Local Activity Research Articles

Frequency‐Specific Alternations in the Amplitude of Fluctuations in Tension‐Type Headache: A Machine Learning Study

ABSTRACTBrain neural signal at different frequency bands relates to different functions. However, the frequency‐specific properties of spontaneous brain activity in tension‐type headache (TTH)—the most rampant primary headache—remain largely unknown. We investigated the local neural activity of 33 TTH patients and 31 healthy controls (HCs) in the conventional frequency band and two sub‐frequency bands (slow‐4 and slow‐5 frequency band), employing fractional amplitude of low‐frequency fluctuations (fALFF), percent amplitude fluctuations (PerAF) and Wavelet‐ALFF analytic methods. Using age as covariate, we performed two sample t‐test to compare the between‐group differences of each metrics in each frequency band. Support vector machine (SVM) was conducted to classify TTH patients and HCs on the basis of altered spontaneous brain activities. TTH patients showed lower fALFF values in the left cerebellar lobule X, left parahippocampal gyrus, and right supplementary motor area in slow‐5 band. TTH patients showed lower PerAF in the left fusiform and cerebellar regions in three bands. Altered Wavelet‐ALFF values in the right thalamus, left anterior cingulum gyrus, superior parietal gyrus and middle and parietal frontal regions in three frequency bands were detected. And the SVM classifier obtained an overall accuracy of 77.38%, 82.38%, and 95% based on fALFF, PerAF, and Wavelet ALFF values, respectively. TTH patients exhibited abnormal neural activity in various brain regions. The abnormal brain activities serve as powerful features for distinguishing TTH patients. This preliminary exploration provides a novel insight into the underlying mechanism of TTH.

Disorganized thalamic subregional functional connectivity in bipolar I disorder.

Thalamus plays a pivotal role in the pathophysiology of neuropsychiatric conditions due to its strategic position and intricate connectivity with the cerebral cortex, limbic system, and other subcortical structures. In the present study, the potential involvement of the thalamus and subregions of the thalamus are explored in bipolar disorder (BD). In particular, functional and structural magnetic resonance imaging was performed on 73 adult patients with BD-I and 78 healthy controls (HCs). Seed-based thalamus and thalamic subregional functional connectivity (FC) were compared between the BD-I patients and HCs. Compared to HCs, patients with BD-I showed higher FC between the left thalamus and right lingual gyrus and altered FC between the dorsal thalamus and the default mode network and prefrontal regions, which may be correlated with mania symptomatology. In patients with BD-I, the anterior subregions of the thalamus had higher FC than the posterior subregions. No significant difference in gray matter volume or local functional activity was found in the thalamus and thalamic subregions between BD-I and HC. These findings provide evidence of disorganized thalamocortical FC in BD-I, suggesting that the thalamus and its subregions may play important and specific roles in the neural circuitry of BD.

Technological Change and Entrepreneurial Activities: Evidence from China

This study is among the first to examine the impacts of technological change on entrepreneurial activities. Using new registered enterprises data and industrial robot data from 2010 to 2018, we find that robot adoption is broadly negatively associated with regional entrepreneurial activities. However, our analysis reveals a more nuanced understanding, in which robot adoption boosts high-quality entrepreneurial activities in regions, specifically those in technology-based industries, but reduces low-quality entrepreneurial activities. We also find that a favorable labor allocation environment and sufficient labor resources, as well as abundant high-skilled labor resources, can mitigate the negative impact. Credit constraints and the upgrading of industrial structures are effective in mitigating the crowding-out effect. In cities with higher unemployment risks, the negative effect is attenuated. The extent of the negative effect varies depending on the prevailing macroeconomic conditions, and the hukou reform helps to mitigate the negative impact. In addition, robot adoption has a significant spatial spillover effect between adjacent cities. These findings shed light on the effects of industrial robot adoption on local entrepreneurial activities, as well as the role of technological change in fostering entrepreneurial activities. Our findings suggest that it is crucial to grasp the strategic opportunities embedded in technological change to spur entrepreneurship.

Bibliometric study of the state of knowledge of the use of technological platforms in agrotourism businesses

Knowledge management is a vital process in the understanding of agritourism as a local development activity. In this sense, this sector has become an important global partner for the development of labor and technological resources throughout the world; it is part of the socioeconomic reality and is a current determinant for local development. This qualitative research proposes a bibliometric study of the state of the study of the application of technological platforms (TP) to the management of agro-tourism products, using the method of review of documents and research repositories of the Universities of Las Tunas and Holguín in eastern Cuba and the Autonomous University of Querétaro in Mexico. The main results lie in showing the level and depth of current literature regarding the application of technologies in agrotourism management. It concludes with the need to increase studies and recognize the importance of involving technological platforms in the management of agrotourism products.

Tumor-Derived Extracellular Vesicles Enable Tumor Tropism Chemo-Genetherapy for Local Immune Activation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly heterogeneous, lacks accessible therapeutic targets, and features an immunosuppressive tumor microenvironment (TME). Anthracycline-based chemotherapy remains the primary treatment method for TNBC, while the current popular immune checkpoint inhibitors persistently encounter therapeutic resistance. Therefore, there is an urgent need to explore combined therapeutic strategies to remodel the TME and improve the treatment response. Considering the highly specific homing ability of tumor cell-derived vesicles and the key role of the signal transduction and activation of the transcription factor 3 (STAT3) pathway in TNBC, we propose a synergistic therapeutic strategy that integrates gene therapy, chemotherapy, and immunotherapy based on STAT3 short interfering RNA (siSTAT3) and doxorubicin (DOX)-functionalized tumor-derived extracellular vesicles (TEVs) (siSTAT3-DOX@TEV). The in vitro and in vivo results demonstrate that siSTAT3-DOX@TEV target tumor tissues precisely, downregulate STAT3 expression, and synergistically and efficiently induce immunogenic death, thereby reversing the immunosuppressive TME. Moreover, mass cytometry and immunohistochemistry reveal the local immune activation effect of siSTAT3-DOX@TEV, with a significant increase in M1 macrophages, CD4+ T cells, and CD8+ T cells in tumor tissues. These results provide strong hints for the development of TEV-based chemo-gene therapeutic agents for TNBC treatment at the clinical level.

Growth hormone and bone: a basic perspective.

Growth hormone is fundamental for growth during childhood and for maintaining bone mass and homeostasis in the adults. GH deficiency causes decreased bone growth and osteopenia, whereas GH excess causes increased bone fragility and decreased bone quality. In the past, it was common knowledge that GH effects on the skeletal system were due to the production of IGF1 from the liver, which has a huge bone anabolic effect per se. However, with the progress of basic research techniques new light has been shed on the mechanisms underlying GH effect in bone, and it is now clear that GH has effects that go beyond the downstream activation of liver IGFs. Therefore, the purpose of this review is to summarize the milestones in basic research that led to the discovery of GH local activity on bone.

Supraspinal contributions to defective antagonistic inhibition and freezing of gait in Parkinson's disease.

The neuromuscular circuit mechanisms of freezing of gait in Parkinson's disease have received little study. Technological progress enables researchers chronically to sense local field potential activity of the basal ganglia in patients while walking. To study subthalamic activity and the circuit processes of supraspinal contributions to spinal motor integration, we recorded local field potentials, surface EMG of antagonistic leg muscles and gait kinematics in patients while walking and freezing. To evaluate the specificity of our findings, we controlled our findings to internally generated volitional stops. We found specific activation-deactivation abnormalities of oscillatory activity of the subthalamic nucleus both before and during a freeze. Furthermore, we were able to show with synchronization analyses that subthalamo-spinal circuits entrain the spinal motor neurons to a defective timing and activation pattern. The main neuromuscular correlates when turning into freezing were as follows: (i) disturbed reciprocity between antagonistic muscles; (ii) increased co-contraction of the antagonists; (iii) defective activation and time pattern of the gastrocnemius muscle; and (iv) increased subthalamo-muscular coherence with the gastrocnemius muscles before the freeze. Beyond the pathophysiological insights into the supraspinal mechanisms contributing to freezing of gait, our findings have potential to inform the conceptualization of future neurorestorative therapies.

Effects of ketamine on frontoparietal interactions in a rule-based antisaccade task in macaque monkeys.

Cognitive control is engaged by working memory processes and high-demand situations like antisaccade, where one must suppress a prepotent response. While it is known to be supported by the frontoparietal control network, how intra- and inter-areal dynamics contribute to cognitive control processes remain unclear. N-Methyl-D-aspartate glutamate receptors (NMDARs) play a key role in prefrontal dynamics that support cognitive control, and its antagonists, such as ketamine, are known to alter task-related prefrontal activities and impair cognitive performance. However, the role of NMDAR in cognitive control-related frontoparietal dynamics remain underexplored. Here, we simultaneously recorded local field potentials and single unit activities from lateral prefrontal (lPFC) and posterior parietal cortices (PPC) in two male macaque monkeys during a rule-based antisaccade task, with both Rule-Visible (RV) and Rule-Memorized (RM) conditions. In addition to altering the E/I balance in both areas, ketamine had a negative impact on rule-coding in true oscillatory activities. It also reduced frontoparietal coherence in a frequency- and rule-dependent manner. Granger prediction analysis revealed that ketamine induced an overall reduction in bidirectional connectivity. Among antisaccade trials, a greater reduction in lPFC-PPC connectivity during the delay period preceded a greater delay in saccadic onset under the RM condition, and a greater deficit in performance under the RV condition. Lastly, ketamine compromised rule coding in lPFC neurons in both RV and RM conditions, and in PPC neurons only in the RV condition. Our findings demonstrate the utility of acute NMDA receptor antagonist in understanding the mechanisms through which frontoparietal dynamics support cognitive control processes.Significance statement A low dose of ketamine is known to induce a transient cognitive control deficit in healthy humans and animals, but it remains unclear whether this deficit is related to a frontoparietal dysconnection. In macaque monkeys performing a rule-based pro- and anti-saccade task, we found that ketamine impaired information coding in frontoparietal neuron, local oscillations and inter-areal synchrony in a rule- and frequency-dependent manner. Notably, under the antisaccade rule, the amount of impairment in task performance could be predicted by the loss in fronto-parietal connectivity in the period just before the monkeys responded. The observations support the utility of NMDA receptor antagonists like ketamine as a tool to understand the role of frontoparietal dynamics in cognitive control.

Altered intrinsic neural activity and its molecular analyses in first-episode schizophrenia with auditory verbal hallucinations

BackgroundAuditory verbal hallucinations (AVHs) are one of the signature positive symptoms of schizophrenia, affecting a substantial portion of patients with schizophrenia. These hallucinations seriously impact the lives of patients, resulting in a substantial social burden. Recent studies have shown a significant correlation between abnormal local brain activity and the neurobiological mechanisms of AVHs. However, it is not fully clear whether altered intrinsic brain activity in schizophrenia patients with AVHs is correlated with specific neurotransmitter systems.MethodsWe included 50 first-episode, drug-naïve schizophrenia patients with AVHs, 50 patients without AVHs (NAVHs), and 50 age- and sex-matched healthy controls (HCs). The amplitude of low-frequency fluctuation (ALFF) was utilized to explore the altered intrinsic brain activity in the AVH group. Subsequently, we spatially correlated the altered ALFF with neurotransmitter maps using JuSpace.ResultsIn our study, compared to HCs, the AVH group exhibited significantly reduced ALFF in multiple brain regions, mainly including the left precuneus, bilateral supplementary motor areas, bilateral paracentral lobules, bilateral precentral gyri, and bilateral postcentral gyri. The NAVH group showed significantly reduced ALFF in the left inferior occipital gyrus, left calcarine gyrus, and left lingual gyrus compared to HCs. Furthermore, the AVH group showed higher ALFF in the right inferior frontal gyrus compared to the NAVH group. Additionally, these ALFF alterations in the AVH group were closely related to three neurotransmitters, including dopamine, serotonin and norepinephrine.ConclusionWe link neurotransmitters to abnormal intrinsic brain activity in first-episode, drug-naïve schizophrenia patients with AVHs, contributing to a comprehensive understanding of the pathophysiological processes and treatment pathways underlying AVHs.

DFT Computation, Spectroscopic, Hirshfeld Surface, Docking and Topological Analysis on 2,2,5‐Trimethyl‐1,3‐Dioxane‐5‐Carboxylic Acid as Potent Anti‐Cancer Agent

ABSTRACTThe 2,2,5‐trimethyl‐1,3‐dioxane‐5‐carboxylic acid (TDCA) using both theoretical and experimental methods have been studied. The sample has been subjected to XRD, FTIR, FT‐Raman, (C13 and H1) NMR, and UV–vis spectrum analysis. Then, theoretical calculations have been performed at the DFT/B3LYP/6‐311++G(d,p) higher based scale. The theoretical and experimental geometrical parameters and frequencies have been compared well. Theoretical and experimental NMR chemical shifts have been determined. Absorption wavelengths of UV–Vis spectrum were experimentally measured and compared with TD‐DFT predictions. Detailed explanations have been given for frontier molecular orbitals, low density gradient, distribution of Mulliken charges, molecular electrostatic potential (MEP), RDG, localized orbital location, and electron localized activities. Based on the studied 2D image of the Hirschfield surfaces, H···H (65.6%) and O···H/H···O (33.6%) are found as the controlling interactions. A high binding affinity of −6.5 Kcal/mol has been calculated against 4OAR protein. These theoretical findings of the molecule may be used as an anticancer drug candidate, which helps to explain the structural stability, reactivity and anticancer potential of TDCA. High drug affinity for the TDCA has been detected by in silico ADMET prediction.

Circulating levels of neutrophil extracellular traps reflects local neutrophil activity but not fibrinolytic activity in coronary thrombi from patients with ST-elevation myocardial infarction

Abstract Introduction Neutrophil extracellular traps (NETs) are associated with impaired fibrinolysis in ischemic stroke, while NETs degradation enhances lysis of coronary thrombi in ex vivo experiments. Whether circulating NET markers are associated with local fibrinolytic activity in patients with ST-elevation myocardial infarction (STEMI) has not been reported. Purpose We investigated associations between circulating NET markers and gene expression of fibrinolytic markers in aspirated coronary thrombi from patients with STEMI. Furthermore, we explored whether local upregulation of NET formation by peptidylarginine deiminase 4 (PAD4) was reflected in the circulation. Methods Coronary thrombi from 35 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were aspirated and promptly snap-frozen to -80°C. Peripheral blood samples were collected simultaneously. Median time from start of symptoms to PCI was 152 min. Thrombus gene expression of tissue Plasminogen Activator (tPA), urinary-type Plasminogen Activator (uPA), plasminogen-activation inhibitor type 1 (PAI-1) and PAD4 were quantified with RT-PCR. Gene expression of PAD4 was also measured in circulating leukocytes. Circulating NET markers were measured by a fluorescent nucleic acid stain using fluorometry (dsDNA), an in-house ELISA technique (MPO-DNA) and commercial ELISA (H3Cit). Correlations were tested using Spearman’s rho. Results There were no correlations between any of the circulating NET markers and gene expression of the fibrinolytic markers tPA, uPA and PAI-1 in the thrombus. Of the circulating NET markers, dsDNA correlated with thrombus gene expression of PAD4 (rs=0.491 p=0.006), whereas none of the NET markers correlated with gene expression of PAD4 in circulating leukocytes. Conclusion Circulating NET markers were not associated with gene expression of fibrinolytic activity in thrombi from patients with STEMI. Local NET formation in the thrombi, measured as PAD4 expression, was associated with the circulating NET marker dsDNA. These findings suggest that circulating NET markers have limited utility for assessing local fibrinolytic activity, but might reflect PAD4-dependent NET formation in coronary thrombi.

Local ventricular activation at the distal great cardiac vein determines right- and left-sided approach for catheter ablation of outflow tract arrhythmias: a simple and rapid discriminator

Abstract Background When the precordial transition zone (TZ) of idiopathic outflow tract arrhythmias (OTAs) is present around lead V3, it may be difficult to precisely determine which outflow tract is responsible for the origin of the OTAs from the ECG characteristics. Purpose We hypothesized that mapping around the distal portion of the great cardiac vein (dGCV) would be useful for identifying which outflow tract is the origin of OTAs during radiofrequency catheter ablation (RFA). Methods Among 28 OTA patients who underwent dGCV mapping and successful RFA at our institution from June 2021 to February 2024, 16 whose TZ during the OTAs was ＞lead V2 and ＜lead V4 were included in this study. In all patients, activation mapping around the dGCV with the novel 2.7 Fr over-the-wire (OTW)-type decapolar catheter was performed during the OTAs. Results In all patients, the mapping catheter could be easily placed in the dGCV. In patients whose OTAs were successfully ablated from the left-sided OT (n=7), the local ventricular activation time in the dGCV during OTAs preceded the QRS onset (LAT-dGCV) by -26.1±7.0 msec, which was significantly earlier than that of OTAs successfully ablated from the right-sided OT (n=9; -4.0±5.7 msec; p<0.001). An LAT-dGCV >-18 msec indicated a left-sided OTA, and right-sided and left-sided OTAs were completely distinct. Patients with an LAT-dGCV >-18 msec and mapping initiated first in the left-sided OT had shorter procedure times than those with mapping initiated first in the right-sided OT (p<0.001). Conclusions Mapping the dGCV with this OTW-type catheter is easy and safe. The earliness of the local ventricular activation in the dGCV during OTAs could easily and precisely differentiate between right-sided and left-sided OTAs, resulting in a successful ablation with a shorter procedure time.

Accuracy of endocardial abnormal electrogram characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation for ventricular tachycardia ablation

Abstract Background Substrate-based catheter ablation of ventricular tachycardia (VT) has become the mainstay therapy for patients with scar-related VT. Correct identification and timing of abnormal near-field EGMs and discerning it from far-field EGMs, is key for procedural success. The novel CARTO™ Late Activation Mapping (LAM) module provides fast and accurate annotation of near-field EGMs including late abnormal ventricular activation. For the algorithm to succeed, a late boundary (LB) annotation line should be positioned immediately behind the normal near-field EGM, however, since the timing of normal local near-field activation varies greatly throughout the endocardium, there is currently no consensus for the optimal LB positioning. We hypothesized that 17-AHA segmental annotation of the endocardial LB followed by scar-dependent sensitivity settings, will improve the accuracy of the near-field EGM characterization. Purpose To evaluate the accuracy of endocardial abnormal EGM characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation as compared to conventional mid-QRS LB positioning. Methods Five high-resolution substrate voltage maps were obtained from 5 patients (80% male, 68±7 years old, 80% ischemic cardiomyopathy) that underwent a catheter-based ablation for scar-related VT. A personalized CT-derived anatomical reconstruction of the 17-segment AHA model was co-registered offline with the electroanatomic voltage map, using ADAS3D software. Per segment, individual LB timings were set at the highest sensitivity. A gold standard annotation map was created by two independent experts after manual scrutiny of individual EGMs. Next, the expert map was compared to automatic maps created from segmental LB and mid-QRS LB positions at normal, high, highest or mixed (normal/high or normal/highest) sensitivities, focusing on EGM voltage and activation accuracy. Results A mean of 2041±1028 points per map were analyzed. Correct correlation of EGM annotation was found on average in 91% (activation) and 81% (voltage) for all segmental LB positioned maps (segLB), and in 83% (activation) and 77% (voltage) for all mid-QRS LB positioned maps (mid-QRSLB). The highest correlation with expert map for both activation and voltage annotation was found in the mixed sensitivity normal/highest map with segmental LB positioning (activation 98%, voltage 88%). The correlation on activation was significantly superior in the segLB map when compared to the normal sensitivity maps (p=0.0008 for mid-QRSLB and p=0.02 for segLB). For correlation on voltage, the segLBmap with mixed sensitivity was significantly superior compared to three mid-QRSLB maps at normal (p=0.04), high and highest (p=0.01) sensitivity. Conclusion Individualized, 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation provides a possible accurate and clinically-relevant framework for substrate assessment. Prospective validation is needed.

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.

Efficacy and safety of HERG channel agonists for treatment of Long QT Syndrome type 8

Abstract Background Substrate-based approach aimed at repolarization abbreviaton using mexiletine was shown to normalize the QTc interval and reduce the event rate in LQT3, and is now considered standard-of-care. Unfortunately, mexiletine is partially efficacious in other malignant forms of LQTS, such as LQT2 and LQT8. Novel compounds, such as HERG channel agonists, potentially capable of safely and efficaciously abbreviating the repolarization have not been tested in a clinically relevant model. Purpose To investigate the efficacy and safety of repolarization shortening using ICA-105574, the most potent compound belonging to the class of HERG channel agonists, in a clinically relevant, first-in-class porcine model of LQT8. Methods We used a combination of 12-lead ECG and electroanatomical mapping (EAM) to obtain data on the QTc interval, local activation time (LAT), local repolarization time (LRT) and its gradients, and reentrant vulnerability index (RVI), at baseline and after drug administration. We used LQT8 pigs of both genders weighing between 60 kg and 80 kg. All procedures were conducted following local regulations for the care and use of laboratory animals after authorization by relevant authorities. We used mixed effects linear regression model to assess the effect of ICA-105574 on the QTc interval and paired nested t-test to assess the effect of ICA-105574 on EAM-derived parameters. Results As a first step, we assessed the effects of ICA-105574 on the QTc interval. Compared to baseline, a single dose of 3 mg/kg of ICA-105574 resulted in an immediate and pronounced shortening of the QTc interval in all animals (∆QTc at 5 minutes post-injection: -28%, p<0.001). We then investigated repeated intravenous administrations of 3 mg/kg doses at 10-minute intervals for a total of 4 doses (i.e., overall drug dose of 12 mg/kg). Importantly, we did not observe excessive QTc shortening (∆QTc 6 mg/kg: -26%; ∆QTc 9 mg/kg: -26%; ∆QTc 12 mg/kg: -30%, p<0.001 for all) nor did we observe any proarrhythmic events in any of the animals studied. In a second phase of the study, we used EAM to assess the modifications in the arrhythmic substrate induced by ICA-105574. Importantly, ICA-105574 not only shortened the duration of ventricular repolarization (∆LRT: -21%, p=0.017), but also reduced the dispersion of ventricular repolarization (∆Max. LRT gradient: -69%, p=0.020). This, coupled with reduction of the activation delay as compared to baseline (∆LAT: -28%, p=0.072), had a net positive effect on the arrhythmic substrate, as evidenced by an amelioration by 30% of global RVI (∆RVIG,D: -32%, p=0.029). Conclusions In our LQT8 pig model, ICA-105574, a potent HERG channel agonist, safely and efficaciously ameliorated the arrhythmic substrate. These results suggest that HERG channel agonists, as a novel class of antiarrhythmics, could have clinical application as a novel substrate-based therapy for LQT8.Figure 1

Anatomical characteristics of the phrenic nerve and the spontaneous conduction block between the right atrium and the superior vena cava

Abstract Introduction Although the superior vena cava isolation (SVCI) with minimal radiofrequency application using a spontaneous right atrium – superior vena cava (RA-SVC) conduction block has been reported, the anatomical characteristics of the spontaneous RA-SVC conduction block is not clear. Purpose The aim of this study to evaluate the anatomical relationship between the spontaneous RA-SVC conduction block and the phrenic nerve (PN). Methods This study consisted of 73 patients who attempted to undergo SVCI using a RA-SVC conduction block. The RA-SVC conduction block was visualized using the extended early meets late tool with the CARTO3 system. We set the first lower threshold at 1800/total local activation time to optimize the visualization of spontaneous RA-SVC conduction block. If the SVC was not isolated by ablation to the gap of the visualized conduction block line, the lower threshold was increased by 5%, and the new gap was ablated each time. The course of the right PN was detected by pacing with 20 mA /2 ms. The RA-SVC conduction block and the course of the PN were measured with reference to the height of the left atrial roof. The extend of the RA-SVC conduction block and PN were measured in angles with respect to the ventral side (Figure 1). These anatomical parameters were compared between the RA-SVC block line and the PN. Results Sixty-one patients (83.6%) had spontaneous RA-SVC conduction block, and the remaining 12 patients (16.4%) did not. Anatomical characteristics were evaluated in 61 patients with spontaneous RA-SVC conduction block. Compared with the course of the PN, RA-SVC conduction block extended more posteriorly (110 degrees vs 128 degrees, P = 0.013) and more caudally (9.5 mm vs 16.1 mm, P<0.0001) (Figure 2). In the patients who underwent SVCI using a RA-SVC conduction block, any patients did not undergo radiofrequency application on the course of the PN. Conclusion Since the caudal end of the RA-SVC conduction block is posterior to the caudal end of the phrenic nerve, SVCI using the RA-SVC conduction block may be able to avoid ablation near the PN.Figure1Figure2

Spatiotemporal control of transgene expression using an infrared laser in the crustacean Daphnia magna

The crustacean Daphnia magna is an emerging model for ecological and toxicological genomics. However, the lack of methods for spatial and temporal control of gene expression has impaired the elucidation of molecular mechanisms underlying responses to environments in vivo. Here we report local activation of the hsp70 promoter-driven gene cassette in D. magna by the infrared laser-evoked gene operator (IR-LEGO), a method for heating the target cells with infrared irradiation. We identified the heat-inducible promoter upstream of the D. magna hsp70-A gene. Using this promoter, we generated a transgenic Daphnia harboring the heat-shock responsive GFP reporter gene and confirmed that the GFP gene responds to heat treatment not only in juveniles and adults but also in embryos. We collected embryos from the reporter line and irradiated four different regions of interest in the embryos: a proximal region of the third thoracic segment, a part of the midline, a second maxilla, and a distal region of the endopodite of the second antenna, all of which increased GFP fluorescence with an infrared laser. Our results suggest that the IR-LEGO method is useful for spatial and temporal control of gene expression and would advance the functional genomics in D. magna.

Fostering Multicultural Community Harmony to Enhance Peace and Sustainable Development Goals (SDG’s)

Purpose: This service aims to foster harmony in a multicultural community in the city of Solo as a concrete step to increase peace and support the achievement of the Sustainable Development Goals (SDGs). Theoretical Framework: This study uses a cultural integration thinking framework and a participatory approach to building social harmony. The focus is on developing an understanding and appreciation of cultural diversity, as well as increasing positive interactions between ethnicities and religions to create an inclusive environment. Methods: This service uses a participatory approach involving a variety of local stakeholders, including ethnic and religious communities, local governments, and community institutions. Activities include organizing intercultural dialogue workshops, cultural diversity training, and public campaigns to promote tolerance and peace. Results and Conclusion: The results of this service show an increased awareness of cultural diversity and appreciation for differences among the people of Solo. Inter-ethnic and religious interactions are increasing, creating a stronger foundation for social harmony. In conclusion, participatory and integrative approaches are effective in building harmony in multicultural societies to support peace and sustainable development. Implications: This service has a positive impact by increasing tolerance, reducing social conflicts, and strengthening social cohesion in the city of Solo. The impact is also seen in increasing community participation in local development activities and achieving related SDGs targets. Originality/value: Its uniqueness lies in its participatory approach that actively involves all relevant parties, as well as focusing on cultural integration as the main foundation for the development of sustainable social harmony in a multicultural environment such as the city of Solo.

Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness.

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

Corrosion mapping of intermetallic in a dissimilar weldment using in-situ alternating current scanning electrochemical microscopy

In the present work, in-situ corrosion activity mapping across explosively welded 304 L SS-Zr-4 dissimilar joint interfaces was performed using intermittent contact alternating current-scanning electrochemical microscopy (IC-AC-SECM). Two weld joint samples, one with a regular interface and another with an irregular interface, were examined for their local surface activities at an open circuit potential in tap water without using a redox mediator. The SEM micrographs showed the formation of intermetallics at localized regions of the irregular interface weld sample but not in the regular interface sample. The 304 L SS regions of the welds were relatively anodic, with current and impedance magnitude values of 270 ± 20 nA and 380 ± 20 kΩ respectively, when compared to the Zr-4 regions with the corresponding values of 160 ± 20 nA and 630 ± 20 kΩ, due to galvanic coupling effect. The IC-AC-SECM technique enabled the in-situ determination of corrosion activity of localized intermetallic region within the weldment. The current and impedance magnitude values of the intermetallic region were ∼ 240 nA and ∼ 450 kΩ, respectively, showing only a slightly lesser anodic activity as compared to the 304 L SS base metal. The results obtained from the IC-AC-SECM mapping showed a good correlation with the EDS elemental mapping of the dissimilar weldment with intermetallic. The findings indicate the effectiveness of the IC-AC-SECM technique for the in-situ localized corrosion mapping of dissimilar weld joints, showcasing its potential for various applications in assessing weld integrity.