Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Unbalanced fronto-pallidal neurocircuit underlying set shifting in obsessive-compulsive disorder.

Maladaptive habitual behaviours of obsessive-compulsive disorder are characterized by cognitive inflexibility, which hypothetically arises from dysfunctions of a certain cortico-basal ganglia-thalamo-cortical circuit including the ventrolateral prefrontal region. Inside this neurocircuit, an imbalance between distinct striatal projections to basal ganglia output nuclei, either directly or indirectly via the external globus pallidus, is suggested to be relevant for impaired arbitration between facilitation and inhibition of cortically initiated activity. However, current evidence of individually altered cortico-striatal or thalamo-cortical connectivities is insufficient to understand how cortical dysconnections are linked to the imbalanced basal ganglia system in patients. In this study, we aimed to identify aberrant ventrolateral prefronto-basal ganglia-thalamic subnetworks representing direct-indirect imbalance and its association with cognitive inflexibility in patients. To increase network detection sensitivity, we constructed a cortico-basal ganglia-thalamo-cortical network model incorporating striatal, pallidal and thalamic subregions defined by unsupervised clustering in 105 medication-free patients with obsessive-compulsive disorder (age = 25.05 ± 6.55 years, male/female = 70/35) and 99 healthy controls (age = 23.93 ± 5.80 years, male/female = 64/35). By using the network-based statistic method, we analysed group differences in subnetworks formed by suprathreshold dysconnectivities. Using linear regression models, we tested subnetwork dysconnectivity effects on symptom severity and set-shifting performance assessed by well-validated clinical and cognitive tests. Compared with the healthy controls, patients were slower to track the Part B sequence of the Trail Making Test when the effects of psychomotor and visuospatial functions were adjusted (t = 3.89, P < 0.001) and made more extradimensional shift errors (t = 4.09, P < 0.001). In addition to reduced fronto-striatal and striato-external pallidal connectivities and hypoconnected striato-thalamic subnetwork [P = 0.001, family-wise error rate (FWER) corrected], patients had hyperconnected fronto-external pallidal (P = 0.012, FWER corrected) and intra-thalamic (P = 0.015, FWER corrected) subnetworks compared with the healthy controls. Among the patients, the fronto-pallidal subnetwork alteration, especially ventrolateral prefronto-external globus pallidal hyperconnectivity, was associated with relatively fewer extradimensional shifting errors (ß = -0.30, P = 0.001). Our findings suggest that the hyperconnected fronto-external pallidal subnetwork may have an opposite effect to the imbalance caused by the reduced indirect pathway (fronto-striato-external pallidal) connectivities in patients. This ventrolateral prefrontal hyperconnectivity may help the external globus pallidus disinhibit basal ganglia output nuclei, which results in behavioural inhibition, so as to compensate for the impaired set shifting. We suggest the ventrolateral prefrontal and external globus pallidus as neuromodulatory targets for inflexible habitual behaviours in obsessive-compulsive disorder.

A Study on Wheel Member Condition Recognition Using 1D-CNN.

The condition of a railway vehicle's wheels is an essential factor for safe operation. However, the current inspection of railway vehicle wheels is limited to periodic major and minor maintenance, where physical anomalies such as vibrations and noise are visually checked by maintenance personnel and addressed after detection. As a result, there is a need for predictive technology concerning wheel conditions to prevent railway vehicle damage and potential accidents due to wheel defects. Insufficient predictive technology for railway vehicle's wheel conditions forms the background for this study. In this research, a real-time tire wear classification system for light-rail rubber tires was proposed to reduce operational costs, enhance safety, and prevent service delays. To perform real-time condition classification of rubber tires, operational data from railway vehicles, including temperature, pressure, and acceleration, were collected. These data were processed and analyzed to generate training data. A 1D-CNN model was employed to classify tire conditions, and it demonstrated exceptionally high performance with a 99.4% accuracy rate.

A Study on Wheel Member Condition Recognition Using Machine Learning (Support Vector Machine).

The wheels of railway vehicles are of paramount importance in relation to railroad operations and safety. Currently, the management of railway vehicle wheels is restricted to post-event inspections of the wheels whenever physical phenomena, such as abnormal vibrations and noise, occur during the operation of railway vehicles. To address this issue, this paper proposes a method for predicting abnormalities in railway wheels in advance and enhancing the learning and prediction performance of machine learning algorithms. Data were collected during the operation of Line 4 of the Busan Metro in South Korea by directly attaching sensors to the railway vehicles. Through the analysis of key factors in the collected data, factors that can be used for tire condition classification were derived. Additionally, through data distribution analysis and correlation analysis, factors for classifying tire conditions were identified. As a result, it was determined that the z-axis of acceleration has a significant impact, and machine learning techniques such as SVM (Linear Kernel, RBF Kernel) and Random Forest were utilized based on acceleration data to classify tire conditions into in-service and defective states. The SVM (Linear Kernel) yielded the highest recognition rate at 98.70%.

Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy.

PURPOSE: The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer. METHODS: We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea. RESULTS: The 786 patients in the pathologic complete response group (RpCR) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R0) and the 68 patients in involved RM and non-pCR group (R1) (vs. R0, p = 0.001; vs. R1, p = 0.049). Patients in R0 showed no benefit in LRFS compared to R1 on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R0 and R1 group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS. CONCLUSION: Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Metabotropic Glutamate Receptor 5 in Natural Killer Cells Attenuates Liver Fibrosis by Exerting Cytotoxicity to Activated Stellate Cells.

BACKGROUND AND AIMS: The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon-γ (IFN-γ) production in both mice and humans. APPROACH AND RESULTS: Following 2-week injection of carbon tetrachloride (CCl4 ) or 5-week methionine-deficient and choline-deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild-type mice. Consistently, NK cell-specific mGluR5 knockout mice had aggravated CCl4 -induced liver fibrosis with decreased production of IFN-γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti-fibrosis-related genes including Ifng, Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN-γ through the mitogen-activated extracellular signal-regulated kinase/extracellular signal-related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo, pharmacologic activation of mGluR5 accelerated CCl4 -induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells. CONCLUSIONS: mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.

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

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

High-Field Magnetoelectric and Spin-Phonon Coupling in Multiferroic (NH4)2[FeCl5·(H2O)].

We combine high field polarization, magneto-infrared spectroscopy, and lattice dynamics calculations with prior magnetization to explore the properties of (NH4)2[FeCl5·(H2O)]─a type II molecular multiferroic in which the mixing between charge, structure, and magnetism is controlled by intermolecular hydrogen and halogen bonds. Electric polarization is sensitive to the series of field-induced spin reorientations, increasing linearly with the field and reaching a maximum before collapsing to zero across the quasi-collinear to collinear-sinusoidal reorientation due to the restoration of inversion symmetry. Magnetoelectric coupling is on the order of 1.2 ps/m for the P∥c, H∥c configuration between 5 and 25 T at 1.5 K. In this range, the coupling takes place via an orbital hybridization mechanism. Other forms of mixing are active in (NH4)2[FeCl5·(H2O)] as well. Magneto-infrared spectroscopy reveals that all of the vibrational modes below 600 cm-1 are sensitive to the field-induced transition to the fully saturated magnetic state at 30 T. We analyze these local lattice distortions and use frequency shifts to extract spin-phonon coupling constants for the Fe-O stretch, Fe-OH2 rock, and NH4+ libration. Inspection also reveals subtle symmetry breaking of the ammonium counterions across the ferroelectric transition. The coexistence of such varied mixing processes in a platform with intermolecular hydrogen- and halogen-bonding opens the door to greater understanding of multiferroics and magnetoelectrics governed by through-space interactions.

A Direct Feedback FVF LDO for High Precision FMCW Radar Sensors in 65-nm CMOS Technology.

A direct feedback flipped voltage follower (FVF) LDO for a high-precision frequency-modulated continuous-wave (FMCW) radar is presented. To minimize the effect of the power supply ripple on the FMCW radar sensor's resolution, a folded cascode error amplifier (EA) was connected to the outer loop of the FVF to increase the open-loop gain. The direct feedback structure enhances the PSRR while minimizing the power supply ripple path and not compromising a transient response. The flipped voltage follower with a super source follower forms a fast feedback loop. The stability and parameter variation sensitivity of the multi-loop FVF LDO were analyzed through the state matrix decomposition. We implemented the FVF LDO in TSMC 65 nm CMOS technology. The fabricated FVF LDO supplied a maximum load current of 20 mA with a 1.2 V power supply. The proposed FVF LDO achieved a full-spectrum PSR with a low-frequency PSRR of 66 dB, unity-gain bandwidth of 469 MHz, and 20 ns transient settling time with a load current step from 1 mA to 20 mA.

EmbeddedPigCount: Pig Counting with Video Object Detection and Tracking on an Embedded Board.

Knowing the number of pigs on a large-scale pig farm is an important issue for efficient farm management. However, counting the number of pigs accurately is difficult for humans because pigs do not obediently stop or slow down for counting. In this study, we propose a camera-based automatic method to count the number of pigs passing through a counting zone. That is, using a camera in a hallway, our deep-learning-based video object detection and tracking method analyzes video streams and counts the number of pigs passing through the counting zone. Furthermore, to execute the counting method in real time on a low-cost embedded board, we consider the tradeoff between accuracy and execution time, which has not yet been reported for pig counting. Our experimental results on an NVIDIA Jetson Nano embedded board show that this "light-weight" method is effective for counting the passing-through pigs, in terms of both accuracy (i.e., 99.44%) and execution time (i.e., real-time execution), even when some pigs pass through the counting zone back and forth.

Anti-Cancer Effects of a New Herbal Medicine PSY by Inhibiting the STAT3 Signaling Pathway in Colorectal Cancer Cells and Its Phytochemical Analysis.

Colorectal cancer (CRC) is an inflammation-associated common cancer worldwide. Paejang-san and Mori Cortex Radicis have been traditionally used for treating intestinal inflammatory diseases in Korea and China. In the present study, we developed a new herbal formula as an alternative to CRC treatments, which is composed of two main components of Paejangsan (Patriniae Radix (Paejang in Korean) and Coix Seed (Yiyiin in Korean)), and Mori Cortex Radicis (Sangbekpi in Korean) based on the addition and subtraction theory in traditional medicine, hence the name PSY, and explored the potential therapeutic effects of the new formula PSY in human CRC cells by analyzing viability, cell cycle and apoptosis. We found that PSY ethanol extract (EtOH-Ex), but not water extract, significantly suppressed the viability of human CRC cells, and synergistically decreased the cell proliferation compared to each treatment of Patriniae Radix and Coix Seed extract (PY) or Mori Cortex Radicis extract (S), suggesting the combination of PY and S in a 10-to-3 ratio for the formula PSY. PSY EtOH-Ex in the combination ratio reduced cell viability but induced cell cycle arrest at the G2/M and sub-G1 phases as well as apoptosis in CRC cells. In addition, the experimental results of Western blotting, immunofluorescence staining and reporter assays showed that PSY also inhibited STAT3 by reducing its phosphorylation and nuclear localization, which resulted in lowering STAT3-mediated transcriptional activation. In addition, PSY regulated upstream signaling molecules of STAT3 by inactivating JAK2 and Src and increasing SHP1. Moreover, the chemical profiles of PSY from UPLC-ESI-QTOF MS/MS analysis revealed 38 phytochemicals, including seven organic acids, eight iridoids, two lignans, twelve prenylflavonoids, eight fatty acids, and one carbohydrate. Furthermore, 21 potentially bioactive compounds were highly enriched in the PSY EtOH-Ex compared to the water extract. Together, these results indicate that PSY suppresses the proliferation of CRC cells by inhibiting the STAT3 signaling pathway, suggesting PSY as a potential therapeutic agent for treating CRC and 21 EtOH-Ex-enriched phytochemicals as anti-cancer drug candidates which may act by inhibiting STAT3.

Ginkgolide C promotes apoptosis and abrogates metastasis of colorectal carcinoma cells by targeting Wnt/ß-catenin signaling pathway.

Ginkgolide C (GGC), isolated from Ginkbiloba, has been reported to display various pharmacological actions, although, anti-cancer effect of GGC has been poorly understood till now. This study aimed to investigate whether GGC can exhibit anti-neoplastic effects against colon cancer cells and explore underlying mechanism. The Wnt/ß-catenin signaling can regulate cell proliferation, survival, metastasis, and migration. Wnt/ß-catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Abnormal activation of this signaling cascades has been reported in colon CRC. We found that GGC down-regulated Wnt/ß-catenin signaling cascade. GGC inhibited the expression of Wnt3a, ß-catenin, and ß-catenin down-stream signals (Axin-1, p-GSK3ß, and ß-TrCP). Also, GGC suppressed the expression of Wnt/ß-catenin pathway target genes including c-myc, cyclin D1, and survivin. Additionally, GGC induced apoptosis and suppressed cell proliferation, invasion, and migration. GGC down-regulated the expressions of matrix metalloproteinase (MMP)-9 and MMP-2 proteins. Moreover, silencing of ß-catenin by small interfering RNA (siRNA) enhanced the GGC-induced apoptosis and inhibitory action of GGC on invasion. Overall, our results indicate that GGC can reduce proliferation and promote apoptosis in colon cancer cells through inhibition of the Wnt/ß-catenin signaling pathway. Thus, GGC can serve as a potent therapeutic agent for management of colon cancer as a novel wnt signaling inhibitor.

Mitochondrial Double-Stranded RNA in Exosome Promotes Interleukin-17 Production Through Toll-Like Receptor 3 in Alcohol-associated Liver Injury.

BACKGROUND AND AIMS: Mitochondrial double-stranded RNA (mtdsRNA) and its innate immune responses have been reported previously; however, mtdsRNA generation and its effects on alcohol-associated liver disease (ALD) remain unclear. Here, we report that hepatic mtdsRNA stimulates toll-like receptor 3 (TLR3) in Kupffer cells through the exosome (Exo) to enhance interleukin (IL)-17A (IL-17A) production in ALD. APPROACH AND RESULTS: Following binge ethanol (EtOH) drinking, IL-17A production primarily increased in γδ T cells of wild-type (WT) mice, whereas the production of IL-17A was mainly facilitated by CD4+ T cells in acute-on-chronic EtOH consumption. These were not observed in TLR3 knockout (KO) or Kupffer cell-depleted WT mice. The expression of polynucleotide phosphorylase, an mtdsRNA-restricting enzyme, was significantly decreased in EtOH-exposed livers and hepatocytes of WT mice. Immunostaining revealed that mtdsRNA colocalized with the mitochondria in EtOH-treated hepatocytes from WT mice and healthy humans. Bioanalyzer analysis revealed that small-sized RNAs were enriched in EtOH-treated Exos (EtOH-Exos) rather than EtOH-treated microvesicles in hepatocytes of WT mice and humans. Quantitative real-time PCR and RNA sequencing analyses indicated that mRNA expression of mitochondrial genes encoded by heavy and light strands was robustly increased in EtOH-Exos from mice and humans. After direct treatment with EtOH-Exos, IL-1ß expression was significantly increased in WT Kupffer cells but not in TLR3 KO Kupffer cells, augmenting IL-17A production of γδ T cells in mice and humans. CONCLUSIONS: EtOH-mediated generation of mtdsRNA contributes to TLR3 activation in Kupffer cells through exosomal delivery. Consequently, increased IL-1ß expression in Kupffer cells triggers IL-17A production in γδ T cells at the early stage that may accelerate IL-17A expression in CD4+ T cells in the later stage of ALD. Therefore, mtdsRNA and TLR3 may function as therapeutic targets in ALD.

Distinct neural networks associated with obsession and delusion: a connectome-wide association study.

BACKGROUND: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS). METHODS: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression. RESULTS: Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network. CONCLUSIONS: Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

In vivo gamma-aminobutyric acid-A/benzodiazepine receptor availability and genetic liability in asymptomatic individuals with high genetic loading of schizophrenia: A [11C]flumazenil positron emission tomography study.

OBJECTIVES: Whilst reduced signalling and gene expression related to gamma-aminobutyric acid (GABA) play a role in the presumed pathophysiology of schizophrenia, its origin is unclear. Studying asymptomatic individuals with high genetic liability to schizophrenia (AIs) would provide insights. Therefore, this study aimed to investigate the role of genetic liability in GABAergic dysfunction of schizophrenia by exploring in vivo GABA-A/benzodiazepine receptor (GABAR) availability in AIs. METHODS: A total of 10 AIs with multiple relatives diagnosed as schizophrenia and 11 healthy controls underwent [11C]flumazenil positron emission tomography and neurocognitive function tests. RESULTS: There was no significant difference in [11C]flumazenil availability based on the groups. GABAR availability in caudate nuclei had positive correlations with genetic liability of AIs. GABAR availability in caudate nuclei and verbal memory measures of AIs revealed positive correlations. Only the correlation between right caudate and short-term verbal memory survived multiple-comparison correction (p = 0.030). CONCLUSIONS: This study, for the first time, reports correlations between the genetic liability of schizophrenia and GABAR availability. Correlations between [11C]flumazenil binding in caudate of individuals with high genetic liability to schizophrenia suggests that the GABAergic dysfunction may arise from shared genetic factors and also that it may be responsible for cognitive impairment of AIs.

Review of Capacitive Touchscreen Technologies: Overview, Research Trends, and Machine Learning Approaches.

Touchscreens have been studied and developed for a long time to provide user-friendly and intuitive interfaces on displays. This paper describes the touchscreen technologies in four categories of resistive, capacitive, acoustic wave, and optical methods. Then, it addresses the main studies of SNR improvement and stylus support on the capacitive touchscreens that have been widely adopted in most consumer electronics such as smartphones, tablet PCs, and notebook PCs. In addition, the machine learning approaches for capacitive touchscreens are explained in four applications of user identification/authentication, gesture detection, accuracy improvement, and input discrimination.

DG-LoRa: Deterministic Group Acknowledgment Transmissions in LoRa Networks for Industrial IoT Applications.

In this paper, we propose a novel MAC protocol, called DG-LoRa, for improving scalability in low power wide area networks. DG-LoRa is backward compatible with legacy LoRaWAN and adds new features, such as group acknowledgment transmissions in the time-synchronized frame structure that supports determinism on channel access. In DG-LoRa, the number of responses to data frames that are transmitted from end devices is maximized by allocating the spreading factor and timeslot in the frame structure. We evaluate the performance of DG-LoRa using the Monte-Carlo simulation and then compare it with the performance of legacy LoRaWAN in terms of data drop rate and the number of retransmissions. Our numerical results show that DG-LoRa supports approximately five times more connections to the LoRa network satisfying a 5% data drop rate. Also, it is observed that DG-LoRa enables low overhead by reducing the number of data frame retransmissions.

Pyrimethamine Modulates Interplay between Apoptosis and Autophagy in Chronic Myelogenous Leukemia Cells.

Pyrimethamine (Pyri) is being used in combination with other medications to treat serious parasitic infections of the body, brain, or eye and to also reduce toxoplasmosis infection in the patients with HIV infection. Additionally, Pyri can display significant anti-cancer potential in different tumor models, but the possible mode of its actions remains unclear. Hence, in this study, the possible anti-tumoral impact of Pyri on human chronic myeloid leukemia (CML) was deciphered. Pyri inhibited cell growth in various types of tumor cells and exhibited a marked inhibitory action on CML cells. In addition to apoptosis, Pyri also triggered sustained autophagy. Targeted inhibition of autophagy sensitized the tumor cells to Pyri-induced apoptotic cell death. Moreover, the activation of signal transducer and activator of transcription 5 (STAT5) and its downstream target gene Bcl-2 was attenuated by Pyri. Accordingly, small interfering RNA (siRNA)-mediated STAT5 knockdown augmented Pyri-induced autophagy and apoptosis and promoted the suppressive action of Pyri on cell viability. Moreover, ectopic overexpression of Bcl-2 protected the cells from Pyri-mediated autophagy and apoptosis. Overall, the data indicated that the attenuation of STAT5-Bcl-2 cascade by Pyri can regulate its growth inhibitory properties by simultaneously targeting both apoptosis and autophagy cell death mechanism(s).

A Prospective Study for Prediction of Psychotic Relapse Using the Korean Early Signs Scale in Patients With Schizophrenia.

INTRODUCTION: A psychotic relapse of schizophrenia is commonly preceded by nonpsychotic behavioral symptoms and signs, and detection of these early signs may enable prevention of relapse of schizophrenia. This study aimed to test the predictive validity of a Korean version of Early Signs Scale (K-ESS) for psychotic relapse for detecting the early signs. MATERIALS AND METHODS: In this multicenter noninterventional 52-week prospective study, outpatients diagnosed as having schizophrenia within 5 years were recruited. The K-ESS and Clinical Global Impression-Severity (CGI-S) scale were administered monthly until the end of the study or the relapse. The primary objective was to determine an optimal cutoff point of K-ESS score for prediction of psychotic relapse. The secondary objective was to assess the concurrent validity of the K-ESS using CGI-S scale. RESULTS: Among the 162 included patients, 14 (8.6%) relapsed during the 52-week study period. The optimal cutoff score of K-ESS was 15 with a sensitivity of 71.43% and a specificity of 52.70%, indicating poor predictive accuracy of K-ESS. A lower cutoff K-ESS score of 3 and a higher cutoff score of 28 were found in the subgroups with milder (CGI-S = 1-2) and severer (CGI-S = 3-4) symptom severity, respectively, with fair to good predictive accuracy. The K-ESS showed acceptable concurrent validity with CGI-S and concordance rate between self-rated and informant-rated scores. DISCUSSION: The predictive accuracy of K-ESS was limited by evaluation interval of a month. At least fortnightly follow-up would be needed for detection of early signs to prevent a psychotic relapse in schizophrenia.

Neural bases of the clinical and neurocognitive differences between earlyand late-onset obsessive­compulsive disorder

Background: Using biological evidence to define subtypes within the heterogeneous population with obsessive­compulsive disorder (OCD) is important for improving treatment response. Based on age at onset, OCD can be clustered into 2 groups, each of which is more homogeneous with respect to clinical and cognitive phenotype. However, the neural bases for these phenotypic differences need to be established to construct evidence-based homogeneous groups. Methods: We compared brain volumes, clinical symptoms, and neurocognitive function for 49 people with early-onset OCD and 52 with late-onset OCD (participants in both groups were unmedicated or drug-naïve), and 103 healthy controls. We performed regression analyses to examine group × volume interaction effects on clinical outcomes or neurocognitive function in people with OCD. Results: We observed larger volumes in the precentral, orbitofrontal, middle frontal, and middle temporal gyri in people with early-onset OCD compared to those with late-onset OCD. Poorer visuospatial construction in early-onset OCD was correlated with a larger left middle frontal gyrus volume. Impaired visuospatial memory in people with early-onset OCD and cognitive inflexibility in people with late-onset OCD were correlated with increased and decreased volume in the left middle frontal gyrus, respectively. We found group × volume interactions for obsessive­compulsive symptom scores in the left middle temporal gyrus of people with OCD. Limitations: Although we divided the subtypes using the commonly adopted criterion of age at onset, this criterion is still somewhat controversial. Conclusion: We provided the neural bases for clinical and neurocognitive differences to demonstrate that biological evidence underlies the distinctions between early- and late-onset OCD. This study suggests that different treatment options should be considered for the OCD subtypes, because their neurobiology differs and is related to distinct phenotypic profiles.