Regulation of RHOV signaling by interaction with SH3 domain-containing adaptor proteins and phosphorylation by PKA.

RHOV and RHOU are considered atypical Rho-family small GTPases because of the existence of N- and C-terminal extension regions, abnormal GDP/GTP cycling, and post-translational modification. Particularly, RHOV and RHOU both have a proline-rich (PR) motif in the N-terminal region. It has been reported that the PR motif of RHOU interacts with GRB2, a SH3 domain-containing adaptor protein, and regulates its activity through EGF receptor signaling. However, it is unknown whether RHOV, like RHOU, interacts with SH3 domain-containing adaptor proteins. In this study, we investigated the interactions between RHOV and SH3 domain-containing adaptor proteins, including GRB2 and NCK2. The RHOV-induced serum response factor (SRF)-dependent gene transcriptional activity was attenuated in cells co-expressing either GRB2 or NCK2 compared to cells expressing RHOV alone. From the results of experiments using various gene mutants of RHOV and GRB2, it appears that the PR motif of the N-terminal region of RHOV is the crucial binding site for the SH3 domain-containing proteins. Furthermore, we found that Ser25 in the N-terminal region of RHOV is phosphorylated by PKA and that its phosphorylation is suppressed by interaction with NCK2 but not GRB2. We have found a novel regulatory mechanism for the phosphorylation of RHOV and its interaction with SH3 domain-containing adaptor proteins.

Substrate-Dependent Alteration in the C- and O-Prenylation Specificities of Cannabis Prenyltransferase.

CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures. Interestingly, the kinetic parameters of CsPT4 for these substrates differed depending on whether they underwent C-prenylation or O-prenylation, suggesting that this enzyme utilized different substrate-binding modes suitable for the respective reactions. Aromatic prenyltransferases that catalyze O-prenylation are rare in the plant kingdom, and CsPT4 was notable for altering the reaction specificity between C- and O-prenylations depending on the skeletons of aromatic substrates. We also demonstrated that enzymatically synthesized geranylated acylphloroglucinols had potent antiausterity activity against PANC-1 human pancreatic cancer cells, with 4'-O-geranyl THDC being the most effective. We suggest that CsPT4 is a valuable catalyst to generate biologically active C- and O-prenylated molecules that could be anticancer lead compounds.

The Rho guanine nucleotide exchange factor PLEKHG1 is activated by interaction with and phosphorylation by Src family kinase member FYN.

Rho family small GTPases (Rho) regulate various cell motility processes by spatiotemporally controlling the actin cytoskeleton. Some Rho-specific guanine nucleotide exchange factors (RhoGEFs) are regulated via tyrosine phosphorylation by Src family tyrosine kinase (SFK). We also previously reported that PLEKHG2, a RhoGEF for the GTPases Rac1 and Cdc42, is tyrosine-phosphorylated by SRC. However, the details of the mechanisms by which SFK regulates RhoGEFs are not well understood. In this study, we found for the first time that PLEKHG1, which has very high homology to the Dbl and pleckstrin homology domains of PLEKHG2, activates Cdc42 following activation by FYN, a member of the SFK family. We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1. We also found that the region containing the Src homology 3 and Src homology 2 domains of FYN is required for this interaction. Finally, we demonstrated that tyrosine phosphorylation of Tyr-720 and Tyr-801 in PLEKHG1 is important for the activation of PLEKHG1. These results suggest that FYN is a regulator of PLEKHG1 and may regulate cell morphology through Rho signaling via the interaction with and tyrosine phosphorylation of PLEKHG1.

Causally informed activity flow models provide mechanistic insight into network-generated cognitive activations.

Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists' preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.

Global connectivity fingerprints predict the domain generality of multiple-demand regions.

A set of distributed cognitive control networks are known to contribute to diverse cognitive demands, yet it is unclear how these networks gain this domain-general capacity. We hypothesized that this capacity is largely due to the particular organization of the human brain's intrinsic network architecture. Specifically, we tested the possibility that each brain region's domain generality is reflected in its level of global (hub-like) intrinsic connectivity as well as its particular global connectivity pattern ("connectivity fingerprint"). Consistent with prior work, we found that cognitive control networks exhibited domain generality as they represented diverse task context information covering sensory, motor response, and logic rule domains. Supporting our hypothesis, we found that the level of global intrinsic connectivity (estimated with resting-state functional magnetic resonance imaging [fMRI]) was correlated with domain generality during tasks. Further, using a novel information fingerprint mapping approach, we found that each cognitive control region's unique rule response profile("information fingerprint") could be predicted based on its unique intrinsic connectivity fingerprint and the information content in regions outside cognitive control networks. Together, these results suggest that the human brain's intrinsic network architecture supports its ability to represent diverse cognitive task information largely via the location of multiple-demand regions within the brain's global network organization.

Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats.

Danazol (DNZ) is a synthetic androgen derivative used for the treatment of intractable hematological disorders. In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 h after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system.The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein expression of CYP3A.In contrast to the intravenous administration, serum MDZ concentrations in DNZ-treated rats were markedly higher than those in control rats when administered orally. DNZ treatment increased MDZ oral bioavailability by approximately 2.5-folds.We herein demonstrated that DNZ increased the bioavailability of orally administered MDZ through irreversible inactivation of hepatic and intestinal CYP3A in rats.

[A Case of Penile Calciphylaxis in a Hemodialysis Patient].

In the present case of a 56-year-old male, hemodialysis was introduced from December 20XX-2 due to chronic renal failure caused by diabetic nephropathy. In February 20XX, a glans penis ulcer was observed. It gradually expanded. Angiography conducted in April revealed complete occlusion of the left internal pudendal artery and poor visualization of the bilateral penile arteries. Given the high risk of obstruction, endovascular treatment was not conducted. The glans penis ulcer continued to expand, and maintenance dialysis became difficult due to intractable pain. Opioids were introduced, but the pain could not be controlled. In May 20XX, the patient was referred to our department for surgical treatment, and partial penile resection was performed. The patient was diagnosed with penile calciphylaxis based on clinical findings and pathological diagnosis. After the surgery, the pain subsided considerably, and the patient is being followed on an out-patient basis.

The Functional Relevance of Task-State Functional Connectivity.

Resting-state functional connectivity has provided substantial insight into intrinsic brain network organization, yet the functional importance of task-related change from that intrinsic network organization remains unclear. Indeed, such task-related changes are known to be small, suggesting they may have only minimal functional relevance. Alternatively, despite their small amplitude, these task-related changes may be essential for the ability of the human brain to adaptively alter its functionality via rapid changes in inter-regional relationships. We used activity flow mapping-an approach for building empirically derived network models-to quantify the functional importance of task-state functional connectivity (above and beyond resting-state functional connectivity) in shaping cognitive task activations in the (female and male) human brain. We found that task-state functional connectivity could be used to better predict independent fMRI activations across all 24 task conditions and all 360 cortical regions tested. Further, we found that prediction accuracy was strongly driven by individual-specific functional connectivity patterns, while functional connectivity patterns from other tasks (task-general functional connectivity) still improved predictions beyond resting-state functional connectivity. Additionally, since activity flow models simulate how task-evoked activations (which underlie behavior) are generated, these results may provide mechanistic insight into why prior studies found correlations between task-state functional connectivity and individual differences in behavior. These findings suggest that task-related changes to functional connections play an important role in dynamically reshaping brain network organization, shifting the flow of neural activity during task performance.SIGNIFICANCE STATEMENT Human cognition is highly dynamic, yet the functional network organization of the human brain is highly similar across rest and task states. We hypothesized that, despite this overall network stability, task-related changes from the intrinsic (resting-state) network organization of the brain strongly contribute to brain activations during cognitive task performance. Given that cognitive task activations emerge through network interactions, we leveraged connectivity-based models to predict independent cognitive task activations using resting-state versus task-state functional connectivity. This revealed that task-related changes in functional network organization increased prediction accuracy of cognitive task activations substantially, demonstrating their likely functional relevance for dynamic cognitive processes despite the small size of these task-related network changes.

A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction.

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach-connectome-wide similarity-we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.

Flexible Coordinator and Switcher Hubs for Adaptive Task Control.

Functional connectivity (FC) studies have identified at least two large-scale neural systems that constitute cognitive control networks, the frontoparietal network (FPN) and cingulo-opercular network (CON). Control networks are thought to support goal-directed cognition and behavior. It was previously shown that the FPN flexibly shifts its global connectivity pattern according to task goal, consistent with a "flexible hub" mechanism for cognitive control. Our aim was to build on this finding to develop a functional cartography (a multimetric profile) of control networks in terms of dynamic network properties. We quantified network properties in (male and female) humans using a high-control-demand cognitive paradigm involving switching among 64 task sets. We hypothesized that cognitive control is enacted by the FPN and CON via distinct but complementary roles reflected in network dynamics. Consistent with a flexible "coordinator" mechanism, FPN connections were varied across tasks, while maintaining within-network connectivity to aid cross-region coordination. Consistent with a flexible "switcher" mechanism, CON regions switched to other networks in a task-dependent manner, driven primarily by reduced within-network connections to other CON regions. This pattern of results suggests FPN acts as a dynamic, global coordinator of goal-relevant information, while CON transiently disbands to lend processing resources to other goal-relevant networks. This cartography of network dynamics reveals a dissociation between two prominent cognitive control networks, suggesting complementary mechanisms underlying goal-directed cognition.SIGNIFICANCE STATEMENT Cognitive control supports a variety of behaviors requiring flexible cognition, such as rapidly switching between tasks. Furthermore, cognitive control is negatively impacted in a variety of mental illnesses. We used tools from network science to characterize the implementation of cognitive control by large-scale brain systems. This revealed that two systems, the frontoparietal (FPN) and cingulo-opercular (CON) networks, have distinct but complementary roles in controlling global network reconfigurations. The FPN exhibited properties of a flexible coordinator (orchestrating task changes), while CON acted as a flexible switcher (switching specific regions to other systems to lend processing resources). These findings reveal an underlying distinction in cognitive processes that may be applicable to clinical, educational, and machine learning work targeting cognitive flexibility.

Task-evoked activity quenches neural correlations and variability across cortical areas.

Many large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhancing their information coding by suppressing shared spontaneous activity. Here we sought to adjudicate between these conflicting perspectives, assessing whether co-active brain regions during task states tend to increase or decrease their correlations. We found that variability and correlations primarily decrease across a variety of cortical regions in two highly distinct data sets: non-human primate spiking data and human functional magnetic resonance imaging data. Moreover, this observed variability and correlation reduction was accompanied by an overall increase in dimensionality (reflecting less information redundancy) during task states, suggesting that decreased correlations increased information coding capacity. We further found in both spiking and neural mass computational models that task-evoked activity increased the stability around a stable attractor, globally quenching neural variability and correlations. Together, our results provide an integrative mechanistic account that encompasses measures of large-scale neural activity, variability, and correlations during resting and task states.

Differences in clinical outcomes between pre- and post-marketing clinical study following paclitaxel-coated balloon catheter treatment for coronary in-stent restenosis: from the Japanese regulatory viewpoint.

In 2013, a drug-coated balloon catheter (DCB) (SeQuent Please) for the treatment of coronary in-stent restenosis (ISR) was approved in Japan. The pre-marketing Japan domestic NP001 study demonstrated better outcomes of the DCB (n = 138) compared to plain balloon angioplasty (n = 72). After the introduction to marketing, a post-marketing surveillance (PMS) (n = 396) was conducted to evaluate the safety and efficacy of the DCB in Japanese routine clinical practice. The aim of this paper was to assess differences between the pre-marketing NP001 study and the PMS. Compared to the NP001 study, more complex lesions were treated in the PMS (type B2/C: 69.0% vs 20.4%, total occlusion: 11.2% vs 0%, p < 0.001, respectively) and target lesion was more frequently ISR related to drug-eluting stent (DES) (79.5% vs 39.4%, p < 0.001). Regarding clinical outcomes, the rate of target lesion revascularization (TLR) was higher in the PMS than in the NP001 study (TLR: 12.9% at 7 months and 17.6% at 12 months vs 2.8% at 6 months, p = 0.001, p < 0.001, respectively). Multivariable logistic regression analysis revealed that DES-ISR was a risk factor of TLR after DCB treatment for ISR (odds ratio: 5.77, 95% CI 1.75-18.95, p = 0.004). Among representative published trials using DCB for ISR, clinical outcomes are often worse in DES-ISR trials than those in bare metal stent-ISR trials. The rates of TLR in previous DES-ISR trials are similar to that in the current PMS (TLR at 12 months: 22.1% for ISAR-DESIRE 3, 15.3% for PEPCAD-DES, and 13.0% for RIBS IV). The effectiveness and safety of DCB for coronary ISR have been confirmed in the Japanese real-world survey. PMS would be useful to evaluate the safety and effectiveness of medical products throughout their total life cycles.

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells.

Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells. Our results showed that all proteins were expressed at mRNA and protein levels and that all ERM proteins were highly colocalized with PD-L1 in the plasma membrane. Interestingly, immunoprecipitation assay results demonstrated that PD-L1 interacted with ERM as well as actin cytoskeleton proteins. Furthermore, gene silencing of ezrin, but not radixin and moesin, remarkably decreased the protein expression of PD-L1 without affecting its mRNA expression. In conclusion, ezrin may function as a scaffold protein for PD-L1; regulate PD-L1 protein expression, possibly via post-translational modification in HeLa cells; and serve as a potential therapeutic target for cervical cancer, improving the current immune checkpoint blockade therapy.

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A.

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.

[A Case of Pelvic Lymph Node Recurrence Detected by PSMA PET/CT after Primary Proton Beam Radiotherapy for Prostate Cancer].

The patient is a 72-year-old man who was referred to our hospital with an elevated prostate specific antigen (PSA) level. He was diagnosed with prostate cancer (cT2aN0M0) at the age of 62 years. He had undergone radical proton beam radiotherapy. The PSA level decreased to a nadir of 0.217 ng/ml after 5 years, gradually increasing thereafter to 1.595 ng/ml during the next 5 years. Although magnetic resonance imaging of the prostate showed an abnormal signal area in the prostate, repeated biopsies of the prostate revealed no malignant findings. Contrast-enhanced abdominal computed tomography (CT), bone scintigraphy and fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/CT did not detect any abnormalities in the prostate or metastatic lesions. ¹8F-prostate specific membrane antigen (PSMA)-PET/CT showed no accumulation in the prostate, but some accumulation in a left obturator lymph node. Open pelvic lymph node dissection was performed, and pathological examination confirmed lymph node metastasis from the prostate cancer. The PSA level decreased from 2.482 ng/ml preoperatively to 0.391 ng/ml at 3 months postoperatively. PSMA-PET/CT might be useful for early localization of recurrent lesions in biochemical recurrence after radical treatment for prostate cancer.

[Double Infectious Aortic Aneurysms Followed by Positron Emission Tomography/Computed Tomography for Evaluation of Infection Control after Simultaneous Thoracic Endovascular Aortic Repair and Endovascular Aortic Repair:Report of a Case].

An 81-year-old male was referred to our institute. His chief complaint was high fever. Computed tomography (CT) angiography demonstrated newly saccular aortic aneurysms at both thoracic and abdominal aorta. We used intravenous antibiotics( ceftriaxone 4 g/day) for seven days. Positron emission tomography (PET)/CT showed active inflammation sign at both chest and abdominal aneurysms. Open surgery for double aortic aneurysms seemed too invasive because of his past medical history. At eighth day after admission, we performed thoracic endovascular aortic repair( TEVAR) and endovascular aortic repair (EVAR) for preventing rupture of aortic aneurysms. After surgery, we continued intravenous antibiotics (ceftriaxone 4 g/day) for 15 days. We changed intravenous antibiotics to oral antibiotics( levofloxacin 500 mg/day). The postoperative course was uneventful. He was discharged at 19th day after surgery. Since surgery, no symptoms of reinfection have been observed at outpatient clinic. PET/CT was useful to evaluate the control of local infection in this case.

A cortical hierarchy of localized and distributed processes revealed via dissociation of task activations, connectivity changes, and intrinsic timescales.

Many studies have identified the role of localized and distributed cognitive functionality by mapping either local task-related activity or distributed functional connectivity (FC). However, few studies have directly explored the relationship between a brain region's localized task activity and its distributed task FC. Here we systematically evaluated the differential contributions of task-related activity and FC changes to identify a relationship between localized and distributed processes across the cortical hierarchy. We found that across multiple tasks, the magnitude of regional task-evoked activity was high in unimodal areas, but low in transmodal areas. In contrast, we found that task-state FC was significantly reduced in unimodal areas relative to transmodal areas. This revealed a strong negative relationship between localized task activity and distributed FC across cortical regions that was associated with the previously reported principal gradient of macroscale organization. Moreover, this dissociation corresponded to hierarchical cortical differences in the intrinsic timescale estimated from resting-state fMRI and region myelin content estimated from structural MRI. Together, our results contribute to a growing literature illustrating the differential contributions of a hierarchical cortical gradient representing localized and distributed cognitive processes.

Transcranial alternating current stimulation attenuates BOLD adaptation and increases functional connectivity.

Transcranial alternating current stimulation (tACS) is used as a noninvasive tool for cognitive enhancement and clinical applications. The physiological effects of tACS, however, are complex and poorly understood. Most studies of tACS focus on its ability to entrain brain oscillations, but our behavioral results in humans and extracellular recordings in nonhuman primates support the view that tACS at 10 Hz also affects brain function by reducing sensory adaptation. Our primary goal in the present study is to test this hypothesis using blood oxygen level-dependent (BOLD) imaging in human subjects. Using concurrent functional magnetic resonance imaging (fMRI) and tACS, and a motion adaptation paradigm developed to quantify BOLD adaptation, we show that tACS significantly attenuates adaptation in the human motion area (hMT+). In addition, an exploratory analysis shows that tACS increases functional connectivity of the stimulated hMT+ with the rest of the brain and the dorsal attention network in particular. Based on field estimates from individualized head models, we relate these changes to the strength of tACS-induced electric fields. Specifically, we report that functional connectivity (between hMT+ and any other region of interest) increases in proportion to the field strength in the region of interest. These findings add support for the claim that weak 10-Hz currents applied to the scalp modulate both local and global measures of brain activity.NEW & NOTEWORTHY Concurrent transcranial alternating current stimulation (tACS) and functional MRI show that tACS affects the human brain by attenuating adaptation and increasing functional connectivity in a dose-dependent manner. This work is important for our basic understanding of what tACS does, but also for therapeutic applications, which need insight into the full range of ways in which tACS affects the brain.

Independent Factors for In-Hospital Death Following Drug-Eluting Stent Thrombosis From the Japanese Adverse Event Report System.

BACKGROUND: Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST. CONCLUSIONS: LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

Task activations produce spurious but systematic inflation of task functional connectivity estimates.

Most neuroscientific studies have focused on task-evoked activations (activity amplitudes at specific brain locations), providing limited insight into the functional relationships between separate brain locations. Task-state functional connectivity (FC) - statistical association between brain activity time series during task performance - moves beyond task-evoked activations by quantifying functional interactions during tasks. However, many task-state FC studies do not remove the first-order effect of task-evoked activations prior to estimating task-state FC. It has been argued that this results in the ambiguous inference "likely active or interacting during the task", rather than the intended inference "likely interacting during the task". Utilizing a neural mass computational model, we verified that task-evoked activations substantially and inappropriately inflate task-state FC estimates, especially in functional MRI (fMRI) data. Various methods attempting to address this problem have been developed, yet the efficacies of these approaches have not been systematically assessed. We found that most standard approaches for fitting and removing mean task-evoked activations were unable to correct these inflated correlations. In contrast, methods that flexibly fit mean task-evoked response shapes effectively corrected the inflated correlations without reducing effects of interest. Results with empirical fMRI data confirmed the model's predictions, revealing activation-induced task-state FC inflation for both Pearson correlation and psychophysiological interaction (PPI) approaches. These results demonstrate that removal of mean task-evoked activations using an approach that flexibly models task-evoked response shape is an important preprocessing step for valid estimation of task-state FC.