Useful blunders: Can automated speech recognition errors improve downstream dementia classification?

OBJECTIVES: We aimed to investigate how errors from automatic speech recognition (ASR) systems affect dementia classification accuracy, specifically in the "Cookie Theft" picture description task. We aimed to assess whether imperfect ASR-generated transcripts could provide valuable information for distinguishing between language samples from cognitively healthy individuals and those with Alzheimer's disease (AD). METHODS: We conducted experiments using various ASR models, refining their transcripts with post-editing techniques. Both these imperfect ASR transcripts and manually transcribed ones were used as inputs for the downstream dementia classification. We conducted comprehensive error analysis to compare model performance and assess ASR-generated transcript effectiveness in dementia classification. RESULTS: Imperfect ASR-generated transcripts surprisingly outperformed manual transcription for distinguishing between individuals with AD and those without in the "Cookie Theft" task. These ASR-based models surpassed the previous state-of-the-art approach, indicating that ASR errors may contain valuable cues related to dementia. The synergy between ASR and classification models improved overall accuracy in dementia classification. CONCLUSION: Imperfect ASR transcripts effectively capture linguistic anomalies linked to dementia, improving accuracy in classification tasks. This synergy between ASR and classification models underscores ASR's potential as a valuable tool in assessing cognitive impairment and related clinical applications.

Inflammation down regulates stromal cell-derived factor 1α in the early phase of pulpitis.

The key to prevent pulp necrosis in the early stage of pulpitis is to promote tissue repair, which begins with cell migration. Stromal cell-derived factor 1α (SDF-1α) has been proven to promote cell migration. Related research has so far concentrated on the biological effects of SDF-1α while its expression in pulpitis is still unclear. We investigated the effect of inflammation on SDF-1α in dental pulp and the underlying regulatory mechanisms. First, rat pulpitis models were established by exposing pulp. SDF-1α was decreased on the 3rd day but increased on the 7th day. Next, lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) was applied to dental pulp cells (DPCs). Within 24 h, SDF-1α decreased, but after 48 h, it steadily increased. Similarly, SDF-1α expression in human chronic pulpitis tissues was also increased. To investigate the effect of altered SDF-1α on DPC migration, cell supernatants collected following Pg.LPS treatment were utilized to stimulate DPCs, and the number of migrated cells was correlated with changes in SDF-1α secretion. Finally, we explored the regulatory mechanisms of SDF-1α down-regulation in the early phase of pulpitis. Within 24 h, JNK/c-Jun pathway was activated in DPC inflammation. When JNK pathway was suppressed, SDF-1α rose. Furthermore, tumor necrosis factor receptor 2 (TNFR2) and apoptosis signal-regulated kinase-interacting protein 1 (AIP1) were up-regulated. Knockdown of them abolished Pg.LPS-induced activation of JNK and c-Jun(Ser63) and significantly enhanced SDF-1α. Our findings indicated that in the early phase of pulpitis, inflammation suppressed SDF-1α by up-regulating TNFR2 and AIP1, which activated JNK/c-Jun(Ser63) pathway.

Wnt4 regulates bone metabolism through IKK-NF-κB and ROCK signaling under occlusal traumatic periodontitis.

BACKGROUND AND OBJECTIVE: Occlusal trauma is one of the most important local contributing factors of periodontitis. It has been reported that Wnt4, a noncanonical Wnt ligand, can inhibit osteoclast formation and inflammation and promote bone formation in vivo. However, the prospects of Wnt4 application in occlusal trauma and periodontitis have not yet been described. This study aimed to investigate the function and the corresponding mechanism of Wnt4 to regulate bone metabolism in occlusal trauma and periodontitis. MATERIAL AND METHODS: Osteogenic-induced MC3T3-E1 cells were treated with or without Porphyromonas gingivalis lipopolysaccharide (Pg. LPS) under cyclic uniaxial compressive stress. After treatment with mouse recombinant protein Wnt4 (rWnt4), the expression of osteogenic markers and activation of the IKK-NF-κB signaling pathway were evaluated in vitro. To investigate whether Wnt4 can promote osteogenesis via the ROCK signaling pathway, the expression of RhoA was evaluated in vitro. Finally, we evaluated the change in bone quantity and the activation of the IKK-NF-κB and ROCK signaling in mice with occlusal trauma and periodontitis to demonstrate the therapeutic efficacy of rWnt4 injection. RESULTS: Stimulation of traumatic force and Pg. LPS stimulation suppressed the expression of osteoblast markers, but their expression was rescued after rWnt4 treatment in vitro. In addition, the inhibition of the ROCK signaling pathway induced by force loading was reversed when rWnt4 was applied in vitro. Micro-CT, H&E, and TRAP staining of the mandibles showed increased bone loss in the occlusal trauma-aggravated periodontitis group, whereas it was rescued after rWnt4 injection. The expression levels of IκBα and p65 were upregulated in occlusal trauma and periodontitis-bearing mice, whereas the expression levels of Runx2 and RhoA were downregulated. After rWnt4 injection, remarkably upregulation of Runx2 and RhoA expression was observed in occlusal trauma and periodontitis- bearing mice. CONCLUSION: Wnt4 not only inhibits IKK-NF-κB signaling but also activates ROCK signaling to inhibit osteoclast formation and promote bone regeneration in occlusal trauma and periodontitis-bearing mice.

Fully automated detection of formal thought disorder with Time-series Augmented Representations for Detection of Incoherent Speech (TARDIS).

Formal thought disorder (ThD) is a clinical sign of schizophrenia amongst other serious mental health conditions. ThD can be recognized by observing incoherent speech - speech in which it is difficult to perceive connections between successive utterances and lacks a clear global theme. Automated assessment of the coherence of speech in patients with schizophrenia has been an active area of research for over a decade, in an effort to develop an objective and reliable instrument through which to quantify ThD. However, this work has largely been conducted in controlled settings using structured interviews and depended upon manual transcription services to render audio recordings amenable to computational analysis. In this paper, we present an evaluation of such automated methods in the context of a fully automated system using Automated Speech Recognition (ASR) in place of a manual transcription service, with "audio diaries" collected in naturalistic settings from participants experiencing Auditory Verbal Hallucinations (AVH). We show that performance lost due to ASR errors can often be restored through the application of Time-Series Augmented Representations for Detection of Incoherent Speech (TARDIS), a novel approach that involves treating the sequence of coherence scores from a transcript as a time-series, providing features for machine learning. With ASR, TARDIS improves average AUC across coherence metrics for detection of severe ThD by 0.09; average correlation with human-labeled derailment scores by 0.10; and average correlation between coherence estimates from manual and ASR-derived transcripts by 0.29. In addition, TARDIS improves the agreement between coherence estimates from manual transcripts and human judgment and correlation with self-reported estimates of AVH symptom severity. As such, TARDIS eliminates a fundamental barrier to the deployment of automated methods to detect linguistic indicators of ThD to monitor and improve clinical care in serious mental illness.

Oncolytic Vaccinia Virus Carrying Aphrocallistes vastus Lectin (oncoVV-AVL) Enhances Inflammatory Response in Hepatocellular Carcinoma Cells.

Aphrocallistes vastus lectin (AVL) is a C-type marine lectin derived from sponges. Our previous study demonstrated that oncolytic vaccinia virus carrying AVL (oncoVV-AVL) significantly enhanced the cytotoxicity of oncoVV in cervical cancer, colorectal cancer and hepatocellular carcinoma through the activation of Ras/ERK, MAPK/ERK and PI3K/Akt signaling pathways. In this study, the inflammatory response induced by oncoVV-AVL in a hepatocellular carcinoma cell (HCC) model was investigated. The results showed that oncoVV-AVL increased the levels of inflammatory cytokines including IL-6, IL-8 and TNF-α through activating the AP-1 signaling pathway in HCC. This study provides novel insights into the utilization of lectin AVL in the field of cancer therapy.

Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1.

Nonalcoholic fatty liver disease (NAFLD) is recognized as a metabolic disease characterized by hepatic steatosis. Despite the growing burden of NAFLD, approved pharmacological treatment is lacking. As an inhibitor of androgen receptor (AR), EPI-001 is being explored for the treatment of prostate cancer. This study aimed to investigate the potential of EPI-001 for treating NAFLD in free fatty acids (FFAs)-induced human hepatic cells and high-fat-high-sugar (HFHS)-feeding mice. Our results showed that EPI-001 reduced lipid accumulation in hepatic cells and ameliorated hepatic steatosis in mouse livers. Further exploration suggested that the effect of EPI-001 was associated with CYP2E1-mediated reduction of reactive oxygen species (ROS). This provides encouraging evidence for further studies on EPI-001 therapy for NAFLD.

The effect of NLRP inflammasome on the regulation of AGEs-induced inflammatory response in human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Diabetes influences the frequency and development of periodontitis. Inflammation of human periodontal ligament cells (HPDLCs) participates in this pathologic process. Hence, this study aims to explore whether advanced glycation end products (AGEs), by-products of diabetes, could exaggerate inflammation induced by muramyl dipeptide (MDP) in HPDLCs, and whether nucleotide-binding oligomerization domain-like receptors (NLRs) signaling pathway was involved. MATERIAL AND METHODS: Human periodontal ligament cells were pre-treated with 100 µg/mL AGEs for 24 hours and stimulated with 10 µg/mL MDP for 24 hours. IL-6, IL-1ß, and RAGE were detected, and the activation of NF-κB signaling pathway was observed. The expression of NLRs was evaluated with or without silencing RAGE or blocking NF-κB pathway under AGEs stimulation. Statistical analyses were performed by using independent sample t test. RESULTS: Advanced glycation end products induced significant increase of inflammatory cytokines in HPDLCs (P < 0.05). Results of western blot (WB) showed that after 45 minutes stimulation of AGEs, p-p65/p65 ratio peaked; AGEs promoted the expression of NLRP1, NLRP3, and apoptosis-associated speck-like protein containing a CARD (ASC). After silencing RAGE or blocking NF-κB pathway, the up-regulation of NLRs protein caused by AGEs was attenuated. Additionally, AGEs pre-treatment could enhance the inflammatory response of MDP and the expression of NLRs, which were demonstrated by more expression of IL-6, IL-1ß, NOD2, NLRP1, NLRP3, and ASC. CONCLUSION: Advanced glycation end products induced inflammatory response in HPDLCs via NLRP1-inflammasome and NLRP3-inflammasome activation in which NF-κB signal pathway was involved. Besides, AGEs promoted the inflammatory response of MDP via NOD2, NLRP1-inflammasome, and NLRP3-inflammasome.

Rapid continuous 3D printing of customizable peripheral nerve guidance conduits.

Engineered nerve guidance conduits (NGCs) have been demonstrated for repairing peripheral nerve injuries. However, there remains a need for an advanced biofabrication system to build NGCs with complex architectures, tunable material properties, and customizable geometrical control. Here, a rapid continuous 3D-printing platform was developed to print customizable NGCs with unprecedented resolution, speed, flexibility, and scalability. A variety of NGC designs varying in complexity and size were created including a life-size biomimetic branched human facial NGC. In vivo implantation of NGCs with microchannels into complete sciatic nerve transections of mouse models demonstrated the effective directional guidance of regenerating sciatic nerves via branching into the microchannels and extending toward the distal end of the injury site. Histological staining and immunostaining further confirmed the progressive directional nerve regeneration and branching behavior across the entire NGC length. Observational and functional tests, including the von Frey threshold test and thermal test, showed promising recovery of motor function and sensation in the ipsilateral limbs grafted with the 3D-printed NGCs.

Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison.

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography-mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Quantifying abnormal emotion processing: A novel computational assessment method and application in schizophrenia.

Abnormal emotion processing is a core feature of schizophrenia spectrum disorders (SSDs) that encompasses multiple operations. While deficits in some areas have been well-characterized, we understand less about abnormalities in the emotion processing that happens through language, which is highly relevant for social life. Here, we introduce a novel method using deep learning to estimate emotion processing rapidly from spoken language, testing this approach in male-identified patients with SSDs (n = 37) and healthy controls (n = 51). Using free responses to evocative stimuli, we derived a measure of appropriateness, or "emotional alignment" (EA). We examined psychometric characteristics of EA and its sensitivity to a single-dose challenge of oxytocin, a neuropeptide shown to enhance the salience of socioemotional information in SSDs. Patients showed impaired EA relative to controls, and impairment correlated with poorer social cognitive skill and more severe motivation and pleasure deficits. Adding EA to a logistic regression model with language-based measures of formal thought disorder (FTD) improved classification of patients versus controls. Lastly, oxytocin administration improved EA but not FTD among patients. While additional validation work is needed, these initial results suggest that an automated assay using spoken language may be a promising approach to assess emotion processing in SSDs.

TRESTLE: Toolkit for Reproducible Execution of Speech, Text and Language Experiments.

The evidence is growing that machine and deep learning methods can learn the subtle differences between the language produced by people with various forms of cognitive impairment such as dementia and cognitively healthy individuals. Valuable public data repositories such as TalkBank have made it possible for researchers in the computational community to join forces and learn from each other to make significant advances in this area. However, due to variability in approaches and data selection strategies used by various researchers, results obtained by different groups have been difficult to compare directly. In this paper, we present TRESTLE (Toolkit for Reproducible Execution of Speech Text and Language Experiments), an open source platform that focuses on two datasets from the TalkBank repository with dementia detection as an illustrative domain. Successfully deployed in the hackallenge (Hackathon/Challenge) of the International Workshop on Health Intelligence at AAAI 2022, TRESTLE provides a precise digital blueprint of the data pre-processing and selection strategies that can be reused via TRESTLE by other researchers seeking comparable results with their peers and current state-of-the-art (SOTA) approaches.

Recent advances in the nanoarchitectonics of metal-organic frameworks for light-activated tumor therapy.

Metal-organic frameworks (MOFs) have received extensive attention in tumor therapy because of their advantages, including large specific surface area, regular pore size, adjustable shape, and facile functionalization. MOFs are porous materials formed by the coordination bonding of metal clusters and organic ligands. This review summarized the most recent advancements in tumor treatment based on nMOFs. First, we discuss the classification of MOFs, which primarily include the series of isoreticular MOF (IRMOF), zeolitic imidazolate framework (ZIF), coordination pillared-layer (CPL), Materials of Institute Lavoisier (MIL), porous coordination network (PCN), University of Oslo (UiO) and Biological metal-organic frameworks (BioMOFs). Then, we discuss the use of nMOFs in antitumor therapy, including drug delivery strategies, photodynamic therapy (PDT), photothermal therapy (PTT), and combination therapy. Finally, the obstacles and opportunities in nMOFs are discussed.

UPLC-MS/MS simultaneous quantification of urinary circadian rhythm hormones and related metabolites: Application to air traffic controllers.

Civil aviation flight crew and civil aviation air traffic controllers are prone to circadian rhythm abnormalities, which can lead to a slew of other maladies. It could endanger people's health and provide a serious threat to the safety of civil aviation flights if it is not appropriately evaluated and addressed. Early detection of rhythm irregularities and prompt treatment for particular populations that are vulnerable to rhythm disorders are crucial for enhancing civil aviation safety. In general, monitoring of the classical circadian rhythm biomarkers (melatonin or cortisol) in plasma or saliva is an effective way to evaluate the rhythm status. Due to the challenging sample procedure and the trauma of plasma, urine sample testing has received an increasing amount of attention. While, urine circadian rhythm biomarkers have seldom been examined, and the relationship between urinary steroid hormones and melatonin is still poorly understood. In most cases, hormones are determined by immunoassays respectively, mainly enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). There are also reports describing the liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique as a method of melatonin or few steroid hormones quantification, however, the simultaneous detection of multiple rhythmic hormones in human urine is rarely reported. For the quantification of the rhythmic hormones in human urine, an accurate approach using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was devised in this work. Nine endogenous hormones (melatonin, 6-hydroxymelatonin, 6-sulfatoxymelatonin, cortisol, corticosterone, cortisone, testosterone, epitestosterone and androsterone), in human overnight urine, were quantified after solid phase extraction (SPE). A reverse phase HSS C18 column was used for chromatographic separation with a 9-minute gradient elution and deuterated analogues of each analyte were applied as internal standards. This method was successfully applied to the analysis of 596 overnight urine samples (23:00-9:00) collected from 84 air traffic controllers in the Beijing area during shift work. This study's findings showed a clear correlation not only between melatonin and its metabolites; cortisol-related metabolites, but also between melatonin metabolites and endogenous metabolites upstream and downstream of cortisol, implying that these two categories of hormones can be used as potential biological rhythm indicators to provide circadian rhythm data support for future studies on circadian rhythm disorders.

Deep Scale-Variant Network for Femur Trochanteric Fracture Classification with HP Loss.

Achieving automatic classification of femur trochanteric fracture from the edge computing device is of great importance and value for remote diagnosis and treatment. Nevertheless, designing a highly accurate classification model on 31A1/31A2/31A3 fractures from the X-ray is still limited due to the failure of capturing the scale-variant and contextual information. As a result, this paper proposes a deep scale-variant (DSV) network with a hybrid and progressive (HP) loss function to aggregate more influential representations of the fracture regions. More specifically, the DSV network is based on the ResNet and integrated with the designed scale-variant (SV) layer and HP loss, where the SV layer aims to enhance the representation ability to extract the scale-variant features, and HP loss is intended to force the network to condense more contextual clues. Furthermore, to evaluate the effect of the proposed DSV network, we carry out a series of experiments on the real X-ray images for comparison and evaluation, and the experimental results demonstrate that the proposed DSV network could outperform other classification methods on this classification task.

Light-activated nanomaterials for tumor immunotherapy.

Tumor immunotherapy mainly relies on activating the immune system to achieve antitumor treatment. However, the present tumor immunotherapy used in the clinic showed low treatment efficacy with high systematic toxicity. To overcome the shortcomings of traditional drugs for immunotherapy, a series of antitumor immunotherapies based on nanomaterials have been developed to enhance the body's antitumor immune response and reduce systematic toxicity. Due to the noninvasiveness, remote controllability, and high temporal and spatial resolution of light, photocontrolled nanomaterials irradiated by excitation light have been widely used in drug delivery and photocontrolled switching. This review aims to highlight recent advances in antitumor immunotherapy based on photocontrolled nanomaterials. We emphasized the advantages of nanocomposites for antitumor immunotherapy and highlighted the latest progress of antitumor immunotherapy based on photoactivated nanomaterials. Finally, the challenges and future prospects of light-activated nanomaterials in antitumor immunity are discussed.

EDTA Promotes the Mineralization of Dental Pulp In Vitro and In Vivo.

INTRODUCTION: Dentin regeneration is one of the main goals of vital pulp treatment in which the biological properties of dental pulp cells (DPCs) need to be considered. In our previous study, we showed that EDTA could enhance the stromal cell-derived factor 1 alpha-induced migration of DPCs. The purpose of this study was to explore the effects of EDTA on the mineralization of dental pulp in vitro and in vivo. METHODS: DPCs were obtained from human premolars or third molars. Alkaline phosphatase assays and alizarin red S staining were used to examine the degree of differentiation and mineralized nodule formation of DPCs. Real-time polymerase chain reaction and Western blot analysis were performed to detect the messenger RNA and protein expressions of mineralization-related markers in DPCs. Extracellular-regulated protein kinase and Smad inhibitors were used to study the roles of these 2 signaling pathways in this process. In addition, pulp exposures were created on 18 premolars of 2 beagle dogs (>12 months) using a high-speed dental handpiece. The experimental group (n = 9) was treated with 12% EDTA for 5 minutes, and the control group (n = 9) was treated with sterile saline for the same duration. Mineral trioxide aggregate was used for direct pulp capping followed by glass ionomer cement sealing. Samples were collected 3 months later, and the regenerated dentin was assessed by micro-computed tomographic and histologic analyses. RESULTS: Exposure to 12% EDTA promoted the activity of alkaline phosphatase, the formation of mineralized nodules, and the messenger RNA and protein expressions of mineralization-related markers in DPCs. Furthermore, the process of 12% EDTA enhancing the differentiation of DPCs was mediated by the extracellular-regulated protein kinase 1/2 signaling pathway and inhibited by the Smad2/3 signaling pathway. In vivo, compared with the control group, more regenerated dentin that had fewer tunnel defects was formed in the 12% EDTA-treated group. CONCLUSIONS: Our results showed that 12% EDTA could promote the mineralization of dental pulp in vitro and in vivo.

Multi-Dimensional Printing for Bone Tissue Engineering.

The development of 3D printing has significantly advanced the field of bone tissue engineering by enabling the fabrication of scaffolds that faithfully recapitulate desired mechanical properties and architectures. In addition, computer-based manufacturing relying on patient-derived medical images permits the fabrication of customized modules in a patient-specific manner. In addition to conventional 3D fabrication, progress in materials engineering has led to the development of 4D printing, allowing time-sensitive interventions such as programed therapeutics delivery and modulable mechanical features. Therapeutic interventions established via multi-dimensional engineering are expected to enhance the development of personalized treatment in various fields, including bone tissue regeneration. Here, recent studies utilizing 3D printed systems for bone tissue regeneration are summarized and advances in 4D printed systems are highlighted. Challenges and perspectives for the future development of multi-dimensional printed systems toward personalized bone regeneration are also discussed.

Roles of Porphyromonas gingivalis and its virulence factors in periodontitis.

Periodontitis is an infection-driven inflammatory disease, which is characterized by gingival inflammation and bone loss. Periodontitis is associated with various systemic diseases, including cardiovascular, respiratory, musculoskeletal, and reproductive system related abnormalities. Recent theory attributes the pathogenesis of periodontitis to oral microbial dysbiosis, in which Porphyromonas gingivalis acts as a critical agent by disrupting host immune homeostasis. Lipopolysaccharide, proteases, fimbriae, and some other virulence factors are among the strategies exploited by P. gingivalis to promote the bacterial colonization and facilitate the outgrowth of the surrounding microbial community. Virulence factors promote the coaggregation of P. gingivalis with other bacteria and the formation of dental biofilm. These virulence factors also modulate a variety of host immune components and subvert the immune response to evade bacterial clearance or induce an inflammatory environment. In this chapter, our focus is to discuss the virulence factors of periodontal pathogens, especially P. gingivalis, and their roles in regulating immune responses during periodontitis progression.

The Centroid Cannot Hold: Comparing Sequential and Global Estimates of Coherence as Indicators of Formal Thought Disorder.

Thought disorder (TD) as reflected in incoherent speech is a cardinal symptom of schizophrenia and related disorders. Quantification of the degree ofTD can inform diagnosis, monitoring, and timely intervention. Consequently, there has been an interest in applying methods ofdistributional semantics to quantify incoherence ofspoken language. Prior studies have generally involved few participants and utilized speech data collected in on-site structured interviews. In this paper we conduct a comprehensive evaluation ofapproaches to quantify incoherence using distributional semantics, including a novel variant that measures the global coherence oftext. This evaluation is conducted in the context of "audio diaries" collected from participants experiencing auditory verbal hallucinations using a smartphone application. Results reveal our novel global coherence metric using the centroid (weighted vector average) outperforms established approaches in their agreement with human annotators, supporting their preferential use in the context of short recordings ofunstructured and largely spontaneous speech.

Traumatic compressive stress inhibits osteoblast differentiation through long chain non-coding RNA Dancr.

BACKGROUND: Occlusal trauma is an important local contributing factor aggravating periodontal pocket and alveolar bone absorption in periodontal diseases. Our previous studies have found that occlusal trauma inhibited osteogenic differentiation through nuclear factor (NF)-κB signaling. To further investigate the underlying mechanism, the aim of this study was to explore the role of long chain non-coding differentiation antagonizing non-protein coding RNA (Dancr) in the inhibitory effect of traumatic stress on osteoblast differentiation. METHODS: We took the MC3T3-E1 cells as object in vitro research and stimulated cells with simple stress load, Dancr-siRNA + stress load, Dancr overexpression-plasmid + stress load. Quantitative real-time polymerase chain reaction was used to detect the RNA expression levels of Dancr, alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2). The protein expressions of Alp and Runx2 were tested by Western blot and the activity of Alp was qualitatively demonstrated by Alp staining. In addition, Western blot was performed to investigate the role of Dancr in affecting NF-κB signaling pathway. RESULTS: Traumatic compressive stress inhibited the expressions of Alp, Runx2, andDancr in MC3T3-E1 cells. Stress-induced inhibition of osteoblast differentiation was promoted after silencing Dancr. Overexpression of Dancr could alleviate the inhibitory effect of traumatic force on osteoblast differentiation to some extent. Furthermore, NF-κB signaling was activated after silencing Dancr, and the activated effect of traumatic force on NF-κB signaling could be alleviated through overexpression of Dancr to some extent. CONCLUSION: Traumatic compressive stress can indirectly activate the NF-κB signaling through downregulation of Dancr, thereby inhibiting osteogenic differentiation.