Metastable hexagonal close-packed palladium hydride in liquid cell TEM.

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

miRNA-independent function of long noncoding pri-miRNA loci.

Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1-independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.

Maladaptive neurovisceral interactions in patients with Internet gaming disorder: A study of heart rate variability and functional neural connectivity using the graph theory approach.

Heart rate variability (HRV) can be used to represent the regulatory adaptive system and is a proxy for neurovisceral integration. Consistent with the view that, like other addictions, Internet gaming disorder (IGD) involves disrupted regulatory function, the present study hypothesized that IGD patients would show (a) decreased HRV, (b) ineffective functional neural connectivity, and (c) differential patterns of association between HRV and functional neural connectivity relative to healthy controls (HCs). The present study included 111 young adults (53 IGD patients and 58 age- and sex-matched HCs) who underwent simultaneous recordings with an electrocardiogram and electroencephalogram during a resting state. Heart rate (HR), HRV, and functional neural connectivity were calculated using the graph theory approach. Compared with the HCs, the IGD patients exhibited elevated HR and decreased HRV based on the high frequency (HF), which reflects suppression of parasympathetic and/or vagal tone. The IGD patients also exhibited a heightened theta band characteristic path length (CPL) compared with HCs, indicating decreased efficacy of the functional network. Furthermore, IGD patients exhibited negative correlations between the standard deviation of the normal-to-normal interval index (SDNNi) and theta and delta CPL values, which were not observed in HCs. In conclusion, the present findings suggest that IGD patients might have maladaptive brain-body integration features involving disruptions of the autonomic nervous system and brain function.

Host plant growth promotion and cadmium detoxification in Solanum nigrum, mediated by endophytic fungi.

Current investigation conducted to evaluate the associated fungal endophyte interactions of a Cd hyper-accumulator Solanum nigrum Korean ecotype under varying concentrations of Cd. Two indole-3-acetic acid (IAA) producing fungal strains, RSF-4L and RSF-6L, isolated from the leaves of S. nigrum, were initially screened for Cd tolerance and accumulation potential. In terms of dry biomass production, the strain RSF-6L showed higher tolerance and accumulation capacity for Cd toxicity in comparison to RSF-4L. Therefore, RSF-6L was applied in vivo to S. nigrum and grown for six weeks under Cd concentrations of 0, 10, and 30mgKg-1 of dry sand. The effect of fungal inoculation assessed by plant physiological responses, endogenous biochemical regulations, and Cd profile in different tissues. Significant increase were observed in plant growth attributes such as shoot length, root length, dry biomass, leaf area, and chlorophyll contents in inoculated RSF-6L plants in comparison to non-inoculated plants with or without Cd contamination. RSF-6L inoculation decreased uptake of Cd in roots and above ground parts, as evidenced by a low bio-concentration factor (BCF) and improved tolerance index (TI). However, Cd concentration in the leaves remained the same for inoculated and non-inoculated plants under Cd spiking. Fungal inoculation protected the host plants, as evidenced by low peroxidase (POD) and polyphenol peroxidase (PPO) activities and high catalase (CAT) activity. Application of appropriate fungal inoculation that can improve tolerance mechanisms of hyper-accumulators and reduce Cd uptake can be recommended for phyto-stabilisation/immobilisation of heavy metals in crop fields.

Range of S-100ß levels during functional endoscopic sinus surgery with moderately controlled hypotension.

The aim of this study is to determine the range of S-100ß levels during functional endoscopic sinus surgery (FESS) when the mean arterial pressure (MAP) was controlled within 60-70 mmHg. After anesthesia induction with propofol and remifentanil, the patient was positioned in the reverse Trendelenburg position and MAP was controlled within 60-70 mmHg during surgery. For the S-100ß assay, blood was taken from a radial arterial catheter before (baseline) and at 20 (T 20) and 60 (T 60) min after setting the reverse Trendelenburg position and controlled hypotension, and at 60 (T post60) min after the end of the operation. In total, 34 patients completed the study. Baseline S-100ß was 0.00837 ± 0.00785 ng/mL. The levels at T 20 and T 60 were 0.02057 ± 0.01739 and 0.01987 ± 0.01145 ng/mL, respectively. The level of T post60 was 0.05436 ± 0.02318 ng/mL. The level at T 20 increased significantly versus the baseline level (P < 0.001); there were no significant differences between T 20 and T 60. The level at T post60 was significantly different versus T 20 and T 60 (P < 0.001). However, all S-100ß levels were within the normal range. S-100ß-a sensitive biomarker of cerebral ischemia-was within the normal range during FESS when moderate hypotension (MAP >60 mmHg) was provided. Thus, moderate hypotension would be seemed to be a safe and effective anesthetic technique for FESS without risk for cerebral ischemia.

Inhibition of interleukin-1ß-mediated interleukin-1 receptor-associated kinase 4 phosphorylation by zinc leads to repression of memory T helper type 17 response in humans.

Zinc is an essential trace element that plays pivotal roles in multiple facets of the immune system. Besides its catalytic and structural roles, zinc also functions as an intracellular signalling molecule, and changes in zinc levels can cause both direct and indirect modulation of immune responses. Further, cytoplasmic levels of bioavailable zinc in immune cells are largely influenced by many extracellular stimuli. Here we provide evidence that zinc represses memory T helper type 17 responses in humans by inhibiting interleukin-1ß (IL-1ß)-mediated signal. In vitro zinc treatment of CD4(+) T cells in the presence of activated monocytes inhibited interferon-γ-producing cells and IL-17-producing cells, but not IL-4-producing cells. Of note, production of IL-17(+) cells from memory CD4(+) T cells, which is significantly up-regulated by lipopolysaccharide-stimulated monocytes, was preferentially repressed by zinc. Increased cytoplasmic zinc in T cells suppressed IL-1ß signalling through repression of phosphorylation of IL-1 receptor-associated kinase 4 (IRAK4), so leading to an inhibitory effect on T helper type 17 responses facilitated by monocyte-derived IL-1ß in humans. These findings suggest that extracellular zinc bioavailability may affect memory CD4(+) T-cell responses by modulating the zinc-mediated signalling pathway.

A novel mathematical model to predict the severity of postoperative functional reduction before partial nephrectomy: the importance of calculating resected and ischemic volume.

PURPOSE: Preoperatively predicting postoperative kidney function is an essential step to achieve improved renal function and prevent chronic kidney disease. We introduce a novel formula especially to calculate resected and ischemic volume before partial nephrectomy. We examined whether resected and ischemic volume would have value for predicting postoperative renal function. MATERIALS AND METHODS: We performed a retrospective cohort study in 210 patients who underwent robotic partial nephrectomy between September 2006 and October 2013 at a tertiary cancer care center. Based on abdominopelvic computerized tomography and magnetic resonance imaging we calculated resected and ischemic volume by the novel mathematical formula using integral calculus. We comparatively analyzed resected and ischemic volume, and current nephrometry systems to determine the degree of association and predictability regarding the severity of the postoperative functional reduction. RESULTS: On multivariable analysis resected and ischemic volume showed a superior association with the absolute change in estimated glomerular filtration rate/percent change in estimated glomerular filtration rate (B = 6.5, p = 0.005/B = 6.35, p = 0.009). The ROC AUC revealed accurate predictability of resected and ischemic volume on the stratified event of an absolute change in estimated glomerular filtration rate/event of percent change in estimated glomerular filtration rate compared to 3 representative nephrometry systems. The calibration plot of this model was excellent (close to the 45-degree line) within the whole range of predicted probabilities. CONCLUSIONS: We report a method of preoperatively calculating resected and ischemic volume with a novel formula. This method has superior correlation with the absolute and percent change in estimated glomerular filtration rate compared to current nephrometry systems. The predictive model achieved a strong correlation for the absolute and percent change in estimated glomerular filtration rate.

Clinical values of selective-clamp technique in robotic partial nephrectomy.

PURPOSE: In the era of robotic partial nephrectomy (RPN), several efforts on improved renal functional outcome have been reported. Selective-clamp is a novel technique that eliminates global ischemia, the clinical value of which needs to be demonstrated. The purpose of this study was to compare the postoperative functional outcomes of patients who underwent selective-clamp and total-clamping RPN. PATIENTS AND METHODS: From February 2009 to October 2012, a database of 126 consecutive patients who underwent RPN was retrospectively analyzed, 117 patients met our inclusion criteria and were stratified into two groups, 20 patients underwent selective-clamp RPN, and 97 patients underwent total-clamping RPN. Post hoc power analysis was subsequently performed for calculation of sufficient sample size. Demographics/tumor characteristics, functional outcomes and complications were analyzed. RESULTS: All selective-clamp RPN cases were successfully performed. Mean tumor size was 3.4 cm [standard deviation (SD): ±1.4], mean RENAL nephrometry score was 7.3 (SD: ±2.0), and no Clavien-Dindo III-V complications were recorded. Selective-clamp RPN group had a significantly lower percentage decrease in the postoperative estimated glomerular filtration rate at 1 week (1.8 vs. 20.8 ml/min/1.73 m(2), p = 0.001) and 3 months (0 vs. 9.9 ml/min/1.73 m(2), p = 0.032) when compared with the total-clamping RPN group. There were no significant differences in surgical margin and complication rates. CONCLUSIONS: Selective-clamp confers improved renal functional outcomes in comparison to total-clamping RPN, with acceptable complications and oncological outcomes even in large and complex tumors.

Identification of small molecule inhibitors of the STAT3 signaling pathway: Insights into their structural features and mode of action.

A series of novel STAT3 inhibitors consisting of Michael acceptor has been identified through assays of the focused in-house library. In addition, their mode of action and structural feature responsible for the STAT3 inhibition were investigated. In particular, analog 6 revealed promising STAT3 inhibitory activity in HeLa cell lines. The analog also exhibited selective inhibition of STAT3 phosphorylation without affecting STAT1 phosphorylation and cytostatic effect in human breast epithelial cells (MCF10A-ras), which supports cancer cell-specific inhibitory properties.

The efficacy of pre-warming on reducing intraprocedural hypothermia in endovascular coiling of cerebral aneurysms.

BACKGROUND: The anesthetic management of patients undergoing endovascular treatment of cerebral aneurysms in the interventional neuroradiology suite can be challenged by hypothermia because of low ambient temperature for operating and maintaining its equipments. We evaluated the efficacy of skin surface warming prior to induction of anesthesia to prevent the decrease in core temperature and reduce the incidence of hypothermia. METHODS: Seventy-two patients were randomized to pre-warmed and control group. The patients in pre-warmed group were warmed 30 minutes before induction with a forced-air warming blanket set at 38°C. Pre-induction tympanic temperature (Tpre) was measured using an infrared tympanic thermometer and core temperature was measured at the esophagus immediately after intubation (T0) and recorded at 20 minutes intervals (T20, T40, T60, T80, T100, and T120). The number of patients who became hypothermic at each time was recorded. RESULTS: Tpre in the control and pre-warmed group were 36.4 ± 0.4°C and 36.6 ± 0.3°C, whereas T0 were 36.5 ± 0.4°C and 36.6 ± 0.2°C. Core temperatures in the pre-warmed group were significantly higher than the control group at T20, T40, T60, T80, T100, and T120 (P < 0.001). Compared to T0, core temperatures at each time were significantly lower in both two groups (P = 0.007 at T20 in pre-warmed group, P < 0.001 at the other times in both groups). The incidence of hypothermia was significantly lower in the pre-warmed group than the control group from T20 to T120 (P = 0.002 at T20, P < 0.001 at the other times). CONCLUSION: Pre-warming for 30 minutes at 38°C did not modify the trends of the temperature decrease seen in the INR suite. It just slightly elevated the beginning post intubation base temperature. The rate of decrease was similar from T20 to T120. However, pre-warming considerably reduced the risk of intraprocedural hypothermia. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) Identifier: KCT0001320. Registered December 19th, 2014.

Plant growth-promoting potential of endophytic fungi isolated from Solanum nigrum leaves.

Fungal endophytes have been characterized as producers of phytohormones and potent promoters of plant growth. In this study, two fungal endophytes, Fusarium tricinctum RSF-4L and Alternaria alternata RSF-6L, were isolated from the leaves of Solanum nigrum. Culture filtrates (CFs) from each isolate were initially screened for indole compounds, and assayed for their ability to promote the growth of Dongjin rice plants. Nearly all plant growth attributes examined (i.e., chlorophyll content, root-shoot length, and biomass production) were significantly enhanced upon treatment with fungal CFs. Subsequently, gas chromatography/mass spectrometry analyses were utilized to confirm the presence of phytohormones in the CF of each fungal endophytic isolate. These analyses revealed that RSF-4L and RSF-6L produced 54 and 30 µg/mL indole acetic acid, respectively, within their respective cultures. These findings suggest that the endophytes isolated in this study synthesize bioactive compounds that could play important roles in promoting plant growth.

Laparoendoscopic single-site (LESS) robot-assisted partial nephrectomy (RAPN) reduces postoperative wound pain without a rise in complication rates.

OBJECTIVE: To compare long-term functional outcomes and pain scale scores of patients who underwent laparoendoscopic single-site (LESS)- robot-assisted partial nephrectomy (RAPN) to those who underwent conventional RAPN (C-RAPN), as LESS surgery is increasingly being adopted by urologists worldwide to reduce morbidities and scarring associated with surgical interventions. PATIENTS AND METHODS: In all, 167 consecutive patients who had RAPN were identified from our Institutional Review Board-approved computerised database between October 2006 to July 2012. Patients were stratified into two groups: 80 patients who underwent C-RAPN and 79 who underwent LESS-RAPN. RESULTS: The LESS-RAPN group had a longer warm ischaemia time [WIT, mean (sd) 26.5 (10.5) vs 19.8 (13.1) min; P = 0.001] and total operation time [TOT, mean (sd) 210.3 (83.4) vs 183.1 (76.1) min; P = 0.033] when compared with the C-RAPN group. While, the LESS-RAPN group and C-RAPN group were not significantly different for the number of patients with negative surgical margins [77 (96.2%) vs 73 (91.4%); P = 0.194), absolute change in postoperative renal function [mean (sd) -6.5 (16.7)% vs -7.6 (16.7)%; P = 0.738) and postoperative complications rate [12 (15.0%) vs 10 (12.6%); P = 0.279). Furthermore, the LESS-RAPN group had lower visual analogue pain scale (VAPS) scores at discharge [mean (sd) 2.1 (1.3) vs 1.7 (1.0); P = 0.048]. CONCLUSIONS: Despite a significantly longer WIT and TOT, the functional outcomes of LESS-RAPN were comparable to those of C-RAPN for tumours of similar mean sizes and complexities, without any detriments in oncological and complications outcomes. On discharge, patients who underwent LESS-RAPN also reported lower pain levels as one of the advantages of minimally invasive surgery. With the development of instrumentation specifically designed for single-site surgery, LESS could be more easily conducted in patients who are interested in improved quality of life outcomes.

Cloning, expression, and characterization of thermophilic L-asparaginase from Thermococcus kodakarensis KOD1.

The present study demonstrates cloning, expression, and characterization of hyperthermostable L-asparaginase from Thermococcus kodakarensis KOD1 in Escherichia coli BLR(DE3). The recombinant 6× His-tagged protein L-asparaginase from T. kodakarensis (TkAsn), was purified to homogeneity by heat treatment followed by affinity chromatography using a nickel-nitrilotriacetic acid (Ni-NTA) column. The molecular mass of the purified enzyme was found to be approximately 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzymatic properties, such as optimum temperature and pH, were 90 °C and 8.0, respectively. Its appearent Km , Vmax , and Kcat values were 2.6 mM, 1121 µmol min(-1) mg(-1) , and 694 S(-1) , respectively. The enzyme displayed high thermal stability at optimum temperature with an insignificant loss in enzymatic activity, retaining almost 90% of its activity over a time period of 32 h. The relative activity of the enzyme was significantly inhibited by the supplementation of Cu(2+) and Ni(2+) ions, while moderately inhibited by other ions. In contrast, Mg(2+) ions enhanced the relative activity compared to the control. The acrylamide contents in baked dough were reduced to sixty percent after treatment with recombinant TkAsn as compared to the untreated control. Results of the present study revealed that the enzyme was highly active at broader range of temperatures and pH, which reflect the potential of recombinant TkAsn in the food processing industry. In addition, the high thermal stability of the enzyme may facilitates its handling, storage, and transportation.

First-principles evaluation of transition metal dichalcogenide-graphene pairs functionalized with oxygen-containing groups for sodium-ion battery anodes.

Composites of reduced graphene oxides (rGOs) with transition metal dichalcogenides have garnered considerable attention as promising anode materials for sodium-ion batteries (SIBs) because of their superior theoretical capacity and long-term stability compared with pure graphene. However, the underlying mechanism of how the oxygen functional groups improve the functionality of rGO remains unclear. In this study, we investigated the roles of functional groups in rGO-based heterogeneous bilayers using first-principles density functional theory calculations. The thermodynamic affinities to Na atoms, kinetic diffusion, and working potential behaviors of the Na atoms in various models, such as MoS2/graphene (Gr), MoS2/Gr-O, MoS2/Gr-OH, and MoS2/Gr-COOH, were accurately evaluated. It is clearly demonstrated that the noncovalent bonding nature is a predominant descriptor of Na affinity rather than the charge distribution around the intercalated Na atom. The activation barriers for Na atomic diffusion in the MoS2/Gr, MoS2/Gr-O, MoS2/Gr-OH, and MoS2/Gr-COOH models were estimated to be 0.24, 0.27, 0.35, and 0.31 eV, respectively. This indicated that the functional groups slightly delayed the Na motion. Notably, the obtained results demonstrated that the -COOH group not only enhanced the affinity towards Na intercalation but also induced a low working voltage at approximately 1 V. Therefore, the carboxyl functional group exhibits high material stability, making rGO a promising candidate for SIB anode materials.

The effects of single-dose intravenous dexmedetomidine on hyperbaric bupivacaine spinal anesthesia.

PURPOSE: Dexmedetomidine, a selective α2-adrenoceptor agonist, has analgesic and sedative effects. The purpose of this study was to investigate the effects of small, single-dose intravenous dexmedetomidine administration after hyperbaric bupivacaine spinal anesthesia. METHODS: Sixty adult patients classified as American Society of Anesthesiologists physical status 1 or 2 and scheduled for lower extremity surgery under spinal anesthesia were studied. Patients were randomly assigned to one of three groups and administered hyperbaric intrathecal bupivacaine 12 mg. 5 min after spinal anesthesia, patients in groups 1, 2, and 3 received normal saline 10 ml, dexmedetomidine 0.25 µg/kg, and dexmedetomidine 0.5 µg/kg, respectively, over 10-min intravenous administration. The onset time, maximum block level, two-dermatome sensory regression time, duration of motor and sensory anesthesia, and side effects were assessed. RESULTS: The two-dermatome sensory regression time was significantly increased in groups 2 and 3. The duration of motor and sensory anesthesia was significantly increased in group 3. Onset time, maximum block level, level of sedation, and incidence of hypotension and treatment-needed bradycardia were no different among the groups. CONCLUSION: Single-dose intravenous dexmedetomidine 0.25-0.5 µg/kg, administered 5 min after intrathecal injection of hyperbaric bupivacaine, improved the duration of spinal anesthesia without significant side effects. This method may be useful for increasing the duration of spinal anesthesia, even after intrathecal injection of local anesthetics.

Genomic Analysis of the Carrot Bacterial Blight Pathogen Xanthomonas hortorum pv. carotae in Korea.

Bacterial leaf blight of carrots caused by Xanthomonas hortorum pv. carotae (Xhc) is an important worldwide seed-borne disease. In 2012 and 2013, symptoms similar to bacterial leaf blight were found in carrot farms in Jeju Island, Korea. The phenotypic characteristics of the Korean isolation strains were similar to the type strain of Xhc. Pathogenicity showed symptoms on the 14th day after inoculation on carrot plants. Identification by genetic method was multi-position sequencing of the isolated strain JJ2001 was performed using four genes (danK, gyrB, fyuA, and rpoD). The isolated strain was confirmed to be most similar to Xhc M081. Furthermore, in order to analyze the genetic characteristics of the isolated strain, whole genome analysis was performed through the next-generation sequencing method. The draft genome size of JJ2001 is 5,443,372 bp, which contains 63.57% of G + C and has 4,547 open reading frames. Specifically, the classification of pathovar can be confirmed to be similar to that of the host lineage. Plant pathogenic factors and determinants of the majority of the secretion system are conserved in strain JJ2001. This genetic information enables detailed comparative analysis in the pathovar stage of pathogenic bacteria. Furthermore, these findings provide basic data for the distribution and diagnosis of Xanthomonas hortorum pv. carotae, a major plant pathogen that infects carrots in Korea.

Sex-specific role for the long noncoding RNA Pnky in mouse behavior.

The human brain expresses thousands of different long noncoding RNAs (lncRNAs), and aberrant expression of specific lncRNAs has been associated with cognitive and psychiatric disorders. While a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few have been shown to underlie animal behavior, particularly with genetic strategies that establish lncRNA function in trans. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA underlies specific behavior by functioning in trans. Male Pnky-knockout (KO) mice have deficits in cued fear recall, a type of Pavlovian associative memory. In female Pnky-KO mice, the acoustic startle response (ASR) is increased and accompanied by a decrease in prepulse inhibition (PPI), both of which are behaviors altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome (BAC) transgene reverses the ASR phenotype of female Pnky-KO mice, demonstrating that Pnky underlies specific animal behavior by functioning in trans. More broadly, these data provide genetic evidence that a lncRNA gene and its function in trans can play a key role in the behavior of adult mammals, contributing fundamental knowledge to our growing understanding of the association between specific lncRNAs and disorders of cognition and mood.

Severity identification for internet gaming disorder using heart rate variability reactivity for gaming cues: a deep learning approach.

Background: The diminished executive control along with cue-reactivity has been suggested to play an important role in addiction. Hear rate variability (HRV), which is related to the autonomic nervous system, is a useful biomarker that can reflect cognitive-emotional responses to stimuli. In this study, Internet gaming disorder (IGD) subjects' autonomic response to gaming-related cues was evaluated by measuring HRV changes in exposure to gaming situation. We investigated whether this HRV reactivity can significantly classify the categorical classification according to the severity of IGD. Methods: The present study included 70 subjects and classified them into 4 classes (normal, mild, moderate and severe) according to their IGD severity. We measured HRV for 5 min after the start of their preferred Internet game to reflect the autonomic response upon exposure to gaming. The neural parameters of deep learning model were trained using time-frequency parameters of HRV. Using the Class Activation Mapping (CAM) algorithm, we analyzed whether the deep learning model could predict the severity classification of IGD and which areas of the time-frequency series were mainly involved. Results: The trained deep learning model showed an accuracy of 95.10% and F-1 scores of 0.995 (normal), 0.994 (mild), 0.995 (moderate), and 0.999 (severe) for the four classes of IGD severity classification. As a result of checking the input of the deep learning model using the CAM algorithm, the high frequency (HF)-HRV was related to the severity classification of IGD. In the case of severe IGD, low frequency (LF)-HRV as well as HF-HRV were identified as regions of interest in the deep learning model. Conclusion: In a deep learning model using the time-frequency HRV data, a significant predictor of IGD severity classification was parasympathetic tone reactivity when exposed to gaming situations. The reactivity of the sympathetic tone for the gaming situation could predict only the severe group of IGD. This study suggests that the autonomic response to the game-related cues can reflect the addiction status to the game.

Comparison of pathological outcomes of active surveillance candidates who underwent radical prostatectomy using contemporary protocols at a high-volume Korean center.

OBJECTIVE: We compared contemporary active surveillance protocols based on pathological outcomes in patients who underwent radical prostatectomy. METHODS: We identified the experimental cohort from prostate cancer patients who underwent radical prostatectomy between 2001 and 2011, and who met the inclusion criteria of five published active surveillance protocols, namely Johns Hopkins Medical Institution, University of California at San Francisco, Memorial Sloan-Kettering Cancer Center, University of Miami and Prostate Cancer Research International: Active Surveillance. To compare each protocol, we evaluated the pathological outcomes and calculated the sensitivity, specificity and accuracy for each protocol according to the proportion of organ-confined Gleason≤6 disease. RESULTS: Overall, 376 patients met the inclusion criteria of the active surveillance protocols with 61, 325, 222, 212 and 206 patients meeting the criteria of the Johns Hopkins Medical Institution, University of California at San Francisco, Memorial Sloan-Kettering Cancer Center, University of Miami and Prostate Cancer Research International: Active Surveillance protocols, respectively. The sensitivity and specificity values of the five protocols, respectively, were 0.199 and 0.882 in Johns Hopkins Medical Institution, 0.855 and 0.124 in University of California at San Francisco, 0.638 and 0.468 in Memorial Sloan-Kettering Cancer Center, 0.599 and 0.479 in University of Miami, and 0.609 and 0.527 in Prostate Cancer Research International: Active Surveillance. In terms of both the sensitivity and specificity, Prostate Cancer Research International: Active Surveillance was the most balanced protocol. In addition, Prostate Cancer Research International: Active Surveillance showed a more accurate performance for favourable pathological outcomes than the others. However, using the area under the curve to compare the discriminative ability of each protocol, there were no statistically significant differences. CONCLUSIONS: The contemporary active surveillance protocols showed similar pathological characteristics in patients who had undergone radical prostatectomy. However, we concluded that the Prostate Cancer Research International: Active Surveillance protocol would be most helpful to Korean populations in choosing candidates for active surveillance considering the balance between sensitivity and specificity and the accuracy of diagnosis.

Tuning the Site-to-Site Interaction in Ru-M (M = Co, Fe, Ni) Diatomic Electrocatalysts to Climb up the Volcano Plot of Oxygen Electroreduction.

The modulating of the geometric and electronic structures of metal-N-C atomic catalysts for improving their performance in catalyzing oxygen reduction reactions (ORRs) is highly desirable yet challenging. We herein report a delicate "encapsulation-substitution" strategy for the synthesis of paired metal sites in N-doped carbon. With the regulation of the d-orbital energy level, a significant increment in oxygen electroreduction activity was demonstrated in Ru-Co diatomic catalyst (DAC) compared with other diatomic (Ru-Fe and Ru-Ni) and single-atomic counterparts. The Ru-Co DAC efficiently reduces oxygen with a halfwave potential of 0.895 V vs RHE and a turnover frequency of 2.424 s-1 at 0.7 V, establishing optimal thermodynamic and kinetic behaviors in the triple-phase reaction under practical conditions. Moreover, the Ru-Co DAC electrode displays bifunctional activity in a gas diffusion Zn-air battery with a small voltage gap of 0.603 V, outperforming the commercial Pt/C|RuO2 catalyst. Our findings provide a clear understanding of site-to-site interaction on ORR and a benchmark evaluation of atomic catalysts with correlations of diatomic structure, energy level, and overall catalytic performance at the subnanometer level.