following six baseline variables as important predictors: 1-year percentage decrease in the Global Assessment of Functioning score, IQ, California Verbal Learning Test score, Strange Stories test score, and scores in two domains of the Social Functioning Scale. The predictive model showed a cross-validated Harrell's C-index of 0.78 and identified three subclusters with significantly different risk levels. CONCLUSIONS: Overall, our predictive model showed a predictive ability and could facilitate a personalized therapeutic approach to different risks in high-risk individuals.

Impaired error-related processing in patients with first-episode psychosis and subjects at clinical high risk for psychosis: An event-related potential study.

AIM: Impaired event-related potential (ERP) indices reflecting performance-monitoring systems have been consistently reported in patients with schizophrenia. However, whether these impairments exist from the beginning of the early phase of psychosis, such as in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis, has not yet been clearly ascertained. METHODS: Thirty-seven FEP patients, 22 CHR subjects, and 22 healthy controls (HC) performed a visual go/no-go task so that three ERP components associated with performance monitoring-error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe) -could be assessed. Repeated-measures analysis of variance (ANOVA) with age and sex as covariates was used to compare ERN, CRN, and Pe across the groups. RESULTS: Repeated-measures ANOVA with age and sex as covariates revealed that compared with HC, FEP patients and CHR subjects showed significantly smaller ERN amplitudes at the Fz (F = 4.980, P = 0.009) and FCz (F = 3.453, P = 0.037) electrode sites. Neither CRN nor Pe amplitudes showed significant differences across the FEP, CHR, and HC groups. CONCLUSION: These findings suggest that performance monitoring is already compromised during the early course of psychotic disorders, evident in FEP patients and CHR subjects, as reflected in the reduced ERN amplitude. Considering these findings, ERN could serve as a potential indicator of early-stage psychosis.

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study.

OBJECTIVE: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. METHODS: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. RESULTS: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate-left primary motor cortex/right dorsal rostral putamen-anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen-anterior cingulate cortex functional connectivity predicted improvement in general functioning. CONCLUSION: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.

Prognostic significance of Human epidermal growth factor receptor-2 expression in patients with resectable gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and clinicopathologic factors and overall survival rate in patients who underwent curative gastrectomy for gastric adenocarcinoma. METHODS: Among patients who underwent curative gastrectomy for gastric adenocarcinoma at Inje University Paik Hospital from January 2012 to December 2015, 782 patients underwent an immunohistochemical analysis to evaluate HER2 expression levels. Clinicopathologic records that were collected from a gastric cancer database were retrospectively reviewed to identify clinicopathologic factors and survival rates of the patients. RESULTS: HER2 overexpression was detected in 166 patients (21.2%). There was a statistically significant correlation between HER2 expression level and sex (p = 0.013), histologic differentiation (p < 0.001), Lauren classification (p < 0.001), and T pathologic stage (p = 0.022). There were no statistically significant relationships between HER2 expression level and overall 5-year survival rate (p = 0.775) and overall 5-year survival rate of gastric adenocarcinoma classified according to the TNM stage (stage I: p = 0.756, stage II: p = 0.571, stage III: p = 0.704). The HER2 expression level was not affected by the overall 5-year survival rate in the uni- and multivariate analyses. CONCLUSIONS: In this study, the HER2 overexpression rate in gastric adenocarcinoma was 21.2% and was observed in well- and moderately differentiated types according to histologic differentiation, intestinal type according to the Lauren classification, male, and low T stage. There was no correlation between HER2 expression level and overall 5-year survival rate, and HER2 expression level was not associated with independent prognostic factors.

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24-48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3-1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells.

Pharmacotherapy for obsessive-compulsive disorder: Real-world evidence from a 10-year retrospective data analysis.

We investigated pharmacotherapy trends for obsessive-compulsive disorder (OCD) patients at a Korean tertiary hospital from 2008 to 2017. Out of 1894 patients, 82.9% received at least one psychotropic medication, with prescription rates increasing over time. The most frequently prescribed drug classes were selective serotonin reuptake inhibitors (SSRIs, 80.5%), anxiolytics (57.5%), antipsychotics (47.2%), other antidepressants (21.1%), and mood stabilizers (18.4%). Combination therapy was administered to 79.7% of medicated patients, with SSRIs, anxiolytics, and antipsychotics being the most common combination. Comorbidities significantly increased the prescription rates of all psychotropic classes (P < 0.001). Our study offers insights that may aid in bridging the gap between OCD treatment guidelines and real-world clinical practice.

Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

The COVID-19 Vaccine Safety Research Center: a cornerstone for strengthening safety evidence for COVID-19 vaccination in the Republic of Korea.

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC's initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC's second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

Compromised Cerebello-Thalamic White Matter Integrity in Medication-Free Patients With Obsessive-Compulsive Disorder.

OBJECTIVE: The cerebello-thalamic tract is the only efferent white matter (WM) bundle of the cerebellum that connects the cerebellum to the thalamus and has recently attracted much attention in obsessive-compulsive disorder (OCD) with its integral role in higher order cognitive functions commonly impaired in OCD patients. Previous neuroimaging studies have shown that the cerebello-thalamic circuit is functionally impaired in OCD patients. However, the WM integrity of the cerebello-thalamic tract in OCD, which may underly functional abnormalities of the cerebello-thalamic circuit, is not yet sufficiently understood. Therefore, the current study aimed to elucidate whether compromised cerebello-thalamic WM integrity is observed in medication-free OCD patients. METHODS: In this study, diffusion tensor imaging was acquired from 106 medication-free OCD patients and 105 matched healthy controls (HCs). Probabilistic tractography was then used to reconstruct the cerebello-thalamic tract with accurate anatomical features. Three diffusion indices (fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD) were measured from the reconstructed bilateral cerebello-thalamic tract and then compared between groups. RESULTS: We found that patients with OCD showed significantly increased MD and RD in the right cerebello-thalamic tract compared to HCs, and there was no difference in FA between groups. CONCLUSION: Our findings may indicate the underlying structural abnormalities of the dysfunctional cerebello-thalamic circuit in OCD patients. Therefore, our findings are expected to provide novel insights into the pathophysiology of OCD on the cerebello-thalamic WM architecture, extending our knowledge from the existing functional neurobiological model of OCD.

Perfectionism, test anxiety, and neuroticism determines high academic performance: a cross-sectional study.

BACKGROUND: Academic performance is an important issue for Korean students. Various psychological factors contribute to academic performance. We aimed to evaluate the psychological factors that affect academic performance integratively. METHODS: A total of 102 academic high achievers and 120 comparison participants were recruited. We evaluated psychological factors (test anxiety, perfectionism, personality traits, resilience, and self-efficacy) and measured academic performance using the College Scholastic Ability Test and the current college grade. We compared psychological factors and academic performance between the academic high achiever and comparison groups. Multiple linear regression was then conducted to identify the significant psychological factors for high academic performance. Further, we used cluster analysis to classify the comparison group by the significant psychological factors and compared them among clusters and academic high achievers to determine the psychological characteristics of academic high achievers. RESULTS: The academic high achiever group showed lower test anxiety (p = .002), less neuroticism (p = .001), higher self-efficacy (p = .028), and less socially prescribed perfectionism (p < .001) than the comparison group. Multiple linear regression results (p = .020) clarified that neuroticism (p = .020), test anxiety level (p = .047), and perfectionism (p = .035) were important factors predicting better academic performance. Academic high achievers had moderate test anxiety and perfectionism levels, with the best performance on the College Scholastic Ability Test. CONCLUSIONS: Neuroticism, test anxiety levels, and perfectionism are important psychological factors for high academic performance. Interventions targeting these factors may help to improve academic accomplishments.

Impact of long-acting injectable aripiprazole on the concomitant medication and antipsychotic polypharmacy: a retrospective, observational study of 127 patients with psychosis.

Antipsychotic polypharmacy (APP) has become prevalent over the years, but several concerns have been raised over APP. Accumulating evidence suggests that aripiprazole long-acting injectable (LAI) may reduce the rate of APP, but the association remains speculative. This retrospective observational study included 127 patients with psychosis and observed them for 1.8 ±â€…1.3 years, up to 4 years. Prescription data of antipsychotics (APs), mood stabilisers, benzodiazepines, and anti-extrapyramidal side effect medications were obtained at baseline and the last observation. Daily chlorpromazine equivalent (CPZ) dose of APs decreased from 124.40 ±â€…235.35 mg to 77.95 ±â€…210.36 mg (P = 0.027). The daily dose of anticholinergics and beta-blockers also significantly decreased after introducing aripiprazole LAI. Among the patients having APP, the number of concurrent APs along with daily CPZ dose of APs decreased after initiation of aripiprazole LAI from 1.28 ±â€…0.62 to 0.85 ±â€…0.73 (P < 0.001) and 298.33 ±â€…308.70 mg to 155.43 ±â€…280.53 mg (P = 0.004), respectively. Treatment with aripiprazole LAI for up to 4 years in patients with psychosis was associated with a reduced number of prescribed APs in patients having an APP and a reduced dose of APs and concurrent psychotropic medications.

Validation of the Bipolar Prodrome Symptom Interview and Scale-Abbreviated Prospective (BPSS-AP) in a clinical sample and healthy controls.

BACKGROUND: After the existence of a bipolar disorder (BD) prodrome was established, the development of clinical rating instruments has become relevant that are sufficiently brief to be implemented in real-world clinical practice and that are designed to identify individuals at-risk for BD. This study aimed to validate a shorter version of the Bipolar Prodrome Symptom Interview and Scale (BPSS), the BPSS-Abbreviated Prospective (BPSS-AP), for use among clinical populations. METHODS: Altogether, 104 adults, comprising individuals diagnosed with BD (n = 17, mania: n = 8, hypomania: n = 9), with major depressive disorder (MDD, n = 38, all currently depressed), and healthy controls (HCs, n = 49), underwent BPSS-AP interviews. The psychometric properties of the BPSS-AP were evaluated, including internal consistency, convergent validity, discriminant validity, and factor structure. RESULTS: The median (IQR) age was 29 (23-38), 40 (23-55), and 25 (22-28) years, for the BD, MDD, and HC groups, respectively. The BPSS-AP showed excellent internal consistency (Cronbach's α = 0.95). Convergent validity between the BPSS-AP and Young Mania Rating Scale (YMRS) was high (r > 0.7). The BPSS-AP discriminated patients with BD from those with MDD (P < .001) and from HCs (P < .001). LIMITATIONS: The study design precludes assessment of the predictive validity of the BPSS-AP. CONCLUSIONS: This study found that the BPSS-AP, a more concise and feasible version of the semi-structured interview for identifying individuals at risk of developing BD, has satisfactory psychometric properties. There is room for further validation and application of the BPSS-AP in clinical settings to evaluate its utility in research and clinical care.

A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee.

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA's COVID-19 vaccination data and the National Health Insurance Service's claims data. The CoVaSC's 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Characteristics of adverse reactions among antipsychotic drugs using the Korean Adverse Event Reporting System database from 2010 to 2019.

BACKGROUND: Retrospective studies using spontaneous reporting system databases have provided a great understanding of adverse drug reactions (ADRs) in the real world, complementing the data obtained from randomized controlled trials. However, there have been few reports on large-scale epidemiological studies on the adverse effects of antipsychotics in Asia. AIM: This study aimed to investigate the characteristics of antipsychotic ADRs using a nationwide pharmacovigilance database. METHODS: Data were collected from the Korea Adverse Event Reporting System database between 2010 and 2019. The study subjects were selected using the International Classification of Disease codes for diseases related to psychosis and Electronic Data Interchange codes for amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The causality assessment of "possible," "probable," or "certain" by the World Health Organization-Uppsala Monitoring Center System causality category was selected. All data were descriptively analyzed. RESULTS: In total, 5067 adverse events associated with antipsychotic drugs were reported. The antipsychotics that commonly resulted in ADRs were quetiapine (47.7%), olanzapine (11.3%), and clozapine (10.7%). Serious ADRs were most commonly observed with clozapine. Gastrointestinal and central nervous system problems occurred within a month when ADRs were classified according to the time of onset. In contrast, metabolic and bone marrow-related symptoms occurred after long-term use. Sedation and nausea were the most common ADRs in children and adolescents, whereas constipation and dizziness were common in adults and the elderly. CONCLUSIONS: This study extends our knowledge of antipsychotic ADRs in the Asian population.

Sex differences in the behavioral inhibition system and ventromedial prefrontal cortex connectivity.

The reinforcement sensitivity theory proposes brain-behavioral systems that underlie individual differences in sensitivity to punishment and reward. Such trait sensitivity is assessed using the behavioral inhibition/activation system (BIS/BAS) scales. Recent studies have reported sex-linked neuroanatomical correlates of the BIS/BAS, especially in the regions belonging to the valuation and salience networks that are associated with the representation of subjective value (SV), whereas less effort has been focused on investigating the neurofunctional aspects associated with sex differences in the BIS/BAS. We tested whether functional connectivity (FC) of the regions associated with the representation of SV mediates the relationship between sex and BIS sensitivity in healthy young adults by using resting-state functional magnetic resonance imaging data and self-reported BIS/BAS measures. Compared with males, females had heightened BIS sensitivity and increased FC between the ventromedial prefrontal cortex (vmPFC) seed and posterior parietal areas; this FC mediated the impact of sex on BIS sensitivity. Given that the observed vmPFC FC maps are considered part of the default-mode network, which is involved in ruminative processes, and that the BIS is associated with rumination and negative affect, our results may have implications for psychiatric disorders such as depression and anxiety, both of which have high incidence in females.

In vivo optical properties of cortical tubers in children with tuberous sclerosis complex (TSC): a preliminary investigation.

PURPOSE: Medically refractory epilepsy caused by cortical tubers resulting from tuberous sclerosis complex (TSC) often requires surgical intervention. The locations of cortical tubers generally are determined by preoperative magnetic resonance imaging (MRI). In this pilot study, we explored the feasibility of using the optical characteristics of cortical tubers as a potential means to guide their resection intraoperatively. METHODS: Optical characteristics of normal cortex and cortical tubers were measured intraoperatively using diffuse reflectance spectroscopy in three children undergoing epilepsy surgery for drug-resistant seizures. Unique diffuse reflectance spectroscopic features of cortical tubers were identified and their physiologic associations determined. KEY FINDINGS: Diffuse reflectance spectra revealed several features that distinguish cortical tubers from normal cortex. In tubers, diffuse reflectance intensities at oxy- and deoxyhemoglobin isobestic points, like 500, 530, and 570 nm, were consistently higher than those in normal cortex. According to the profile of diffuse reflectance spectra from 520-580 nm, hemoglobin oxygenation in tubers often was lower than in normal cortex. SIGNIFICANCE: Albeit preliminary, our findings suggest that the optical characteristics of cortical tubers differ from intervening normal cortex, likely reflecting the lower cerebral blood volumes and reduced hemoglobin oxygenation of cortical tubers. The results of this study can be used to design biomedical instruments that aid tuberectomies.

Comparative analysis of intra-articular injection of steroid and/or sodium hyaluronate in adhesive capsulitis: prospective, double-blind, randomized, placebo-controlled study.

BACKGROUND: Few studies have reported the effects of simultaneous injections of corticosteroid (CS) and hyaluronic acid (HA) on adhesive capsulitis (AC) of the shoulder. This study investigated the synergistic effects of simultaneous intra-articular injections of CS and compared them to those of CS or HA alone. METHOD: Sixty patients with AC were enrolled in this randomized, placebo-controlled trial. The participants were divided into 4 groups: saline, CS, HA, and CS with HA groups. The primary outcome measure was changes in the Shoulder Pain and Disability Index (SPADI) scores at one month. The secondary outcome measures included changes in pain, range of motion, muscle strength, and additional shoulder functional scores at 1 day, 1 week, and 1, 3, and 6 months after injection. RESULTS: After 1 month, changes of the SPADI scores were significantly higher in the CS with HA group (-58.4%) than those in the saline (-7.7%) and HA (-14.4%) groups. The score changed more in the CS with HA group than that in the CS group (-43.7%), but there was no significant difference. In the changes in pain, the CS with HA group showed significantly better and faster effects than the saline and HA groups. In the changes of range of motion, functional scores, the CS with HA group showed better results than the saline and HA groups. CONCLUSION: In the treatment of AC, the simultaneous injection of CS and HA was more effective in improving SPADI scores at one month after injection than a single injection of CS or HA.

Unsupervised multi-sense language models for natural language processing tasks.

Existing language models (LMs) represent each word with only a single representation, which is unsuitable for processing words with multiple meanings. This issue has often been compounded by the lack of availability of large-scale data annotated with word meanings. In this paper, we propose a sense-aware framework that can process multi-sense word information without relying on annotated data. In contrast to the existing multi-sense representation models, which handle information in a restricted context, our framework provides context representations encoded without ignoring word order information or long-term dependency. The proposed framework consists of a context representation stage to encode the variable-size context, a sense-labeling stage that involves unsupervised clustering to infer a probable sense for a word in each context, and a multi-sense LM (MSLM) learning stage to learn the multi-sense representations. Particularly for the evaluation of MSLMs with different vocabulary sizes, we propose a new metric, i.e., unigram-normalized perplexity (PPLu), which is also understood as the negated mutual information between a word and its context information. Additionally, there is a theoretical verification of PPLu on the change of vocabulary size. Also, we adopt a method of estimating the number of senses, which does not require further hyperparameter search for an LM performance. For the LMs in our framework, both unidirectional and bidirectional architectures based on long short-term memory (LSTM) and Transformers are adopted. We conduct comprehensive experiments on three language modeling datasets to perform quantitative and qualitative comparisons of various LMs. Our MSLM outperforms single-sense LMs (SSLMs) with the same network architecture and parameters. It also shows better performance on several downstream natural language processing tasks in the General Language Understanding Evaluation (GLUE) and SuperGLUE benchmarks.