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Abstract Stroke is a neurological complication that can occur in patients admitted to the intensive care unit (ICU) for non-neurological conditions, leading to increased mortality and prolonged hospital stays. The incidence of stroke in ICU settings is notably higher compared to the general population, and delays in diagnosis can lead to irreversible neurological damage. Early diagnosis of stroke is critical to protect brain tissue and treat neurological defects. Therefore, we developed a machine learning model to diagnose stroke in patients with acute neurological manifestations in the ICU. We retrospectively collected data on patients’ underlying diseases, blood coagulation tests, procedures, and medications before neurological symptom onset from 206 patients at the Chungbuk National University Hospital ICU (July 2020–July 2022) and 45 patients at Chungnam National University Hospital between (July 2020–March 2023). Using the Categorical Boosting (CatBoost) algorithm with Bayesian optimization for hyperparameter selection and k-fold cross-validation to mitigate overfitting, we analyzed model-feature relationships with SHapley Additive exPlanations (SHAP) values. Internal model validation yielded an average accuracy of 0.7560, sensitivity of 0.8959, specificity of 0.7000, and area under the receiver operating characteristic curve (AUROC) of 0.8201. External validation yielded an accuracy of 0.7778, sensitivity of 0.7500, specificity of 0.7931, and an AUROC of 0.7328. These results demonstrated the model’s effectiveness in diagnosing stroke in non-neurological ICU patients with acute neurological manifestations using their electronic health records, making it valuable for the early detection of stroke in ICU patients.

Background Acute ischemic stroke is a disease with multiple etiologies. Therefore, identifying the mechanism of acute ischemic stroke is fundamental to its treatment and secondary prevention. The Trial of Org 10172 in Acute Stroke Treatment classification is currently the most widely used system, but it often has a limitations of classifying unknown causes and inadequate inter-rater reliability. Therefore, we attempted to develop a three-dimensional (3D)-convolutional neural network (CNN)-based algorithm for stroke lesion segmentation and subtype classification using only the diffusion and apparent diffusion coefficient information of patients with acute ischemic stroke. Methods This study included 2,251 patients with acute ischemic stroke who visited our hospital between February 2013 and July 2019. Results The segmentation model for lesion segmentation in the training set achieved a Dice score of 0.843±0.009. The subtype classification model achieved an average accuracy of 81.9%, with accuracies of 81.6% for large artery atherosclerosis, 86.8% for cardioembolism, 72.9% for small vessel occlusion, and 86.3% for control. Conclusion We developed a model to predict the mechanism of cerebral infarction using diffusion magnetic resonance imaging, which has great potential for identifying diffusion lesion segmentation and stroke subtype classification. As deep learning systems are gradually developing, they are becoming useful in clinical practice and applications.

Abstract Respiratory distress is a common chief complaint in neonates admitted to the neonatal intensive care unit. Despite the increasing use of non-invasive ventilation in neonates with respiratory difficulty, some of them require advanced airway support. Delayed intubation is associated with increased morbidity, particularly in urgent unplanned cases. Early and accurate prediction of the need for intubation may provide more time for preparation and increase safety margins by avoiding the late intubation at high-risk infants. This study aimed to predict the need for intubation within 3 h in neonates initially managed with non-invasive ventilation for respiratory distress during the first 48 h of life using a multimodal deep neural network. We developed a multimodal deep neural network model to simultaneously analyze four time-series data collected at 1-h intervals and 19 variables including demographic, physiological and laboratory parameters. Evaluating the dataset of 128 neonates with respiratory distress who underwent non-invasive ventilation, our model achieved an area under the curve of 0.917, sensitivity of 85.2%, and specificity of 89.2%. These findings demonstrate promising results for the multimodal model in predicting neonatal intubation within 3 h.

We present a global optimization routine for the variational quantum algorithms, which utilizes the dynamic tunneling flow. Originally designed to leverage information gathered by a gradient-based optimizer around local minima, we adapt the conventional dynamic tunneling flow to exploit the distance measure of quantum states, resolving issues of extrinsic degeneracy arising from the parametrization of quantum states. Our global optimization algorithm is applied to the variational quantum eigensolver for the transverse-field Ising model to demonstrate the performance of our routine while comparing it with the conventional dynamic tunneling method, which is based on the Euclidean distance measure on the parameter space.

Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma and has frequent recurrence instances. Although PTC recurrence has been predicted using predictors established using various features and techniques, its early detection is still challenging. To address this issue, it is aimed to develop a deep‐learning model that utilizes not only the initial medical records but also the thyroid function tests (TFTs) performed periodically post‐surgery. Herein, a novel multimodal prediction model, called the hybrid architecture for multimodal analysis (HAMA), that can analyze numeric and time‐series data simultaneously, is proposed. For quantitative evaluation, fourfold cross validation is conducted on data of 1613 PTC patients including 63 locoregional recurrence patients, and the HAMA is achieved the following performance: sensitivity (0.9688); specificity (0.9781); F1‐score (0.7943); and area under the receiver‐operating characteristic curve, AUROC (0.9863). Furthermore, a real‐time prediction simulation is conducted at 6‐month intervals by reconstructing the data of each patient into real‐time data. It is demonstrated in the real‐time simulation results that the HAMA predicts PTC recurrence at least 1.5 years in advance by recalculating the recurrence probability using the additional follow‐up data. To the best of the knowledge, the HAMA is the first deep‐learning model to reflect continuous change in the physical condition of a patient post‐surgery.

X-ray imaging is one of the most widely used security measures for maintaining airport and transportation security. Conventional X-ray imaging systems typically apply tone-mapping (TM) algorithms to visualize high-dynamic-range (HDR) X-ray images on a standard 8-bit display device. However, X-ray images obtained through traditional TM algorithms often suffer from halo artifacts or detail loss in inter-object overlapping regions, which makes it difficult for an inspector to detect unsafe or hazardous objects. To alleviate these problems, this article proposes a deep learning-based TM method for X-ray inspection. The proposed method consists of two networks called detail-recovery network (DR-Net) and TM network (TM-Net). The goal of DR-Net is to restore the details in the input HDR image, whereas TM-Net aims to compress the dynamic range while preserving the restored details and preventing halo artifacts. Since there are no standard ground-truth images available for the TM of X-ray images, we propose a novel loss function for unsupervised learning of TM-Net. We also introduce a dataset synthesis technique using the Beer-Lambert law for supervised learning of DR-Net. Extensive experiments comparing the performance of our proposed method with state-of-the-art TM methods demonstrate that the proposed method not only achieves visually compelling results but also improves the quantitative performance measures such as FSITM and HDR-VDP-2.2.

For indirect contrast enhancement, researchers have proposed various transformation functions based on histogram equalization and gamma correction. However, these transformation functions tend to result in over-enhancement artifacts such as noise amplification, mean brightness change, and detail loss. To overcome the limitations of conventional transformation functions, this paper introduces a novel sigmoid function based on the contrast sensitivity of human brightness perception. In the proposed method, the contrast sensitivity of the human retina is modeled as an exponential function of the log-intensity, and a transformation function is derived using the sensitivity model as the exponent of Steven's power law. We also present a parameter optimization method that maintains the mean brightness of the input image and stretches the image histogram while minimizing information loss. Experimental results demonstrate that the proposed method has low computational complexity and outperforms the state-of-the-art methods in terms of contrast enhancement performance, mean brightness preservation, and detail preservation.

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.

Background: The need for informatics and genomics training in pathology is critical, yet limited resources for such training are available. In this study we sought to critically test the hypothesis that the incorporation of a wiki (a collaborative writing and publication tool with roots in "Web 2.0") in a combined informatics and genomics course could both (1) serve as an interactive, collaborative educational resource and reference and (2) actively engage trainees by requiring the creation and sharing of educational materials. Materials and Methods: A 2-week full-time course at our institution covering genomics, research, and pathology informatics (GRIP) was taught by 36 faculty to 18 second- and third-year pathology residents. The course content included didactic lectures and hands-on demonstrations of technology (e.g., whole-slide scanning, telepathology, and statistics software). Attendees were given pre- and posttests. Residents were trained to use wiki technology (MediaWiki) and requested to construct a wiki about the GRIP course by writing comprehensive online review articles on assigned lectures. To gauge effectiveness, pretest and posttest scores for our course were compared with scores from the previous 7 years from the predecessor course (limited to informatics) given at our institution that did not utilize wikis. Results: Residents constructed 59 peer-reviewed collaborative wiki articles. This group showed a 25% improvement (standard deviation 12%) in test scores, which was greater than the 16% delta recorded in the prior 7 years of our predecessor course (P = 0.006). Conclusions: Our use of wiki technology provided a wiki containing high-quality content that will form the basis of future pathology informatics and genomics courses and proved to be an effective teaching tool, as evidenced by the significant rise in our resident posttest scores. Data from this project provide support for the notion that active participation in content creation is an effective mechanism for mastery of content. Future residents taking this course will continue to build on this wiki, keeping content current, and thereby benefit from this collaborative teaching tool.

Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI), new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology.

Background: NUP98 rearrangements (NUP98r), associated with various hematologic malignancies, involve more than 30 partner genes. Despite their clinical significance, reports on the clinicopathological characteristics of rare NUP98r remain limited. We investigated the characteristics of patients with myeloid neoplasms harboring NUP98r among those identified as having 11p15 translocation in chromosomal analysis. Methods: We retrospectively reviewed results from bone marrow chromosomal analyses conducted between 2011 and 2023 and identified 15 patients with 11p15 translocation. Subsequently, NUP98r were evaluated using FISH and/or reverse transcription PCR, and clinical and laboratory data of the patients were analyzed. Results: NUP98r were identified in 11 patients initially diagnosed as having AML (N=8), myelodysplastic syndrome (N=2), or chronic myelomonocytic leukemia (N=1), with a median age of 44 yrs (range, 4-77 yrs). Three patients had a history of chemotherapy. In total, five NUP98 fusions were identified: NUP98::DDX10 (N=3), NUP98::HOXA9 (N=2), NUP98::PSIP1 (N=2), NUP98::PRRX1 (N=1), and NUP98::HOXC11 (N=1). Patients with NUP98r exhibited a poor prognosis, with a median overall survival of 12.0 months (95% confidence interval [CI], 3.4-29.6 months) and a 5-yr overall survival rate of 18.2% (95% CI, 5.2%-63.7%). Conclusions: Our study revealed the clinical and genetic characteristics of patients with myeloid neoplasms harboring rare and non-cryptic NUP98r. Given its association with poor prognosis, a comprehensive evaluation is crucial for identifying previously underdiagnosed NUP98r in patients with myeloid neoplasms. [ABSTRACT FROM AUTHOR]

Objective: High-risk human papillomavirus (HR-HPV) infection is a leading cause of cervical cancer, of which human papillomavirus (HPV)-16 and HPV-18 account for about 70% of cases. Since HPV infection is common, it is important to focus on the HPV genotypes that pose the highest risk for effective cervical cancer screening. In this study, we evaluated the clinical usefulness of HPV-16/HPV-18 genotyping for cervical cancer screening. Methods: A total of 86,022 women aged 25 years or older was analyzed in this study. Sensitivity, specificity, positive predictive value, and negative predictive value of HPV genotyping and cytology were analyzed. In addition, we subdivided participants into two groups according to cytology results, negative for intraepithelial lesion of malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US), and analyzed absolute risk (AR) and relative risk (RR) of cervical intraepithelial neoplasia (CIN) 3 or worse according to HPV genotype. Results: The AR of CIN 3 or worse was 77.0 times higher in HR-HPV-positive compared to HR-HPV-negative. Compared to 12 other HR-HPV-positive, the AR of CIN 3 or worse was 4.2 times higher in HPV-16 and/or HPV-18 positive. This finding was more evident in women with NILM than in women with ASC-US. The RR of CIN 3 or worse was 7.0 in women with NILM and 4.5 in women with ASC-US. Conclusion: Regardless of the cytology results, the risk of CIN 3 or worse was higher in HPV-16/HPV-18 than in other HR-HPV. HPV-16/HPV-18 genotyping is recommended to screen women with a high risk of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective : Post-stroke shoulder pain (PSSP) is a common complication that limits the range of motion (ROM) of the shoulder, the patient’s rehabilitation and in turn, affects the patients’ quality of life (QoL). Several treatment modalities such as sling, positioning, strapping, functional electrical stimulation, and nerve block have been suggested in literatures, however none of the treatments had long-term effects for PSSP. In this study, the authors evaluated clinical efficacy of pulsed radiofrequency (PRF) neuromodulation on the suprascapular nerve for PSSP, and suggested it as a potential treatment with long-term effect. Methods : This retrospective case series was conducted at a single center, a private practice institution. From 2013 to 2021, 13 patients with PSSP underwent PRF neuromodulation of the suprascapular nerve. The primary outcome measure was the Visual analog scale (VAS) score. The secondary outcome measurements included the shoulder ROM, Disability assessment scale (DAS), modified Ashworth scale, modified Rankin scale (mRS), and EuroQol-5 dimension-3L questionnaire (EQ-5D-3L) scores. These parameters were evaluated before PRF modulation, immediately after PRF modulation, and every 3 months until the final follow-up visit. Results : Six men and seven women were enrolled, and all patients were followed-up for a minimum of 12 months. The mean VAS score was 7.07 points before PRF neuromodulation and 2.38 points immediately post-procedure. Shoulder ROM for abduction and flexion, DAS for pain, mRS, and EQ-5D-3L demonstrated marked improvement. No complications were reported. Conclusion : PRF neuromodulation of the suprascapular nerve is an effective modality in patients with PSSP, and has long-term effect of pain relief, improvement of QoL. [ABSTRACT FROM AUTHOR]

The entry into a hyper-connected society increases the generalization of communication using SNS. Therefore, research to analyze big data accumulated in SNS and extract meaningful information is being conducted in various fields. In particular, with the recent development of Deep Learning, the performance is rapidly improving by applying it to the field of Natural Language Processing, which is a language understanding technology to obtain accurate contextual information. In this paper, when a chatbot system is applied to the healthcare domain for counseling about diseases, the performance of NLP integrated with machine learning for the accurate classification of medical subjects from text-based health counseling data becomes important. Among the various algorithms, the performance of Bidirectional Encoder Representations from Transformers was compared with other algorithms of CNN, RNN, LSTM, and GRU. For this purpose, the health counseling data of Naver Q&A service were crawled as a dataset. KoBERT was used to classify medical subjects according to symptoms and the accuracy of classification results was measured. The simulation results show that KoBERT model performed high performance by more than 5% and close to 18% as large as the smallest. [ABSTRACT FROM AUTHOR]

Cacao (Theobroma cacao L.) is considered as economic importance crop playing a major role as source of chocolate industries for production of both chocolate candy and cocoa butter. Despite the advantages of cacao in industrial sector, understanding the global structure of cacao chloroplast genome plays a crucial role in explaining phylogenetic relationships and cultivar identification. This study aimed to perform phylogenetic analysis of cacao genotypes and develop DNA barcode markers using cacao chloroplast sequences. Chloroplast genome sequencing of two cacao genotypes (DR-1 and Sca-12) was conducted by the Illumina Miseq platform. Phylogenetic analysis of 12 cacao genotypes including two genotypes sequenced in this study (DR-1 and Sca-12) and ten genotypes previously sequenced (HQ336404, EET-64, ICS-01, ICS-06, ICS-39, Pentagonum, Sca-6, Stahel, Amelonado, and Criollo-22) showed a clear separation between bulk and fine types. This result demonstrated the usefulness of chloroplast sequences in revealing phylogenetic relatedness. Based on comparative chloroplast genome analysis of two cacao genotypes, DR-1 and Sca-12, three insertion/deletion (InDel) markers named as Theca_indel01, Theca_indel02, and Theca_indel03 which designed from the regions of trnA-UGC-rrn23, trnK-UUU-rps16, and rps16 intron, respectively were successfully developed to reveal barcode system for cacao genetic discrimination. Overall, these findings would provide valuable insight into the chloroplast genome structure of cacao plant, as well as information about the benefits of chloroplast sequences for constructing phylogenetic relationships and developing DNA barcode markers. [ABSTRACT FROM AUTHOR]

Sediment quality assessment guidelines(SQAGs) for seven trace elements were suggested to build an assessment system of freshwater sediment quality for a regulatory program in Korea. In this study, current one-step SQAGs were divided into three levels based on the probability of toxicity occurrence, namely, the threshold-effect-level(TEL), the probable-effect-level(PEL), and the apparent-effect-threshold(AET). A sediment toxicity database consisting of field-collected sediments and toxicity results from three different species were used to derive TEL, PEL, and AET. The ambient background concentrations of trace elements in freshwater sediments were used instead of the TEL values because TEL values were lower than the ambient background levels. To validate the reliability of the new SQAGs, a separate sediment toxicity database based on G. sobaegensis was used. When the mean quotient value for the PEL was 0.34, the reliability reached a maximum of 87% with a positive predictive value of 94% and a negative predictive value of 85%. These results showed the newly derived SQAGs were very useful for assessing and predicting the toxicity of field sediments in Korea. Finally, ambient background concentrations, a mean quotient of PEL of 0.34, and AETs were used to classify the quality of the field-collected sediments into four categories. [ABSTRACT FROM AUTHOR]

Few cases of bilateral axillary extramammary Paget's disease (EMPD) have been reported. We performed surgical excision and reconstruction in a patient with bilateral axillary EMPD after consultation with dermatology. A dermatologist determined the boundaries of the lesion through Mohs micrographic surgery, and a plastic surgeon excised the lesion and reconstructed the resulting defect. Skin grafts were simultaneously performed to reconstruct the bilateral axillae. After the operation, the reconstructed site healed well, but the range of motion of both shoulders was reduced. After referral to a doctor specializing in rehabilitation, the patient was diagnosed with adhesive capsulitis and received additional treatment. Since no previous reports have presented a case of adhesive capsulitis after the reconstruction of bilateral axillary EMPD using skin graft, this case is noteworthy. [ABSTRACT FROM AUTHOR]

A genetically manipulable recombinant charybdotoxin (CTX) was used to investigate electrostatic interactions between CTX and a Ca2+ activated K+ channel. The small effects on the binding affinity of the toxin molecule were revealed by point mutations at certain charged residues. It seemed as though close-range interactions between the toxins and the receptor site of the channel appeared to be disrupted, because a large increase of toxin rate was noticed, but there was little effect on association rates. A molecular surface of CTX that makes direct contact with the extracellular mouth of the K+ channel, was revealed by mutation and functional mapping of CTX.

Protein aggregation can induce explicit neurotoxic events that trigger a number of presently untreatable neurodegenerative disorders. Chaperones, on the other hand, play a neuroprotective role because of their ability to unfold and refold abnormal proteins. The progressive nature of neurotoxic events makes it important to discover endogenous factors that affect pathologic and molecular phenotypes of neurodegeneration in animal models. Here, we identified microtubule-associated protein tau, and chaperones Hsp70 (heat shock protein 70) and DNAJA1 (DJ2) as endogenous substrates of cereblon (CRBN), a substrate-recruiting subunit of cullin4-RING-E3-ligase. This recruitment results in ubiquitin-mediated degradation of tau, Hsp70, and DJ2. Knocking out CRBN enhances the chaperone activity of DJ2, resulting in decreased phosphorylation and aggregation of tau, improved association of tau with microtubules, and reduced accumulation of pathologic tau across brain. Functionally abundant DJ2 could prevent tau aggregation induced by various factors like okadaic acid and heparin. Depletion of CRBN also decreases the activity of tau-kinases including GSK3a/b, ERK, and p38. Intriguingly, we found a high expression of CRBN and low levels of DJ2 in neuronal tissues of 5XFAD and APP knock-in male mouse models of Alzheimer's disease. This implies that CRBN-mediated DJ2/Hsp70 pathway may be compromised in neurodegeneration. Being one of the primary pathogenic events, elevated CRBN can be a contributing factor for tauopathies. Our data provide a functional link between CRBN and DJ2/Hsp70 chaperone machinery in abolishing the cytotoxicity of aggregation-prone tau and suggest that Crbn2/2 mice serve as an animal model of resistance against tauopathies for further exploration of the molecular mechanisms of neurodegeneration. [ABSTRACT FROM AUTHOR]

The novel artificial ion channels based on CB[n] (n = 6 and 5) transport proton and alkali metal ions across a lipid membrane with ion selectivity. The novel ion channel system could be useful in applications such as drug discovery, detection of small molecules, ion separation, and construction of molecular devices.

Background: T cell immunophenotypes in patients with hemophagocytic lymphohistiocytosis (HLH) have been described. Downregulation of CD5 or CD7 on T cells has been reported in patients with Epstein-Barr virus (EBV)-positive HLH. As the utility of T cell immunophenotypes as an adjunctive diagnostic or a prognostic marker for HLH has not been evaluated, we analyzed T cell immunophenotypes in HLH patients for this purpose. Methods: We classified 45 HLH patients into three subgroups: EBV-positive HLH (N=27), EBV-negative secondary HLH (N=15), and familial HLH (N=3). We retrospectively characterized downregulation patterns of CD5 or CD7 on activated T cells, using flow cytometry. Overall survival was estimated using Kaplan-Meier curves and compared using the log-rank test. Results: An aberrant immunophenotype, including CD5 and/or CD7 downregulation on T cells, was observed in 55.6% (15/27) of the EBV-positive HLH patients and 100% of the familial HLH (3/3). Only one (1/15, 6.7%) patient with EBV-negative secondary HLH showed an aberrant loss of CD7 antigen on CD8+ T cells. The presence of an aberrant T cell immunophenotype was not related to overall survival in EBV-positive HLH and EBV-negative secondary HLH patients. Conclusions: An aberrant T cell immunophenotype may assist in discriminating EBV-negative secondary HLH and EBV-positive HLH. However, it may not be useful as a prognostic marker. [ABSTRACT FROM AUTHOR]

In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12–99) with positive IGRA results. [ABSTRACT FROM AUTHOR]

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of a rapid antimicrobial susceptibility testing (AST) platform based on microfluidic chip technology, the QMAC-dRAST, which enables AST from colony isolates or positive blood culture broth (PBCB), and to compare the performance of the QMAC-dRAST for staphylococci and enterococci with that of the VITEK-2 system based on reference broth microdilution (BMD).Methods: A total of 110 staphylococcal and enterococcal isolates from blood cultures were included. AST was performed directly using the QMAC-dRAST with PBCB. Thereafter, colony isolates derived from subculture of PBCB were used for the QMAC-dRAST, the VITEK-2 system and BMD.Results: The overall agreement between the QMAC-dRAST with PBCB and BMD was 91.5%. There were 1.2% very major errors (VMEs), 4.3% major errors (MEs) and 5.4% minor errors (mEs). The QMAC-dRAST with colony isolates yielded 94.6% agreement and error rates of 1.0% VMEs, 1.8% MEs and 4.0% mEs. The VITEK-2 system showed 96.2% agreement and error rates of 2.3% VMEs, 0.5% MEs and 2.6% mEs. The incubation time in the QMAC-dRAST was significantly shorter than in the VITEK-2 system (median of 6 versus 10 h; P < 0.0001).Conclusions: The QMAC-dRAST system provided rapid results and represents an alternative to conventional AST methods. The QMAC-dRAST with colony isolates produced more reliable results for staphylococci and enterococci than the QMAC-dRAST with PBCB. The QMAC-dRAST system also performed comparably to BMD and the VITEK-2 system. [ABSTRACT FROM AUTHOR]

Mutations in the cereblon (CRBN) gene cause human intellectual disability, one of the most common cognitive disorders. However, the molecular mechanisms of CRBN-related intellectual disability remain poorly understood. We investigated the role of CRBN in synaptic function and animal behavior using male mouse and Drosophila models. Crbn knock-out (KO) mice showed normal brain and spine morphology as well as intact synaptic plasticity; however, they also exhibited decreases in synaptic transmission and presynaptic release probability exclusively in excitatory synapses. Presynaptic function was impaired not only by loss of CRBN expression, but also by expression of pathogenic CRBN mutants (human R419X mutant and Drosophila G552X mutant). We found that the BK channel blockers paxilline and iberiotoxin reversed this decrease in presynaptic release probability in Crbn KO mice. In addition, paxilline treatment also restored normal cognitive behavior in Crbn KO mice. These results strongly suggest that increased BK channel activity is the pathological mechanism of intellectual disability in CRBN mutations. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effects of pre-anesthetic administration of dexmedetomidine on sedative, cardiovascular, and recovery parameters. Methods: This was a prospective, randomized, double-blind, placebo-controlled study. We selected 60 patients who were scheduled to undergo laparoscopic cholecystectomy. They were randomly divided into two groups and received 0.5 mg/kg of dexmedetomidine (group D) or normal saline (group S) over 10 minutes before induction of anesthesia. The Ramsay sedation scale (RSS) score and bispectral index (BIS) were recorded after completion of the dexmedetomidine infusion. Mean arterial pressure (MAP), heart rate (HR), peripheral pulse oximetry, cardiac output (CO), and systemic vascular resistance (SVR) were recorded. The modified Aldrete recovery score (MARS) was recorded in the recovery room. Results: After completion of the dexmedetomidine infusion, BIS reduction was less than 20% (97.1 ± 2.4, 83.8 ± 4.8; P < 0.001), but RSS-rated sedation was appropriate (P < 0.001). HR was lowest at the end of the dexmedetomidine infusion and there was a significant difference between groups (P < 0.001); however, MAP was not significantly different between groups (P = 0.139). CO was lowest and SVR was highest at the end of the dexmedetomidine infusion. There was no significant difference in MARS values between groups (P = 0.190). Conclusions: A pre-anesthetic dexmedetomidine (0.5 mg/kg) provided appropriate sedation without serious changes in cardiovascular parameters or a prolonged recovery time. [ABSTRACT FROM AUTHOR]

Shear connectors are used in steel beam-concrete slabs of composite frame and bridge structures to transfer shear force according to design loads. The existing Y-type perfobond rib shear connectors are designed for girder slabs of composite bridges. Therefore, the rib and transverse rebars of the conventional Y-type perfobond rib shear connectors are extremely large for the composite frames of building structures. Thus, this paper proposes stubby Y-type perfobond rib shear connectors, redefining the existing connectors, for composite frames of building structures; these were used to perform push-out tests. These shear connectors have relatively small ribs compared to the conventional Y-type perfobond rib shear connectors. To confirm the shear resistance of these stubby shear connectors, we performed an experiment by using transverse rebars D13 and D16. The results indicate that these shear connectors have suitable shear strength and ductility for application in composite frame structures. The shear strengths obtained using D13 and D16 were not significantly different. However, the ductility of the shear connectors with D16 was 45.1% higher than that of the shear connectors with D13. [ABSTRACT FROM AUTHOR]

The importance of actin-binding proteins (ABPs) in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90), an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO) mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD), leaving basal synaptic transmission and long-term potentiation (LTP) intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD) 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3β signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility. [ABSTRACT FROM AUTHOR]

Panax ginseng C.A. Meyer is a traditional medicinal herb that produces bioactive compounds such as ginsenosides. Here, we investigated the diversity of ginsenosides and related genes among five genetically fixed inbred ginseng cultivars (Chunpoong [CP], Cheongsun [CS], Gopoong [GO], Sunhyang [SH], and Sunun [SU]). To focus on the genetic diversity related to ginsenoside biosynthesis, we utilized in vitro cultured adventitious roots from the five cultivars grown under controlled environmental conditions. PCA loading plots based on secondary metabolite composition classified the five cultivars into three groups.We selected three cultivars (CS, SH, and SU) to represent the three groups and conducted further transcriptome and gas chromatographymass spectrometry analyses to identify genes and intermediates corresponding to the variation in ginsenosides among cultivars. We quantified ginsenoside contents from the three cultivars. SH had more than 12 times the total ginsenoside content of CS, with especially large differences in the levels of panaxadiol-type ginsenosides. The expression levels of genes encoding squalene epoxidase (SQE) and dammarenediol synthase (DDS) were also significantly lower in CS than SH and SU, which is consistent with the low levels of ginsenoside produced in this cultivar. Methyl jasmonate (MeJA) treatment increased the levels of panaxadiol-type ginsenosides up to 4-, 13-, and 31- fold in SH, SU, and CS, respectively. MeJA treatment also greatly increased the quantity of major intermediates and the expression of the underlying genes in the ginsenoside biosynthesis pathway; these intermediates included squalene, 2,3-oxidosqualene, and dammarenediol II, especially in CS, which had the lowest ginsenoside content under normal culture conditions. We conclude that SQE and DDS are the most important genetic factors for ginsenoside biosynthesis with diversity among ginseng cultivars. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in themodern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of b-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized. [ABSTRACT FROM AUTHOR]

Nationalist historiography has ben the dominant historical perspective since the emergence of modern Korean historiography at the end of the 19th century. Nationalism has been very influential, but there has also been continuous criticism of the nationalist historical perspective from academics both inside and outside Korea. Postmodern historiography is beginning to become established among Korean historians, as reflected in the growth of microlevel research into the life history of the people.

Autologous adipose stromal vascular fractions (SVFs) containing adipose tissue-derived stem cells (ASCs) are currently being used in clinical settings for various orthopedic applications for human patients. Due to its potential capability of regenerating cartilage, bone, and tendons, autologous adipose SVFs are being tried in treating patients with osteoarthritis (OA), chondromalacia, meniscus tear, osteonecrosis of the femoral head, and tendon injuries. Here, we have reviewed available human clinical studies with regard to patient applications of autologous adipose SVF containing ASCs, specifically assessing effectiveness and safety in the field of orthopedic disorders. All studies reviewed in this article presents potential benefits of autologous adipose SVF in various orthopedic applications without any serious side effects. [ABSTRACT FROM AUTHOR]

During brain development, dynamic changes in neuronal membr anesper form critical roles in neuronal morphogenes is and migration to create functional neural circuits. Amongthe proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration andinducedmultiplebranchesinleadingprocessesduringcorticogenesis. These results indicate thatVstm5isanewcell-adhesion-likemolecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics. [ABSTRACT FROM AUTHOR]

The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4+ T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4+ T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4+ T-cell activation via epigenetic regulation of Kv1.3 expression. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM). The prevalence of gastroesophageal reflux disease (GERD) in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy) of GERD in patients with T2DM. Methods: This cross-sectional case-control study enrolled T2DM patients (n = 258) and healthy controls (n=184). All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA) classification was used to grade GERD. GERD was defined as LA grade A (or higher) or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups. Results: The prevalence of GERD (32.6% vs. 35.9%, P=0.266) and GERD symptoms (58.8% vs. 59.2%, P=0.503) was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control. Conclusion: The prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM. [ABSTRACT FROM AUTHOR]

The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase- 48 (OXA-48) type have been reported worldwide. New Delhi metallo-b-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemaseproducing K. pneumoniae are often resistant to most b-lactam antibiotics and many other non-b-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed. [ABSTRACT FROM AUTHOR]