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Abstract Focal cortical dysplasia type I (FCD I) is the most common cause of pharmaco-resistant epilepsy with the poorest prognosis. To understand the epileptogenic mechanisms of FCD I, we obtained tissue resected from patients with FCD I epilepsy, and from tumor patients as control. Using whole-cell patch clamp in acute human brain slices, we investigated the cellular properties of fast-spiking interneurons (FSINs) and pyramidal neurons (PNs) within the ictal onset zone. In FCD I epilepsy, FSINs exhibited lower firing rates from slower repolarization and action potential broadening, while PNs had increased firing. Importantly, excitatory synaptic drive of FSINs increased progressively with the scale of cortical activation as a general property across species, but this relationship was inverted towards net inhibition in FCD I epilepsy. Further comparison with intracranial electroencephalography (iEEG) from the same patients revealed that the spatial extent of pathological high-frequency oscillations (pHFO) was associated with synaptic events at FSINs.

BackgroundAs the population ages and the prevalence of dementia increases, there is a growing emphasis on the importance of cognitive training to prevent dementia. A smartphone application-based cognitive training software program, BeauBrain Trainer (BBT), has been developed to provide better access to cognitive training for older adults. Numerous studies have revealed the effectiveness of cognitive training using a cognitive assessment tool. However, relatively few studies have evaluated brain activation using brain imaging as a result of improved cognitive function.MethodsAll participants were required to download the BBT, an Android-based application for cognitive training, onto their own smartphone or tablet computer and to engage in cognitive training at home. Older adults without dementia were enrolled in this study, including 51 participants in the intervention group and 50 participants in the control group. The BBT comprised a set of 12 cognitive tasks, including two tasks in each of the following six cognitive domains: attention, language, calculation, visuospatial function, memory, and frontal/executive function. Each cognitive task was divided into four blocks based on its level of difficulty. A 16-week cognitive training was designed to carry out cognitive tasks using a total of 48 blocks (12 tasks × 4 levels) for at least 1.5 h per day, 5 days per week. All participants in the intervention group were given BBT tasks that gradually increased in difficulty level, which they submitted through a smartphone application daily for 16 weeks. The researchers monitored the participants’ task performance records on the website and encouraged participants to engage in cognitive training through regular contact. This study was conducted to investigate the improvement in cognitive function and the activation pattern of the frontal cortex in older adults participating in smartphone application-based cognitive training. The cognitive assessment tool was the BeauBrain cognitive screening test (CST), a tablet-based computerized cognitive screening test. The activation pattern of the frontal cortex was measured using functional near-infrared spectroscopy (fNIRS). Additionally, this study aimed to determine the positive effects of cognitive training on everyday functioning and psychological states using a questionnaire.ResultsOf 101 participants, 85 older adults without dementia (84.1%) who completed the study protocol were included in the statistical analysis. There were 41 participants (80.3%) in the intervention group and 44 participants (88.0%) in the control group. A two-way repeated-measures analysis of variance (ANOVA) was used to compare the cognitive scores over a 16-week period between the intervention and control groups. According to the CST results, the intervention group exhibited a statistically significant increase in the language subtest scores, specifically the phonemic word fluency test, compared to those of the control group. The fNIRS results revealed greater activation in the dorsolateral prefrontal cortex during the STROOP incongruent task in the intervention group than did the control group. However, the effectiveness of cognitive training was not observed across a variety of rating scales, including everyday functioning, depression, self-efficacy, attention, and subjective memory complaints.ConclusionThis study revealed that a smartphone-based cognitive training application led to improvements in phonemic generative naming ability and activation of the prefrontal cortex in older adults without dementia. This study is meaningful because it confirmed that cognitive training is partially effective in enhancing frontal lobe function. It also provided information on the brain mechanisms related to the effects of cognitive training using fNIRS.

It is challenging to control the growth of colloidal III-V quantum dots, due to complex reaction pathways. Here, the authors isolate a single-crystalline tetrapod species as a late-stage intermediate and use it as a tailored-growth platform in colloidal synthesis.

Objective Cerebral hemodynamic and metabolic changes may occur during the rewarming phase of targeted temperature management in post cardiac arrest patients. Yet, studies on different rewarming rates and patient outcomes are limited. This study aimed to investigate post cardiac arrest patients who were rewarmed with different rewarming rates after 24 hours of hypothermia and the association of these rates to the neurologic outcomes. Methods This study retrospectively investigated post cardiac arrest patients treated with targeted temperature management and rewarmed with rewarming rates of 0.15°C/hr and 0.25°C/hr. The association of the rewarming rate with poor neurologic outcomes (cerebral performance category score, 3 to 5) was investigated. Results A total of 71 patients were analyzed (0.15°C/hr, n=36; 0.25°C/hr, n=35). In the comparison between 0.15°C/hr and 0.25°C/hr, the poor neurologic outcome did not significantly differ (24 [66.7%] vs. 25 [71.4%], respectively; P=0.66). In the multivariate analysis, the rewarming rate of 0.15°C/hr was not associated with the 1-month neurologic outcome improvement (odds ratio, 0.54; 95% confidence interval, 0.16 to 1.69; P=0.28). Conclusion The rewarming rates of 0.15°C/hr and 0.25°C/hr were not associated with the neurologic outcome difference in post cardiac arrest patients.

Mathematics teachers’ knowledge is considered one of the most critical factors in instruction and student achievement. As such, various studies have focused on mathematics teachers’ knowledge. Despite the expansion of the field, however, a systematic review was rarely implemented. Therefore, this study aimed to identify major research topics and trends on mathematics teachers’ knowledge by analyzing abstracts of 3485 scholarly articles published from 1987 to 2021. Using a text-mining technique, 11 underlying topics were found in the articles. The topics were classified based on their relationships and the following four groups were identified: “assessment”, “teachers’ knowledge for teaching”, “students’ knowledge and understanding”, and “teachers’ professional learning”. Over time, the analysis of research trends showed that professional development is the most popular topic, followed by pedagogical content knowledge and students’ mathematical understanding. Moreover, the popularity of these topics has not changed considerably over time. This study provides implications based on these results.

Objective: Reclassification of variants of uncertain significance (VUS) may allow for improved cancer prevention, screening, targeted therapy, as well as surgical and reproductive decisionmaking. We reinterpreted BRCA1/2 VUS results in patients with epithelial ovarian cancer and assessed whether the clinical significance of VUS was changed. Methods: We retrospectively reviewed the medical records of 253 epithelial ovarian cancer patients who underwent BRCA1/2 genetic testing from 2010 to 2020. The VUSs in BRCA1/2 were reanalyzed using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines (ACMG/AMP 2015 guidelines) and the VUS were reclassified into 5 categories: "pathogenic," "likely pathogenic," "VUS," "likely benign," and "benign." Results: Forty-nine patients were identified as carrying either one or more VUS in BRCA1/2. Among the 49 patients, 44 patients (89.9%) were reclassified as benign (including likely benign) or pathogenic (including likely pathogenic) variants. Four patients (8.2%) were reclassified as "pathogenic or likely pathogenic," 40 patients (81.6%) were reclassified as either "benign" or "likely benign," and the remaining 5 patients (10.2%) were still classified as VUS category. There was a family history of ovarian cancer or breast cancer in the group of patients reclassified as a pathogenic variant (p=0.053). Although there was no statistically significant difference in survival, the survival rate of patients classified as pathogenic was higher. Conclusion: Reclassification of VUS should be done periodically, which is crucial to improve clinical decision-making. In particular, reclassification is necessary for VUS patients with a family history of ovarian cancer or breast cancer. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to develop an artificial intelligence (AI) model using deep learning techniques to diagnose dens evaginatus (DE) on periapical radiography (PA) and compare its performance with endodontist evaluations. In total, 402 PA images (138 DE and 264 normal cases) were used. A pre-trained ResNet model, which had the highest AUC of 0.878, was selected due to the small number of data. The PA images were handled in both the full (F model) and cropped (C model) models. There were no significant statistical differences between the C and F model in AI, while there were in endodontists (p = 0.753 and 0.04 in AUC, respectively). The AI model exhibited superior AUC in both the F and C models compared to endodontists. Cohen’s kappa demonstrated a substantial level of agreement for the AI model (0.774 in the F model and 0.684 in C) and fair agreement for specialists. The AI’s judgment was also based on the coronal pulp area on full PA, as shown by the class activation map. Therefore, these findings suggest that the AI model can improve diagnostic accuracy and support clinicians in diagnosing DE on PA, improving the long-term prognosis of the tooth.

Objective: Ovarian cancer has highest mortality rate among gynecological cancers. In particular, in the case of peritoneal metastasis, the prognosis is poor. As a solution to this, hyperthermic intraperitoneal chemotherapy (HIPEC) has begun to be implemented. In this study, we sought to compare the results of HIPEC conducted at our hospital based on existing studies' results. Methods: We retrospectively reviewed the electronic medical record (EMR) of patients who were diagnosed with ovarian cancer and underwent HIPEC between January 2018 and December 2021. We reviewed EMR focusing on surgical outcomes and prognostic factors after HIPEC. Among these, the surgical results of patients who underwent HIPEC through primary or interval cytoreductive surgery (ICS) were compared with those who underwent HIPEC after recurrence. Results: Recurrence occurred in 76.5% of patients who underwent HIPEC and the average operation time was 501 minutes. The average of estimated blood loss was 796 mL, and postoperative side effects occurred in 8.8%. We compared the prognostic factors of patients who underwent ICS and HIPEC with those who took HIPEC after recurrence. The results were not significant, but both overall survival (OS) and progression free survival (PFS) were longer by 13 months and 9 months, respectively, in patients who underwent ICS and HIPEC (p=0.0694, p=0.1391). Conclusion: Based on existing study, the results of HIPEC at our hospital showed that the operation time and duration of hospitalization were longer. Although it was not a significant result, considering that OS and PFS results in ICS and HIPEC, it can be assumed that HIPEC after recurrence is not effective. [ABSTRACT FROM AUTHOR]

Objective: Screening is necessary for women with family members diagnosed with breast or ovarian cancer to prevent ovarian or breast cancer. We investigated the frequency of breast cancer in ovarian cancer patients and analyzed the related factors. Methods: We retrospectively reviewed the medical records of 253 epithelial ovarian cancer patients who had completed a cancer pedigree from 2010 to 2020. We compared and analyzed differences between patients who had both ovarian cancer and breast cancer and those who had only ovarian cancer according to family history, BRCA mutation status, and time of onset. Results: In our study, among 253 patients with epithelial ovarian cancer, 20 had been treated for both ovarian cancer and breast cancer. Ten patients developed breast cancer after ovarian cancer and another 10 developed ovarian cancer after breast cancer. Patients treated for both breast and ovarian cancer exhibited a higher incidence of a family history of ovarian or breast cancer compared to those with only ovarian cancer (40.0% vs. 9.9%, p=0.001). Additionally, patients with both breast and ovarian cancer had a higher incidence of BRCA mutation than those with only ovarian cancer (50.0% vs. 20.2%, p=0.002). However, 9 patients (45.0%) had both ovarian and breast cancer without a family history of either cancer or BRCA mutation. Conclusion: Even in cases where there is no family history or genetic mutation, breast cancer could develop in ovarian cancer patients at a similar frequency. Therefore, periodic breast cancer screening is essential for all epithelial ovarian cancer patients, regardless of family history or genetic mutation. [ABSTRACT FROM AUTHOR]

Abstract Determining the exact positional relationship between mandibular third molar (M3) and inferior alveolar nerve (IAN) is important for surgical extractions. Panoramic radiography is the most common dental imaging test. The purposes of this study were to develop an artificial intelligence (AI) model to determine two positional relationships (true contact and bucco-lingual position) between M3 and IAN when they were overlapped in panoramic radiographs and compare its performance with that of oral and maxillofacial surgery (OMFS) specialists. A total of 571 panoramic images of M3 from 394 patients was used for this study. Among the images, 202 were classified as true contact, 246 as intimate, 61 as IAN buccal position, and 62 as IAN lingual position. A deep convolutional neural network model with ResNet-50 architecture was trained for each task. We randomly split the dataset into 75% for training and validation and 25% for testing. Model performance was superior in bucco-lingual position determination (accuracy 0.76, precision 0.83, recall 0.67, and F1 score 0.73) to true contact position determination (accuracy 0.63, precision 0.62, recall 0.63, and F1 score 0.61). AI exhibited much higher accuracy in both position determinations compared to OMFS specialists. In determining true contact position, OMFS specialists demonstrated an accuracy of 52.68% to 69.64%, while the AI showed an accuracy of 72.32%. In determining bucco-lingual position, OMFS specialists showed an accuracy of 32.26% to 48.39%, and the AI showed an accuracy of 80.65%. Moreover, Cohen’s kappa exhibited a substantial level of agreement for the AI (0.61) and poor agreements for OMFS specialists in bucco-lingual position determination. Determining the position relationship between M3 and IAN is possible using AI, especially in bucco-lingual positioning. The model could be used to support clinicians in the decision-making process for M3 treatment.

When diagnosing orofacial pain, clinicians should also consider non-odontogenic origin and systemic diseases as possible etiological factors, along with odontogenic origin. This case report aimed to provide information for early detection of orofacial pain of cardiac origin by dentists, when pain due to coronary artery disease is the only presenting symptom. A 60-year-old male patient with unexplained isolated bilateral jaw pain that had persisted for the past 5 years was referred to a dentist by an anesthesiologist who suspected temporomandibular joint disorder. In oral examination, no specific pathological changes were observed in the oral cavity, including teeth, surrounding alveolar bone, and buccal mucosa. Magnetic resonance imaging and conventional radiography showed no pathological destruction or abnormalities of bone and soft tissue in the temporomandibular joint region. However, pain was precipitated by ordinary daily activities, and the pain alleviating factor was rest. Eventually, the patient was referred to a cardiologist for further evaluation since his pain was induced by physical activity. Coronary artery disease (CAD) was diagnosed using coronary computed tomography angiography, and the pain was considered to be angina pectoris. Percutaneous coronary intervention was successfully done for the patient, after which his orofacial symptoms disappeared. To conclude, isolated craniofacial pain of cardiac origin may lead to patients seeking dental care or visiting orofacial pain clinics. In these settings, dentists and orofacial pain specialists may contribute to the diagnosis of CAD and refer patients for cardiac evaluation and appropriate management.

Mental health problems in childhood and adolescence (e. g., attention deficits, problems in emotional understanding and subclinical levels of anxiety) are reported to develop further in adulthood and/or to increase the risk of developing mental health disorders in adulthood. Although it is important to provide treatment or prevention interventions for children and adolescents in order to reduce the risk of the further development of mental health problems, the pharmacological and behavioral treatments for this age group have limitations (e.g., limited access, unsustainable treatment effects and the lack of engagement in intervention). In order to overcome the limitations of conventional treatments, the use of digital technology, especially video games for this age group, is suggested. In order to be accepted as clinical interventions, objective evidence for the therapeutic effects of digital therapeutic that used video games to treat or prevent targeted mental health problems are required. Thus, this review aims to explore whether game-based digital therapeutics (DTx) for children and adolescents showed therapeutic effects on targeted mental health problems. As game-based DTx are suggested to show sustained therapeutic effects and the transfer of cognitive functions, it also reviews the maintenance of the therapeutic effects of DTx and the extent of the transfer of cognitive functions. Game-based DTx that are developed to treat or prevent mental health problems (e.g., attention deficit, depression) in children and adolescents are found to show therapeutic effects on targeted mental health problems despite the limitations (e.g., small sample size, limited investigation of the sustainability). This review would contribute to the understanding of whether there is objective evidence of the therapeutic effects of digital therapeutics using video games that deliver treatment or prevention interventions for mental health problems in children and adolescents.

Abstract Orthopantomogram (OPG) is important for primary diagnosis of temporomandibular joint osteoarthritis (TMJOA), because of cost and the radiation associated with computed tomograms (CT). The aims of this study were to develop an artificial intelligence (AI) model and compare its TMJOA diagnostic performance from OPGs with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karas’ ResNet model and trained to classify images into three categories: normal, indeterminate OA, and OA. This study included 1189 OPG images confirmed by cone-beam CT and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI was developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJOA in a similar manner to an expert and was in most accord with CBCT when the indeterminate OA category was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJOA from OPGs in most general practice clinics where OMFR experts or CT are not available.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status.Clinical Trial Registrationclinicaltrials.gov (NCT02964572).

SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

Abstract Background Unlike the emphasis on negative results of video games such as the impulsive engagement in video games, cognitive training studies in individuals with cognitive deficits showed that characteristics of video game elements were helpful to train cognitive functions. Thus, this study aimed to have a more balanced view toward the video game playing by reviewing genres of commercial video games and the association of video games with cognitive functions and modulating factors. Literatures were searched with search terms (e.g. genres of video games, cognitive training) on database and Google scholar. Results video games, of which purpose is players’ entertainment, were found to be positively associated with cognitive functions (e.g. attention, problem solving skills) despite some discrepancy between studies. However, the enhancement of cognitive functions through video gaming was limited to the task or performance requiring the same cognitive functions. Moreover, as several factors (e.g. age, gender) were identified to modulate cognitive enhancement, the individual difference in the association between video game playing and cognitive function was found. Conclusion Commercial video games are suggested to have the potential for cognitive function enhancement. As understanding the association between video gaming and cognitive function in a more balanced view is essential to evaluate the potential outcomes of commercial video games that more people reported to engage, this review contributes to provide more objective evidence for commercial video gaming.

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention.

BackgroundThe World Health Organization announced the inclusion of gaming disorder (GD) in the International Classification of Diseases, 11th Revision, despite some concerns. However, video gaming has been associated with the enhancement of cognitive function. Moreover, despite comparable extensive video gaming, pro gamers have not shown any of the negative symptoms that individuals with GD have reported. It is important to understand the association between extensive video gaming and alterations in brain regions more objectively. ObjectiveThis study aimed to systematically explore the association between extensive video gaming and changes in cognitive function by focusing on pro gamers and individuals with GD. MethodsStudies about pro gamers and individuals with GD were searched for in the PubMed and Web of Science databases using relevant search terms, for example, “pro-gamers” and “(Internet) gaming disorder.” While studies for pro gamers were searched for without date restrictions, only studies published since 2013 about individuals with GD were included in search results. Article selection was conducted by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. ResultsBy following the PRISMA guidelines, 1903 records with unique titles were identified. Through the screening process of titles and abstracts, 86 full-text articles were accessed to determine their eligibility. A total of 18 studies were included in this systematic review. Among the included 18 studies, six studies included pro gamers as participants, one study included both pro gamers and individuals with GD, and 11 studies included individuals with GD. Pro gamers showed structural and functional alterations in brain regions (eg, the left cingulate cortex, the insula subregions, and the prefrontal regions). Cognitive function (eg, attention and sensorimotor function) and cognitive control improved in pro gamers. Individuals with GD showed structural and functional alterations in brain regions (eg, the striatum, the orbitofrontal cortex, and the amygdala) that were associated with impaired cognitive control and higher levels of craving video game playing. They also showed increased cortical thickness in the middle temporal cortex, which indicated the acquisition of better skills. Moreover, it was suggested that various factors (eg, gaming expertise, duration or severity of GD, and level of self-control) seemed to modulate the association of extensive video game playing with changes in cognitive function. ConclusionsAlthough a limited number of studies were identified that included pro gamers and/or individuals who reported showing symptoms of GD for more than 1 year, this review contributed to the objective understanding of the association between extensive video game playing and changes in cognitive function. Conducting studies with a longitudinal design or with various comparison groups in the future would be helpful in deepening the understanding of this association.

Purpose: Ultrasonography is widely used for examining breast mass. We used the Breast Imaging-Reporting and Data System (BI-RADS) to characterize breast lesions found on ultrasonography. Among various ultrasound techniques, we used S-DetectTM (Samsung Medison Co., Ltd, Seoul, Korea), which supports the morphological analysis of breast masses found according to BI-RADS. In addition, we compared the breast surgeons’ categorization of breast masses with that by S-DetectTM. Methods: Breast surgeons evaluated the breast masses found using ultrasonography between April 2016 and December 2016. A total of 139 masses, which were categorized as BI-RADS 3 or 4, from 112 patients were reevaluated by S-DetectTM before performing vacuum-assisted resection or surgical excision. Results: Of the 139 masses, 118 were benign tumors and 21 were malignant tumors. With regard to the diagnostic performance, the sensitivity of categorization was 95% for breast surgeons, but the sensitivity was relatively lower for S-detectTM (85%). However, the specificity and accuracy of S-detectTM were 70.6% and 74.1%, respectively, which were higher than those values obtained from breast surgeons (18.5% and 30.9%, respectively). Conclusion: S-detectTM can be used by breast surgeons as a diagnostic aid when evaluating and diagnosing breast masses found on ultrasonography.

Abstract Background Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants. Results We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific. Conclusions Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.

Nonhost resistance, a resistance of plant species against all nonadapted pathogens, is considered the most durable and efficient immune system of plants but yet remains elusive. The underlying mechanism of nonhost resistance has been investigated at multiple levels of plant defense for several decades. In this review, we have comprehensively surveyed the latest literature on nonhost resistance in terms of preinvasion, metabolic defense, pattern-triggered immunity, effector-triggered immunity, defense signaling, and possible application in crop protection. Overall, we summarize the current understanding of nonhost resistance mechanisms. Pre- and postinvasion is not much deviated from the knowledge on host resistance, except for a few specific cases. Further insights on the roles of the pattern recognition receptor gene family, multiple interactions between effectors from nonadapted pathogen and plant factors, and plant secondary metabolites in host range determination could expand our knowledge on nonhost resistance and provide efficient tools for future crop protection using combinational biotechnology approaches.[Graphic: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative condition of the TMJ led by a pathological tissue response of the joint under mechanical loading. It is characterized by the progressive destruction of the internal surfaces of the joint, which can result in debilitating pain and joint noise. Panoramic imaging can be used as a basic screening tool with thorough clinical examination in diagnosing TMJ OA. This paper proposes an algorithm that can extract the condylar region and determine its abnormality by using convolutional neural networks (CNNs) and Faster region-based CNNs (R-CNNs). Panoramic images are collected retrospectively and 1000 images are classified into three categories—normal, abnormal, and unreadable—by a dentist or orofacial pain specialist. Labels indicating whether the condyle is detected and its location enabled more clearly recognizable panoramic images. The uneven proportion of normal to abnormal data is adjusted by duplicating and rotating the images. An R-CNN model and a Visual Geometry Group-16 (VGG16) model are used for learning and condyle discrimination, respectively. To prevent overfitting, the images are rotated ±10° and shifted by 10%. The average precision of condyle detection using an R-CNN at intersection over union (IoU) >0.5 is 99.4% (right side) and 100% (left side). The sensitivity, specificity, and accuracy of the TMJ OA classification algorithm using a CNN are 0.54, 0.94, and 0.84, respectively. The findings demonstrate that classifying panoramic images through CNNs is possible. It is expected that artificial intelligence will be more actively applied to analyze panoramic X-ray images in the future.

The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found that FK506-binding protein 8 (FKBP8) also induced DLK degradation. We identified the lysine 271 residue in the kinase domain as a major site of DLK ubiquitination and SUMO3 conjugation and was thus responsible for regulating FKBP8-mediated proteasomal degradation that was inhibited by the substitution of the lysine 271 to arginine. FKBP8-mediated degradation of DLK is mediated by autophagy pathway because knockdown of Atg5 inhibited DLK destabilization. We show that in vivo overexpression of FKBP8 delayed the progression of axon degeneration and suppressed neuronal death after axotomy in sciatic and optic nerves. Taken together, this study identified FKBPL and FKBP8 as novel DLK-interacting proteins that regulate DLK stability via the ubiquitinproteasome and lysosomal protein degradation pathways. [ABSTRACT FROM AUTHOR]