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Background and purposePrevious studies predicting the rupture risk of intracranial aneurysms (IAs) have predominantly utilized static imaging data, overlooking the dynamic blood flow and biomechanical properties of the aneurysm wall. Irregular pulsation detected by 4D-CTA is a potential predictor of aneurysm rupture, albeit with uncertain clinical significance. This study aimed to analyze the changes in morpho-hemodynamic characteristics of IAs during the cardiac cycle to elucidate the dynamic changes and the associated hemodynamic mechanisms.MethodsA retrospective review was conducted on the 4D-CTA data of IA patients between January 2017 and September 2019. R-R intervals were segmented into 20-time phases, reconstructing 20 CT datasets to identify irregular pulsation and extract 3D aneurysm models. Computational fluid dynamics (CFD) simulations analyzed hemodynamic parameters such as oscillatory shear index (OSI) and relative residence time (RRT). Changes in morpho-hemodynamic characteristics were quantified in terms of the absolute change (parameter*) and relative change rate (parameter%). Rupture risk was assessed using the rupture resemblance model (RRS).ResultsEleven UIAs from 10 patients were finally included, with five aneurysms showing irregular pulsation (45.45%). No significant differences in morpho-hemodynamic characteristics were observed between aneurysms with or without irregular pulsation. More remarkable changes in aneurysm size (size*: 0.59 ± 0.14 mm vs. 0.32 ± 0.12 mm, p = 0.010; size%: 10.49% ± 1.43% vs. 3.95% ± 1.79%, p

Abstract Background Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist. Methods This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke. Results The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk. Conclusions Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted pathogenesis disease and the exact mechanisms driving HFpEF have not been completely elucidated. Pressure overload hypertrophy (POH) related fibroblasts and M2 macrophages in HFpEF myocardium have been recently identified and are now of great interest. Sympathetic overdrive has also been implicated in HFpEF. This study is designed to dynamically observe the potential roles of aforementioned mechanisms in pathological remodeling and cardiac dysfunction in chronic PO rats. Surgical constriction of the abdominal aorta was used for induction of HFpEF. Echocardiography, electrocardiogram, hemodynamic measurement, hematoxylin and eosin staining, Masson staining, immunohistochemistry and immunofluorescence were performed to assess the changes in heart dysfunction, cardiac remodeling and driving mechanisms at different time points (2, 18, 24 weeks). The PO induced HFpEF model was well established, which was confirmed by the persistent increase in carotid artery systolic and diastolic blood pressure, and left ventricle hypertrophy at the corresponding postoperative stage. Meanwhile, PO hypertrophy gradually developed into HFpEF, associated with QT and QTc intervals prolongation, normal systolic (EF was maintained at >50%) but impaired diastolic function (increasing LVEDP and LV -dP/dtmin, abnormal E/A ratio), increased myocytes size, and observed relatively slight inflammatory infiltration but robust reactive fibrosis. IHC staining further confirmed that macrophages (CD68) but not neutrophils (MPO) or T cells (CD3) accounted for a predominant proportion of infiltrating cells. Mechanistically, we found that the infiltrating macrophages in the heart expressed high levels of CD206 which was simultaneously adjacent to POH fibroblasts appeared to overexpression of α-SMA in PO rats at late stages. Interestingly, we distinguished two different POHF sub-populations during PO induced HFpEF development, according to non overlapping signals of α-SMA and PDGFRα/β proteins. Additionally, PO led to a pronounced exaggeration in sympathetic fibers at all time points. These findings suggest that the establishing model here begins with cardiac sympathetic overdrive, subsequently along with immune cells especially M2 macrophage accumulation and fibroblast heterogeneity at later stages is associated with the development of cardiac maladaptive remodeling and diastolic dysfunction thus further progression to HFpEF.

Abstract HPV16 and 18 are positively correlated with cervical carcinogenesis. However, HPV prevalence tends to vary according to region, nationality, and environment. The most prevalent high-risk (HR) HPV genotypes are HPV16, 52, 58, 56, 18, 33, and 45), while the low-risk (LR) genotypes are HPV6 and 11 in the Chinese population. Importantly, undetectable low-copy HPV DNA could be an important indicator of integration into the human genome and may be a precursor to cancer progression. The HPV viral load changes dramatically, either increasing or decreasing rapidly during carcinogenesis, and traditional quantitative real-time PCR (qPCR) cannot accurately capture this subtle change. Therefore, in this study, a reliable droplet digital PCR (ddPCR) method was developed to simultaneously detect and quantify HPV genotypes. The ddPCR quantitative results showed high accuracy, sensitivity, and specificity compared to qPCR results employing the same clinical specimens and supplemented the ddPCR assay for HPV52/56/58/6 genotypes according to the infection specificity of the Chinese population. In summary, this procedure is valuable for quantifying HPV DNA, especially under conditions of low template copy number in cervical intraepithelial neoplasia (CIN) and/or cervical cancer. Additionally, this method can dynamically observe the prognosis and outcome of HPV infection and thus be used as an effective means for real-time monitoring of tumor load.

Background and purposeIrregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics.Materials and methodsFourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter’s absolute change and relative rates of change during the cardiac cycle.ResultsSeven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms (< 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased (p = 0.035), but the relative rates of change in aneurysm size (p = 0.013), height (p = 0.014), width (p = 0.008), height-to-width ratio (p = 0.009), dome-to-neck ratio (p = 0.019) and bottleneck factor (p = 0.012) decreased.ConclusionAlthough the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-of-concept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs.

Abstract Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks. Participants were 37.8 years (SD = 12.4), 68% women, 25% Black, 24% Latino, and 11% Asian. Activation of the right dlPFC (neural region of interest in cognitive control) decreased in the intervention group but increased in the control group, with an effect size meeting the prespecified threshold for a meaningful effect (Cohen’s d = 0.3). Between-group differences in the change in activation of the left dlPFC and bilateral amygdala were observed, but were of smaller magnitude (d = 0.2). Change in right dlPFC activation was also meaningfully associated (r ≥ 0.4) with changes in self-reported problem-solving ability and avoidance in the intervention. Lumen intervention also led to decreased HADS depression, anxiety, and overall psychological distress scores, with medium effect sizes (Cohen’s d = 0.49, 0.51, and 0.55, respectively), compared with the waitlist control group. This pilot trial showed promising effects of a novel digital mental health intervention on cognitive control using neuroimaging and depression and anxiety symptoms, providing foundational evidence for a future confirmatory study.

BackgroundThe quality of user interaction with therapeutic tools has been positively associated with treatment response; however, no studies have investigated these relationships for voice-based digital tools. ObjectiveThis study evaluated the relationships between objective and subjective user interaction measures as well as treatment response on Lumen, a novel voice-based coach, delivering problem-solving treatment to patients with mild to moderate depression or anxiety or both. MethodsIn a pilot trial, 42 adults with clinically significant depression (Patient Health Questionnaire-9 [PHQ-9]) or anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) symptoms or both received Lumen, a voice-based coach delivering 8 problem-solving treatment sessions. Objective (number of conversational breakdowns, ie, instances where a participant’s voice input could not be interpreted by Lumen) and subjective user interaction measures (task-related workload, user experience, and treatment alliance) were obtained for each session. Changes in PHQ-9 and GAD-7 scores at each ensuing session after session 1 measured the treatment response. ResultsParticipants were 38.9 (SD 12.9) years old, 28 (67%) were women, 8 (19%) were Black, 12 (29%) were Latino, 5 (12%) were Asian, and 28 (67%) had a high school or college education. Mean (SD) across sessions showed breakdowns (mean 6.5, SD 4.4 to mean 2.3, SD 1.8) decreasing over sessions, favorable task-related workload (mean 14.5, SD 5.6 to mean 17.6, SD 5.6) decreasing over sessions, neutral-to-positive user experience (mean 0.5, SD 1.4 to mean 1.1, SD 1.3), and high treatment alliance (mean 5.0, SD 1.4 to mean 5.3, SD 0.9). PHQ-9 (Ptrend=.001) and GAD-7 scores (Ptrend=.01) improved significantly over sessions. Treatment alliance correlated with improvements in PHQ-9 (Pearson r=–0.02 to –0.46) and GAD-7 (r=0.03 to –0.57) scores across sessions, whereas breakdowns and task-related workload did not. Mixed models showed that participants with higher individual mean treatment alliance had greater improvements in PHQ-9 (β=–1.13, 95% CI –2.16 to –0.10) and GAD-7 (β=–1.17, 95% CI –2.13 to –0.20) scores. ConclusionsThe participants had fewer conversational breakdowns and largely favorable user interactions with Lumen across sessions. Conversational breakdowns were not associated with subjective user interaction measures or treatment responses, highlighting how participants adapted and effectively used Lumen. Individuals experiencing higher treatment alliance had greater improvements in depression and anxiety. Understanding treatment alliance can provide insights on improving treatment response for this new delivery modality, which provides accessibility, flexibility, comfort with disclosure, and cost-related advantages compared to conventional psychotherapy. Trial RegistrationClinicalTrials.gov NCT04524104; https://clinicaltrials.gov/study/NCT04524104

In recent years, multi-bucket foundations have been studied and gradually adopted in engineering practices as a novel foundation for offshore wind turbines within a range of water depth of 30 to 50 m. This study investigated the motion characteristics of air-floating tripod bucket foundation (AFTBF) through a series of experiments during free air-floating. The experimental results show that the surge force appears to be the most important factor influencing pitch moment and motion, whether it is a change in water depth or a draft for AFTBF. The maximum amplitudes of surge acceleration and pitch angle show a trend of increasing with narrower spacing and decreasing with wider spacing, while the heave acceleration shows an opposite trend. The added mass and damping of heave motion for AFTBF increase with shallower water due to the increasing pressure difference between the inside and bottom of bucket foundation. The shallower the water depth and the larger the draft, the longer the resonance period of heave.

Abstract Background This study intended to clarify the mechanisms by which WISP1-mediated IGF1/αvβ3/Wnt axis might affect the progression of ovarian cancer. Methods Bioinformatics analysis was implemented for pinpointing expression of IGF1 and WISP1 which was verified through expression determination in clinical tissue samples and cells. Next, gain- or loss-of-function experimentations were implemented for testing CAOV4 and SKOV3 cell biological processes. The interaction between WISP1 and IGF1 was verified by co-immunoprecipitation and the molecular mechanism was analyzed. Finally, ovarian cancer nude mouse models were prepared to unveil the in vivo effects of WISP1/IGF1. Results IGF1 and WISP1 expression was elevated in ovarian cancer tissues and cells, which shared correlation with poor prognosis of ovarian cancer sufferers. Elevated IGF1 induced malignant properties of ovarian cancer cells through activation of PI3K-Akt and Wnt signaling pathway. WISP1 was positively correlated with IGF1. WISP1 could enhance the interaction between IGF1 and αvβ3 to induce epithelial-mesenchymal transition. In vivo experiments also confirmed that upregulated WISP1/IGF1 induced tumorigenesis and metastasis of ovarian cancer cells. Conclusion In conclusion, WISP1 can facilitate ovarian cancer by activating Wnt via the interaction between IGF1 and αvβ3.

In order to further improve the combination of strength and ductility for 30Si2MnCrMoVE ultra-high strength steel (UHSS), a thermomechanical treatment, named deformation direct quenching and partitioning (DQ&P), was carried out on it. The microstructure evolutions and mechanical properties of 30Si2MnCrMoVE UHSS treated by DQ&P were compared with those treated by conventional off-line quenching and tempering (Q&T) through various microscopic characterization methods and uniaxial tensile tests. Moreover, the effects of austempering temperature on the microstructure evolutions and mechanical properties of the studied steel after DQ&P process were also investigated. The results show that the DQ&P samples, although lower or slightly lower yield strength, possess significantly higher ultimate tensile strength due to higher work-hardening rate caused by high density dislocations and fine dispersed carbides. Moreover, DQ&P310 sample exhibit apparently higher uniform elongation than Q&T sample despite of comparable content of retained austenite due to more prone to transformation induced plasticity (TRIP) effect. The DQ&P process can increase the ultimate tensile strength by 267 MPã423 MPa and the uniform elongation by 78%∼85%, respectively, as compared to Q&T process, which indicates that DQ&P process may be a promising thermomechanical treatment method to improve the comprehensive mechanical properties of the studied steel. The strengths and elongations of DQ&P samples do not vary monotonously with the increase of austempering temperature, which are both closely related to the content of retained austenite.

It is a central issue to eliminate radioactive uranium (U(VI)) efficiently from water. In this manuscript, β-cyclodextrin was cross-linked with 2,3,5,6-tetrafluoro-1,4-benzenedicarbonitrile, and then a carboxylation reaction was used to prepare porous cross-linked polymers rich in carboxyl groups (CA-PCDPs). Subsequently, magnetic nanoparticles (MNPs) were loaded onto the CA-PCDPs via coprecipitation, and magnetic porous β-cyclodextrin polymer nanoparticles (CA-PCDP@MNPs) were successfully obtained, which were used for efficient elimination of U(VI) from nuclear wastewater solution. Moreover, SEM, FTIR, VSM, BET, and XRD were employed to investigate the CA-PCDP@MNP and found that it had a well-developed porous structure, high specific surface area, and abundant oxygen-containing functional groups (carboxyl, hydroxyl, C-O-C, Fe-O, etc.), providing sufficient active sites for chelating uranyl ions. Experiments illustrated that the CA-PCDP@MNP had efficient removal ability for U(VI), and the maximum theoretical adsorption amount for U(VI) reached 245.66 mg/g at pH 6.0 and 303 K. Moreover, the adsorption process was more suitable for the quasi second-order kinetic model and Langmuir adsorption isotherm model, indicating that the adsorption process was chemical adsorption. Meanwhile, the CA-PCDP@MNPs also exhibited fast response magnetic recovery ability and excellent regeneration and recycling ability. In addition, the data of the adsorption mechanism demonstrated that oxygen-containing functional groups, which were rich on the surface of CA-PCDP@MNPs, were the main binding active sites of U(VI). From the above results, it can be deduced that the CA-PCDP@MNP has a good application prospect in the practical application of nuclear wastewater treatment.

The latest 2021 WHO classification redefines glioblastoma (GBM) as the hierarchical reporting standard by eliminating glioblastoma, IDH-mutant and only retaining the tumor entity of “glioblastoma, IDH-wild type.” Knowing that subclassification of tumors based on molecular features is supposed to facilitate the therapeutic choice and increase the response rate in cancer patients, it is necessary to carry out molecular classification of the newly defined GBM. Although differentiation trajectory inference based on single-cell sequencing (scRNA-seq) data holds great promise for identifying cell heterogeneity, it has not been used in the study of GBM molecular classification. Single-cell transcriptome sequencing data from 10 GBM samples were used to identify molecular classification based on differentiation trajectories. The expressions of identified features were validated by public bulk RNA-sequencing data. Clinical feasibility of the classification system was examined in tissue samples by immunohistochemical (IHC) staining and immunofluorescence, and their clinical significance was investigated in public cohorts and clinical samples with complete clinical follow-up information. By analyzing scRNA-seq data of 10 GBM samples, four differentiation trajectories from the glioblastoma stem cell-like (GSCL) cluster were identified, based on which malignant cells were classified into five characteristic subclusters. Each cluster exhibited different potential drug sensitivities, pathways, functions, and transcriptional modules. The classification model was further examined in TCGA and CGGA datasets. According to the different abundance of five characteristic cell clusters, the patients were classified into five groups which we named Ac-G, Class-G, Neo-G, Opc-G, and Undiff-G groups. It was found that the Undiff-G group exhibited the worst overall survival (OS) in both TCGA and CGGA cohorts. In addition, the classification model was verified by IHC staining in 137 GBM samples to further clarify the difference in OS between the five groups. Furthermore, the novel biomarkers of glioblastoma stem cells (GSCs) were also described. In summary, we identified five classifications of GBM and found that they exhibited distinct drug sensitivities and different prognoses, suggesting that the new grouping system may be able to provide important prognostic information and have certain guiding significance for the treatment of GBM, and identified the GSCL cluster in GBM tissues and described its characteristic program, which may help develop new potential therapeutic targets for GSCs in GBM.

BackgroundApplication of stent-assisted coiling and FD in acute phase of ruptured wide-necked aneurysms is relatively contraindicated due to the potential risk of ischemic and hemorrhagic complications. Scheduled stenting after initial coiling has emerged as an alternative paradigm for ruptured wide-necked aneurysms. The objective of this study is to evaluate the safety and efficacy of a strategy of staged stent-assisted coiling in acutely ruptured saccular wide-necked intracranial aneurysms compared with conventional early stent-assisted coiling strategy via propensity score matching in a high-volume center.MethodsA retrospective review of patients with acutely ruptured saccular wide-necked intracranial aneurysms who underwent staged stent-assisted coiling or conventional stent-assisted coiling from November 2014 to November 2019 was performed. Perioperative procedure-related complications and clinical and angiographic follow-up outcomes were compared.ResultsA total of 69 patients with staged stent-assisted coiling and 138 patients with conventional stent-assisted coiling were enrolled after 1:2 propensity score matching. The median interval time between previous coiling and later stenting was 4.0 weeks (range 3.5–7.5 weeks). No rebleeding occurred during the intervals. The rate of immediate complete occlusion was lower with initial coiling before scheduled stenting than with conventional stent-assisted coiling (21.7 vs. 60.9%), whereas comparable results were observed at follow-up (82.5 vs. 72.9%; p = 0.357). The clinical follow-up outcomes, overall procedure-related complications and procedure-related mortality between the two groups demonstrated no significant differences (P = 0.232, P = 0.089, P = 0.537, respectively). Multivariate analysis showed that modified Fisher grades (OR = 2.120, P = 0.041) were independent predictors for overall procedure-related complications and no significant predictors for hemorrhagic and ischemic complications.ConclusionsStaged stent-assisted coiling is a safe and effective treatment strategy for acutely ruptured saccular wide-necked intracranial aneurysms, with comparable complete occlusion rates, recurrence rates at follow-up and overall procedure-related complication rates compared with conventional stent-assisted coiling strategy. Staged stent-assisted coiling could be an alternative treatment option for selected ruptured intracranial aneurysms in the future.

The development of automated segmentation and quantitative characterization of microtextured regions (MTRs) from the complex heterogeneous microstructures is urgently needed, since MTRs have been proven to be the critical issue that dominates the dwell-fatigue performance of aerospace components. In addition, MTRs in Ti alloys have similarities to microstructures encountered in other materials, including minerals and biomaterials. Meanwhile, machine learning (ML) offers new opportunities. This paper addresses segmentation and quantitative characterization of MTRs, where an ML approach, the Gaussian mixture models (GMMs) coupled with density-based spatial clustering of applications with noise (DBSCAN) clustering algorithms, was employed in order to process the orientation data acquired via EBSD in the Matlab environment. Pixels with orientation information acquired through electron backscatter diffraction (EBSD) are divided and colored into several “classes” (MTRs) within the defined c-axis misorientations (i.e., 25°, 20°, 15°, 10°, and 5°), the precision and efficacy of which are verified by the morphology and pole figure of the segmented MTR. An appropriate range of c-axis misorientations for MTR segmentation was derived, i.e., 15~20°. The contribution of this innovative technique is compared with previous studies. At the same time, the MTRs were statistically characterized in the global region.

ObjectiveThis study aims to compare the safety and efficacy of stent-assisted coiling (SAC) with those of coiling alone (CA) for the treatment of ruptured tiny intracranial aneurysms.MethodsWe enrolled 245 patients with ruptured tiny intracranial aneurysms treated with coil embolization. Patients were grouped into SAC and CA groups. Baseline characteristics, periprocedural complications, clinical outcomes, and angiographic results were compared between the two groups. In addition, a subgroup analysis was conducted in the SAC group, and patients were regrouped into low-profile visualized intraluminal support (LVIS) and laser-cut groups to compare the perioperative procedure-related complications and clinical and angiographic follow-up outcomes.ResultsAll baseline characteristics were equivalent between the two groups except for aneurysm size and dome-to-neck aspect ratio. The rates of overall procedure-related complications, intraprocedural rupture, postoperative early rebleeding, intraprocedural thrombosis, postprocedural thrombosis, and procedure-related mortality were comparable between the two groups (P = 0.105, 0.145, 0.308, 1.000, 1.000, 0.160, respectively). Nevertheless, the rate of hemorrhagic complication in the SAC group was significantly higher (P = 0.023). The angiographic follow-up outcomes showed that the SAC group had a higher complete occlusion rate and lower recurrence rate (88.2 vs. 67.1%, 5.4 vs. 15.2%, P = 0.001). The clinical outcomes at discharge and follow-up between the two groups demonstrated no significant differences (P = 0.192 and P = 0.085, respectively). For subgroup analysis, LVIS stents were associated with a significantly higher rate of complete occlusion (P = 0.014) and a lower rate of intraprocedural rupture (p = 0.021). Moreover, multivariate analysis showed that there were no predictors for the overall, hemorrhagic, and ischemic procedure-related complications, while Raymond class was an independent predictor of retreatment (OR = 3.508, 95% CI 1.168–11.603; P = 0.029).ConclusionStent-assisted coiling may increase the incidence of hemorrhagic events with favorable angiographic results and comparable clinical outcomes compared with stand-alone coiling. Nevertheless, LVIS stent could improve the safety compared with lazer-cut stent. Simultaneously, considering the better long-term effect, LVIS stent-assisted coiling may be a preferable choice for ruptured tiny intracranial aneurysms.

ObjectiveDelayed aneurysm rupture is a fatal complication after flow diversion treatment for large and giant intracranial aneurysms. This study aimed to investigate the feasibility and safety of coiling first and followed by planned flow diversion to prevent delayed aneurysm rupture.MethodsFrom January 2017 to December 2021 in two institutions, patients with unruptured intracranial aneurysms treated by coiling first and planned flow diversion were retrospectively collected. Data on demographic and aneurysmal characteristics, procedural details, and clinical and angiographic outcomes were reviewed.ResultsThirty patients were included (7 Males and 23 Females; Median age 57 years). Aneurysmal size ranged from 11.8 to 26.8 mm, with a median value of 18.5 mm. All aneurysms were located within the intradural segment of internal carotid arteries. Coiling and planned flow diversion were successfully performed in all patients. The time interval between coiling and flow diversion was 3.9–6.7 weeks, with a median value of 5.2 weeks. No hemorrhagic or ischemic complications occurred during the procedures and follow-up. Complete or subtotal occlusion was achieved in 86.7% (26/30) at the last angiographic follow-up (median 6.7 months).ConclusionThe preliminary data suggested that coiling unruptured intracranial aneurysms followed by planned flow diversion is both safe and effective. Further studies with larger cohorts are needed to verify the effect of this new strategy in preventing delayed rupture after flow diversion.

BackgroundArtificial intelligence has provided new opportunities for human interactions with technology for the practice of medicine. Among the recent artificial intelligence innovations, personal voice assistants have been broadly adopted. This highlights their potential for health care–related applications such as behavioral counseling to promote healthy lifestyle habits and emotional well-being. However, the use of voice-based applications for behavioral therapy has not been previously evaluated. ObjectiveThis study aimed to conduct a formative user evaluation of Lumen, a virtual voice-based coach developed as an Alexa skill that delivers evidence-based, problem-solving treatment for patients with mild to moderate depression and/or anxiety. MethodsA total of 26 participants completed 2 therapy sessions—an introductory (session 1) and a problem-solving (session 2)—with Lumen. Following each session with Lumen, participants completed user experience, task-related workload, and work alliance surveys. They also participated in semistructured interviews addressing the benefits, challenges and barriers to Lumen use, and design recommendations. We evaluated the differences in user experience, task load, and work alliance between sessions using 2-tailed paired t tests. Interview transcripts were coded using an inductive thematic analysis to characterize the participants’ perspectives regarding Lumen use. ResultsParticipants found Lumen to provide high pragmatic usability and favorable user experience, with marginal task load during interactions for both Lumen sessions. However, participants experienced a higher temporal workload during the problem-solving session, suggesting a feeling of being rushed during their communicative interactions. On the basis of the qualitative analysis, the following themes were identified: Lumen’s on-demand accessibility and the delivery of a complex problem-solving treatment task with a simplistic structure for achieving therapy goals; themes related to Lumen improvements included streamlining and improved personalization of conversations, slower pacing of conversations, and providing additional context during therapy sessions. ConclusionsOn the basis of an in-depth formative evaluation, we found that Lumen supported the ability to conduct cognitively plausible interactions for the delivery of behavioral therapy. Several design suggestions identified from the study including reducing temporal and cognitive load during conversational interactions, developing more natural conversations, and expanding privacy and security features were incorporated in the revised version of Lumen. Although further research is needed, the promising findings from this study highlight the potential for using Lumen to deliver personalized and accessible mental health care, filling a gap in traditional mental health services.

Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4–8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains (p = 0.537, p = 0.551, p = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children’s neurodevelopmental and respiratory function may be warranted.

BackgroundAlthough Latino men have the highest prevalence (45%) of obesity among all men in the United States, traditional weight loss interventions have not effectively engaged this hard-to-reach and diverse group. Offering choices among technology-mediated weight loss interventions may offer advantages. ObjectiveThe aim of this study is to examine Latino men’s preferences among 3 weight loss intervention options. We also examined whether attendance in group sessions (videoconference and in person) and weight loss differed according to intervention choice. MethodsLatino men (n=200; mean age 47.3, SD 11.8 years) participated in a comparative effectiveness trial based on primary care and were randomized to receive the 1-year HOMBRE (Hombres con Opciones para Mejorar su Bienestar para Reducir Enfermedades Crónicas; English translation: Men With Options to Improve Their Well-being and Reduce Chronic Disease) intervention. HOMBRE is a weight loss intervention that offers 3 delivery options. During an orientation session, a trained bilingual coach helped men select 1 of the 3 intervention options that differed in coach, peer support, and available language. We used canonical discriminant analysis to assess multivariate associations of demographic, clinical, employment, cultural, and technology use and access factors with men’s intervention choices. We used generalized linear models to estimate weight loss at 6, 12, and 18 months for men in each intervention option. ResultsAmong Latino men, 28% (56/200) chose videoconference groups, 31% (62/200) chose web-based videos, and 41% (82/200) chose in-person groups. The canonical discriminant analysis identified 1 orthogonal dimension that distinguished between men who chose an in-person group and men who chose web-based videos. Men who were older, spoke Spanish, and did not use a computer frequently had a higher probability of choosing in-person groups versus web-based videos. For men who selected a group delivery option, 86.9% (107/123) attended ≥25% of the sessions, 83.7% (103/123) attended ≥50% of the sessions, and 73.2% (90/123) attended ≥75% of the sessions, with no differences by type of group (videoconference or in person). Men who chose videoconference and in-person group sessions lost significantly more weight at 6 months (both P

ObjectiveThe treatment of unruptured small intracranial aneurysms remains controversial. A distinguishing characteristic of A1 segment aneurysms is that they tend to rupture when they are small, which may be related to their distinctive morphology and hemodynamics. Our study sought to investigate the rupture risk factors of A1 segment aneurysms by analyzing the clinical risk factors, morphology, and hemodynamic characteristics of A1 segment aneurysms.MethodsWe retrospectively enrolled 49 (23 ruptured, 26 unruptured) consecutive patients presenting to our institute with A1 segment aneurysms between January 2010 and March 2020. Independent risk factors associated with the rupture of A1 segment aneurysms were analyzed by multivariate regression analysis in the ruptured group and unruptured group.ResultsClinical risk factors, including age, sex, hypertension, smoking history, and SAH family history revealed no difference between the ruptured and unruptured groups. The ruptured group presented a significantly larger size (Size, P = 0.007), aspect ratio (AR, P = 0.002), size ratio (SR, P = 0.001), bottleneck index (BN, P = 0.016), dome-to-neck ratio (DN, P = 0.001), and oscillatory shear index (OSI) (P = 0.001) than the unruptured group. The normalized wall shear stress (NWSS) of the ruptured aneurysms was lower than the unruptured group (P = 0.001). In the multivariate regression analysis, only SR (OR = 3.672, P = 0.003) and NWSS (OR = 0.474, P = 0.01) were independent risk factors in the A1 segment aneurysm rupture.ConclusionA higher SR and lower NWSS revealed a close connection with the rupture of A1 segment aneurysms in our study, thus providing a reference for clinical decision-making in treating A1 segment unruptured aneurysms.

Neuronal ceroid lipofuscinoses (NCLs) are among the most common progressive encephalopathies of childhood. Neuronal ceroid lipofuscinosis 7 (CLN7), one of the late infantile-onset NCLs, is an autosomal recessive disorder caused by mutations in the MFSD8 gene on chromosome 4q28. Almost all reported mutations of MFSD8 in CLN7 patients were SNVs. However, we report a 4-year-old boy with CLN7 harboring compound heterozygous mutations in the MFSD8 gene, including one novel two-nucleotide deletion c.136_137delAT (p. M46Vfs*22) and one whole gene deletion of MFSD8 confirmed by Sanger sequencing, genomic quantitative PCR and CNV-seq. Therefore, for nonconsanguineous CLN7 patients with homozygous mutations in the MFSD8 gene, genetic counseling staff should focus on the possibility of whole gene deletion. This is one case report describing a whole gene deletion in a Chinese patient with CLN7, suggesting the diagnosis of CLN7 should be based on clinical suspicion and genetic testing.

Abstract Background Today, approximately one in five United States adolescents age 12 to 19 years is obese and just over a third are either overweight or obese. This study examines how parents and peers influence diet and physical activity behaviors of older adolescents (14–18 years) with overweight or obesity to inform weight management interventions. Methods Adolescent participants included 14 to 18-year-olds with a Body Mass Index (BMI) greater than the 85th percentile for their age and sex who were receiving care in a large healthcare system in Northern California. Adolescents and their parents participated in separate focus groups and interviews (if not able to attend focus groups) that were held at the same time in the same location. We used qualitative thematic analysis to identify common themes discussed in the adolescent and parent focus groups as well as paired analysis of adolescent-parent dyads. Results Participants included 26 adolescents and 27 parents. Adolescent participants were 14 to 18 years old. Half were female and the participants were almost evenly distributed across year in school. The majority self-identified as White (56%) and Asian (36%).Three themes were identified which included 1) parents overestimated how supportive they were compared to adolescents’ perception 2) parents and adolescents had different views regarding parental influence on adolescent diet and physical activity behaviors 3) parents and adolescents held similar views on peers’ influential role on lifestyle behaviors. Conclusion Parents’ and adolescents’ differing views suggest that alignment of parent and adolescent expectations and behaviors for supporting effective weight management could be incorporated into interventions.

Background Infantile pneumonia (IP) seriously affects the health of children. This article mainly discussed the protective effect of long non-coding RNA NKILA (lnc NKILA) on IP by detecting cell viability, apoptosis and inflammatory response of MRC5 cells.Methods Cell counting kit-8 (CCK-8) was used to detect cell viability, while flow cytometry was used to detect cell apoptosis. The expression of apoptosis-associated factors (Bcl-2, Bax, PARP and Cleaved-PARP) and NF-κB and JNK pathway-related factors (t-IκBα, p-IκBα, t-p65, p-p65, β-actin, t-JNK and p-JNK) were tested by western blot. Otherwise, productions of inflammatory factors interleukin (IL)-1β and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA) and western blot. Furthermore, RNA levels were respectively tested and changed by RT-qPCR and cell transfection.Results Tumour necrosis factor-α (TNF-α) treatment reduced cell viability, induced cell apoptosis and promoted inflammatory factors expression. NKILA overexpression remitted TNF-α-induced injury. Moreover, NKILA positively regulated miR-21. miR-21 inhibition could weaken the functions of NKILA overexpression on TNF-α-induced injury. At last, NKILA and miR-21 were involved in the regulation of JNK and NF-κB pathways.Conclusions NKILA overexpression remitted TNF-α-induced MRC5 cell injury by up-regulation of miR-21 and via inactivation of JNK and NF-κB signaling pathways.

Abstract Background Indigenous people in the United States are at high risk for diabetes. Psychosocial stressors like historical trauma may impede success in diabetes prevention programs. Methods A comparative effectiveness trial compared a culturally tailored diabetes prevention program (standard group) with an enhanced one that addressed psychosocial stressors (enhanced group) in 2015 to 2017. Participants were 207 Indigenous adults with a body mass index (BMI) of ≥30 and one additional criterion of metabolic syndrome, and were randomized to the standard or enhanced group. Both groups received a culturally tailored behavioral diabetes prevention program. Strategies to address psychosocial stressors were provided to the enhanced group only. Change in BMI over 12 months was the primary outcome. Secondary outcomes included change in quality of life, and clinical, behavioral, and psychosocial measures at 6 and 12 months. Results The two groups did not significantly differ in BMI change at 12 months. The two groups also did not differ in any secondary outcomes at 6 or 12 months, with the exception of unhealthy food consumption; the standard group reported a larger mean decrease (95% CI) in consumption of unhealthy food compared with the enhanced group (− 4.6 [− 6.8, − 2.5] vs. -0.7 [− 2.9, 1.4], p = 0.01). At 6 months, significant improvements in weight and the physical component of the quality of life measure were observed for both groups compared with their baseline level. Compared with baseline, at 12 months, the standard group showed significant improvement in BMI (mean [95% CI], − 0.5 [− 1.0, − 0.1]) and the enhanced group showed significant improvement in the physical component of the quality of life (2.9 [0.7, 5.2]). Conclusions Adding strategies to address psychosocial barriers to a culturally tailored diabetes prevention program was not successful for improving weight loss among urban Indigenous adults. Trial Registration (if applicable): NCT02266576. Registered October 17, 2014 on clinicaltrials.gov. The trial was prospectively registered.

Abstract Background Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylation-mediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described. Methods Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions. Results The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH. Conclusion Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods: This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings: PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation: The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368

Long noncoding RNAs (lncRNAs) have increasingly been shown to be important biological regulators involved in numerous diseases. Further, increasing evidence demonstrates that circulating lncRNAs can be used as diagnostic biomarkers. Therefore, the purpose of this study was to evaluate the potential for circulating lncRNAs as novel biomarkers for the diagnosis of preeclampsia. In the present study, we measured the expression of five lncRNAs known to be relevant to the uterus in whole blood samples from 48 preeclampsia patients and 24 non-preeclampsia healthy subjects using qRT-PCR. We found that circulating levels of lncRNA BC030099 were significantly higher in patients with preeclampsia (1.232 ± 0.4870) than in non-preeclampsia healthy subjects (0.9928 ± 0.2008, p < 0.05). The area under the receiver operating characteristic (ROC) curve for lncRNA BC030099 was 0.713. Univariate and multivariate analyses identified lncRNA BC030099 as an independent predictor for preeclampsia. In brief, our results suggest that increased plasma levels of lncRNA BC030099 are associated with an increased risk of preeclampsia and may be considered a novel biomarker. Keywords: lncRNA, biomarker, preeclampsia, peripheral blood

Abstract Background Cardiac hypertrophy and acute myocardial infarction (AMI) are two common heart diseases worldwide. However, research is needed into the exact pathogenesis and effective treatment strategies for these diseases. Recently, microRNAs (miRNAs) have been suggested to regulate the pathological pathways of heart disease, indicating a potential role in novel treatments. Results In our study, we constructed a miRNA-gene-drug network and analyzed its topological features. We also identified some significantly dysregulated miRNA-gene-drug triplets (MGDTs) in cardiac hypertrophy and AMI using a computational method. Then, we characterized the activity score profile features for MGDTs in cardiac hypertrophy and AMI. The functional analyses suggested that the genes in the network held special functions. We extracted an insulin-like growth factor 1 receptor-related subnetwork in cardiac hypertrophy and a vascular endothelial growth factor A-related subnetwork in AMI. Finally, we considered insulin-like growth factor 1 receptor and vascular endothelial growth factor A as two candidate drug targets by utilizing the cardiac hypertrophy and AMI pathways. Conclusion These results provide novel insights into the mechanisms and treatment of cardiac hypertrophy and AMI.

BackgroundAn integrated collaborative care intervention was used to treat primary care patients with comorbid obesity and depression in a randomized clinical trial. To increase wider uptake and dissemination, information is needed on translational potential.MethodsThe trial collected longitudinal, qualitative data at baseline, 6 months (end of intensive treatment), 12 months (end of maintenance treatment), and 24 months (end of follow-up). Semi-structured interviews (n = 142) were conducted with 54 out of 409 randomly selected trial participants and 37 other stakeholders, such as recruitment staff, intervention staff, and clinicians. Using a Framework Analysis approach, we examined themes across time and stakeholder groups according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework.ResultsAt baseline, participants and other stakeholders reported being skeptical of the collaborative care approach related to some RE-AIM dimensions. However, over time they indicated greater confidence regarding the potential for future public health impact. They also provided information on barriers and actionable information to enhance program reach, effectiveness, adoption, implementation, and maintenance.ConclusionsRE-AIM provided a useful framework for understanding how to increase the impact of a collaborative and integrative approach for treating comorbid obesity and depression. It also demonstrates the utility of using the framework as a planning tool early in the evidence-generation pipeline.

This study performed a series of comparable experiments (with or without column chromatography) to evaluate whether non-deviated Cu isotope ratios can be obtained directly by Nu Plasma II multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) using standard-sample bracketing with Ga as internal mass bias correction model (C-SSBIN) without column chromatography. Twelve Cu-dominated minerals (copper plate, native copper, chalcopyrite, bornite, chalcocite, digenite, covellite, tetrahedrite, azurite, malachite, atacamite, and cyanotrichite) displayed little drift in δ65Cu values compared with those of minerals with column chromatography, with Δδ65Cuwithout−with ranging from −0.04 to +0.02‰. This means that Cu isotope ratios in Cu-dominated minerals can be achieved without column chromatography, due to the simple matrix and the stability of the machine by using C-SSBIN mode. The acidity and internal standard concentration mismatch effects, as well as the matrix effect, were strictly assessed by Nu Plasma II MC-ICP-MS in a wet-plasma mode in the State Key Laboratory of Continental Dynamics (SKLCD). Finally, a long-term reproducibility of better than ±0.03‰ [n = 38, 2 standard deviations (2s)] were achieved by repeatedly measuring chalcopyrite without column chromatography over 4 months.

Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide range of biological processes and diseases. However, lnc-FFL network motifs have not been systematically investigated in GDM, and their role in the disease remains largely unknown. In the present study, a global lnc-FFL network was constructed and analyzed. Glycometabolism- and hormone-related lnc-FFL networks were extracted from the global network. An integrated algorithm was designed to identify dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. The patterns of dysregulated lnc-FFLs in GDM were complex. Moreover, there were strong associations between dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. Core modules were extracted from the dysregulated lnc-FFL networks in GDM and showed specific and essential functions. In addition, dysregulated lnc-FFLs could combine with ceRNAs and form more complex modules, which could play novel roles in GDM. Notably, we discovered that the dysregulated lnc-FFLs were enriched in the thyroid hormone signaling pathway. Some drug-repurposing candidates, such as hormonal drugs, could be identified based on lnc-FFLs in GDM. In summary, the present study highlighted the effect of dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM and revealed their potential for the discovery of novel biomarkers and therapeutic targets for GDM.

[This corrects the article DOI: 10.1371/journal.pone.0231743.].

IntroductionThe RAINBOW randomized clinical trial validated the efficacy of an integrated collaborative care intervention for obesity and depression in primary care, although the effect was modest. To inform intervention optimization, this study investigated within-treatment variability in participant engagement and progress.MethodsData were collected in 2014-2017 and analyzed post hoc in 2018. Cluster analysis evaluated patterns of change in weekly self-monitored weight from week 6 up to week 52 and depression scores on the Patient Health Questionnaire-9 (PHQ-9) from up to 15 individual sessions during the 12-month intervention. Chi-square tests and ANOVA compared weight loss and depression outcomes objectively measured by blinded assessors to validate differences among categories of treatment engagement and progress defined based on cluster analysis results.ResultsAmong 204 intervention participants (50.9 [SD, 12.2] years, 71% female, 72% non-Hispanic White, BMI 36.7 [6.9], PHQ-9 14.1 [3.2]), 31% (n = 63) had poor engagement, on average completing self-monitored weight in ConclusionsParticipants demonstrating poor engagement or poor progress could be identified early during the intervention and were more likely to fail treatment at the end of the intervention. This insight could inform individualized and timely optimization to enhance treatment efficacy.Trial registrationClinicalTrials.gov# NCT02246413.

Natural killer (NK) cells are innate immune effectors with potent antitumor activity. However, tumor cells can create an immunosuppressive microenvironment to escape immune surveillance. Although accumulating evidence indicates that microenvironmental hypoxia plays an important role in favoring tumor development and immune evasion, it remains unclear by what means hypoxia directly impairs NK cell antitumor activity. In this study, we confirmed that hypoxic NK cells showed significantly lower cytotoxicity against tumor cells. Consistent with this finding, we found that the reduction in NK cell cytotoxicity resulting from hypoxia correlated to the lower expression of granzyme B, IFN-γ, and degranulation marker CD107a, as well as activating receptors including NKp30, NKp46, and NKG2D expressed on the surface of NK cells. More importantly, we further demonstrated that a reduction in the phosphorylation levels of ERK and STAT3 secondary to hypoxia was strongly associated with the attenuated NK cell cytotoxicity. Focusing on the mechanism responsible for reduced phosphorylation levels of ERK and STAT3, we reveal that the activation of protein tyrosine phosphatase SHP-1 (Src homology region 2 domain-containing phosphatase-1) following hypoxia might play an essential role in this process. By knocking down SHP-1 or blocking its activity using a specific inhibitor TPI-1, we were able to partially restore NK cell cytotoxicity under hypoxia. Taken together, we demonstrate that hypoxia could impair NK cell cytotoxicity by decreasing the phosphorylation levels of ERK and STAT3 in a SHP-1-dependent manner. Therefore, targeting SHP-1 could provide an approach to enhance NK cell-based tumor immunotherapy.

The objective of this study is to characterize profiles of obese depressed participants using baseline data collected from October 2014 through December 2016 for an ongoing randomized controlled trial (n=409) in Bay Area, California, USA. Four comorbidity severity categories were defined by interaction of the binary levels of body mass index (BMI) and depression Symptom Checklist 20 (SCL20) scores. Sociodemographic, behavioral, clinical and psychosocial characteristics were measured. Mean (SD) age was 51 (12.1) years, BMI 36.7 (6.4) kg/m2, and SCL20 1.5 (0.5). Participants in the 4 comorbidity severity categories had similar sociodemographic characteristics, but differed significantly in the other characteristics. Two statistically significant canonical dimensions were identified. Participants with BMI≥35 and SCL20≥1.5 differed significantly from those with BMI

In order to develop new-typed multifunctional composite nanofibers, PANI/Fe3O4/PVP flexible bifunctional composite nanofibers with simultaneous electrical conduction and magnetism have been successfully fabricated via a facile electrospinning technology. Polyvinyl pyrrolidone (PVP) is used as a matrix to construct composite nanofibers containing different amounts of polyaniline (PANI) and Fe3O4 nanoparticles (NPs). The bifunctional composite nanofibers simultaneously possess excellent electrical conductivity and magnetic properties. The electrical conductivity reaches up to the order of 10-3 S · cm-1. The electrical conductivity and saturation magnetization of the composite nanofibers can be respectively tuned by adding various amounts of PANI and Fe3O4 NPs. The obtained electricity-magnetism bifunctional composite nanofibers are expected to possess many potential applications in areas such as electromagnetic interference shielding, special coating, microwave absorption, molecular electronics and future nanomechanics. More importantly, the design concept and construct technique are of universal significance to fabricate other bifunctional one-dimensional nanostructures.

Few studies have used nationally representative data to focus specifically on gender differences in weight-related outcomes. This article examines gender differences in weight-related outcomes across the body mass index (BMI) spectrum in overweight and obese adults. Data from the National Health and Nutrition Examination Survey 2009–2010 was analyzed. Weight-related outcomes were accurate weight perception, weight dissatisfaction, attempted weight loss, successful weight loss, and weight loss strategies. Compared with women, overweight and obese men were less likely to have accurate weight perception (odds ratio [OR] = 0.36; 95% confidence interval [CI] = 0.30–0.44), weight dissatisfaction (OR = 0.39; 95% CI = 0.32–0.47), and attempted weight loss (OR = 0.55; 95% CI = 0.48–0.63). The modifying effect of gender on these associations decreased as BMI increased. By BMI 35, the mean probability of women and men to have accurate weight perception and weight dissatisfaction was 90%; attempted weight loss was 60% (women) and 50% (men). At lower BMIs, men had up to 40% less probability than women for these weight loss outcomes. Men who attempted weight loss were more likely than women to lose and maintain ≥10 lb over 1 year (OR = 1.41; 95% CI = 1.20–1.65) and increase exercise and eat less fat as weight loss strategies; women were more likely to join weight loss programs, take prescription diet pills, and follow special diets. A need exists for male-specific interventions to improve overweight and obese men’s likelihood for accurate weight perception, attempted weight loss, and ultimately, successful weight loss.

BACKGROUND AND PURPOSE:The conflicting findings of previous morphological and hemodynamic studies on intracranial aneurysm rupture may be caused by the relatively small sample sizes and the variation in location of the patient-specific aneurysm models. We aimed to determine the discriminators for aneurysm rupture status by focusing on only posterior communicating artery (PCoA) aneurysms. MATERIALS AND METHODS:In 129 PCoA aneurysms (85 ruptured, 44 unruptured), clinical, morphological and hemodynamic characteristics were compared between the ruptured and unruptured cases. Multivariate logistic regression analysis was performed to determine the discriminators for rupture status of PCoA aneurysms. RESULTS:While univariate analyses showed that the size of aneurysm dome, aspect ratio (AR), size ratio (SR), dome-to-neck ratio (DN), inflow angle (IA), normalized wall shear stress (NWSS) and percentage of low wall shear stress area (LSA) were significantly associated with PCoA aneurysm rupture status. With multivariate analyses, significance was only retained for higher IA (OR = 1.539, p < 0.001) and LSA (OR = 1.393, p = 0.041). CONCLUSIONS:Hemodynamics and morphology were related to rupture status of intracranial aneurysms. Higher IA and LSA were identified as discriminators for rupture status of PCoA aneurysms.

Dendrobium officinale Kimu et Migo has increased many researchers' interest for its high medical and horticultural values and the molecular mechanism of its protocorm development remains unclear. In this study, 19 genes from 26 most stably expressed genes in whole transcriptome of protocorms and 5 housekeeping genes were used as candidate reference genes and screened with 4 application softwares (geNorm, NormFinder, BestKeeper and RefFinder). The results showed that a few reference genes could effectively normalize expression level of specific genes in protocorm development and the optimal top 2 reference genes were ASS and APH1L. Meanwhile, validation of GNOM, AP2 and temperature induced gene (TIL) for normalization demonstrates the usefulness of the validated candidate reference genes. The expression profiles of these genes varied under protocorms and temperature stress according to the stablest and unstablest reference genes, which proved the importance of the choice of appropriate reference genes. The first systematic evaluation of stably expressed genes will be very useful in the future analysis of specific genes expression in D. officinale.

PurposeFlow diverters (FD) are increasingly being considered for treating large or giant wide-neck aneurysms. Clinical outcome is highly variable and depends on the type of aneurysm, the flow diverting device and treatment strategies. The objective of this study was to analyze the effect of different flow diverting strategies together with parent artery curvature variations on altering intra-aneurysmal hemodynamics.MethodsFour ideal intracranial aneurysm models with different parent artery curvature were constructed. Computational fluid dynamics (CFD) simulations of the hemodynamics before and after applying five types of flow diverting strategies (single FD, single FD with 5% and 10% packing density of coils, two FDs with 25% and 50% overlapping rate) were performed. Changes in pressure, wall shear stress (WSS), relative residence time (RRT), inflow velocity and inflow volume rate were calculated and compared.ResultsEach flow diverting strategy resulted in enhancement of RRT and reduction of normalized mean WSS, inflow volume rate and inflow velocity in various levels. Among them, 50% overlapped FD induced most effective hemodynamic changes in RRT and inflow volume rate. The mean pressure only slightly decreased after treatment. Regardless of the kind of implantation of FD, the mean pressure, inflow volume rate and inflow velocity increased and the RRT decreased as the curvature of the parent artery increased.ConclusionsOf all flow diverting strategies, overlapping FDs induced most favorable hemodynamic changes. Hemodynamics alterations post treatment were substantially influenced by parent artery curvature. Our results indicate the need of an individualized flow diverting strategy that is tailored for a specific aneurysm.

Author affiliations *Corresponding authors Sulfur isotopes serve as critical tracers for understanding the material sources and cycling in earth science. The in situ sulfur isotope ratio analysis by laser ablation multiple-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) has been a proven important technique, yet the precision and accuracy of measurement are limited by matrix-matched reference materials. In this study, we investigated three new potential reference materials (pyrite NWU-Py, gypsum NWU-Gy and arsenopyrite NWU-Apy) for sulfur isotope ratio analysis by LA-MC-ICP-MS. The ultra-fine powders of pyrite, gypsum and arsenopyrite were synthesized into a solid block using the fast-hot-pressing sintering method (FHP). The reliability of these reference materials was evaluated by large quantities of sulfur isotope measurements by LA-MC-ICP-MS, with mean δ34S values of 3.48 ± 0.26‰ (2SD, n = 787) for NWU-Py, 18.19 ± 0.32‰ (2SD, n = 290) for NWU-Gy, and -0.19 ± 0.32‰ (2SD, n = 383) for NWU-Apy, which are highly consistent with those obtained from isotope ratio mass spectrometry (IRMS). Furthermore, the F-testing and H-index indicate that the three materials have excellent homogeneity of sulfur isotope compositions. Therefore, NWU-Py, NWU-Gy, and NWU-Apy can serve as bracketing matrix-matched reference materials for in situ sulfur isotope measurement by LA-MC-ICP-MS. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) remains the second leading cause of cancerrelated death in women, and the ability to accurately anticipate the presence or absence of lymphovascular space invasion (LVSI) is critical to maintaining optimal patient outcomes. The objective of this study was to establish and verify an MRI radiomics-based model to predict the status of LVSI in patients with operable CC. Methods: The current study performed a retrospective analysis, with 86 patients in the training cohort and 38 patients in the testing group, specifically focusing on patients with CC. The radiomics feature extraction process included ADC, T2WISPAIR, and T2WI sequences. The training group data were used for the initial radionics-based model building, and the model predictive performance was subsequently validated using data from patients recruited in the experimental group. Results: The development of the radiomics scoring model has been completed with 17 selected features. The study found several risk factors associated with LVSI. These risk factors included moderate tumor differentiation (P = 0.005), poor tumor differentiation (P = 0.001), and elevated combined sequence-based radiomics scores (P = 0.001). Radiomics scores based on predictive model, combined sequences, ADC, T2WI-SPAIR, and T2WI exhibited AUCs of 0.897, 0.839, 0.815, 0.698, and 0.739 in the training cohort, respectively, with corresponding testing cohort values of 0.833, 0.833, 0.683, 0.692, and 0.725. Excellent consistency was shown by the calibration curve analysis, which showed a higher degree of agreement between the actual and anticipated LVSI status. Moreover, the decision curve analysis outcomes demonstrated the medical application of this prediction model. Conclusion: This investigation indicated that the MRI radiomics model was successfully developed and validated to predict operable CC patient LVSI status, attaining high overall diagnostic accuracy. However, further external validation and more deeper analysis on a larger sample size are still needed. [ABSTRACT FROM AUTHOR]

Introduction: In patients with pulmonary nodules (PNs), computed tomography (CT)-guided localization is commonly performed prior to the resection of these nodules through video-assisted thoracic surgery (VATS). Aim: To evaluate the relative clinical efficacy of coil and anchored needle (AN) insertion as approaches to preoperative CT-guided PN localization. Material and methods: This single-center, prospective, open-label, randomized controlled trial (registration number: NCT05183945) enrolled consecutive patients from January 2022 to July 2022, assigning these patients at random to undergo either coil or AN localization prior to VATS. Efficacy and safety outcomes in these two groups were then compared. Results: This study enrolled in total 100 patients with 120 PNs who were assigned at random to the coil (patients = 50; PNs = 60) and AN (patients = 50; PNs = 60) localization groups. The respective technical success rates for coil and AN localization were 98.3% (59/60) and 100% (60/60), with no significant difference between the groups (p = 1.000). The coil group had a significantly longer median duration of localization relative to the AN group (16.0 min vs. 8.0 min, p < 0.001). Similar rates of localization-related pneumothorax (8.3% vs. 5.0%, p = 0.715) and pulmonary hemorrhage (5.0% vs. 13.3%, p = 0.110) were observed in both groups. In addition, the VATS resection procedures achieved 100% technical success rates in both of these localization groups. Conclusions: Both coil- and AN-based localization approaches can be successfully employed to localize PNs prior to VATS resection, with the AN localization procedure requiring less time to complete on average as compared to the coil-based approach. [ABSTRACT FROM AUTHOR]

Analyzing sulfur (S) and molybdenum (Mo) isotope ratios in molybdenite, the most common sulfide mineral, is crucial for studying the genesis of ore deposits. However, it is necessary to prepare matrix-matched reference materials for molybdenite. In this study, we employed two different techniques, the high-temperature-high-pressure (HTHP) technique and the rapid hot-pressing technique, to synthesize molybdenites and assessed their suitability as reference materials for in situ Mo and S isotope analysis in molybdenite. The molybdenites synthesized through HTHP and rapid hot-pressing exhibit smooth surfaces and dense structures, making them suitable as reference materials for in situ Mo and S isotope analysis, respectively. These synthesized molybdenites exhibit homogeneous Mo and S isotope compositions based on a large number of LA-MC-ICP-MS measurements. The mean δ98MoNIST SRM 3134 values of 0.70 ± 0.06‰ (n = 4, 2SD) and 0.70 ± 0.05‰ (n = 4, 2SD) determined by solution nebulization MC-ICP-MS are suggested as recommended δ98Mo/95Mo values for Mo-H8 and Mo-P. The mean δ34SV-CDT value of −0.22 ± 0.10‰ (n = 9, 2SD) determined by elemental analyzer isotope ratio mass spectrometry (EA-IRMS) is suggested as a recommended δ34S/32S value for Mo-H8 and Mo-P. Therefore, we recommend combining ultrafine powders with a high-temperature–high-pressure technique and/or a rapid hot-pressing technique to synthesize reference materials for isotopic analysis of other minerals. [ABSTRACT FROM AUTHOR]

In order to effectively improve the seismic and impact resistance performance of soft rock tunnels, a composite support method was proposed and validated in the paper. The UDEC (Universal Distinct Element Code) model of soft rock layers was established, and the movement and subsidence characteristics of the roof and floor of the rock layers under impact loads was simulated and calculated. As a result, a composite support scheme with good cushioning performance was proposed. The top and sides of the tunnel were supported by a combination of anchor rods of different lengths and metal mesh, reinforced by steel beams and vibration absorbing filler around. The anchor rod was designed as a segmented loading structure, and can be set to different preloading forces based on the internal deformation of the rock layer. The dynamic response testing scheme was designed, and the results indicate that the segmented loading anchor rod has a significant buffering effect on the response to impact load, and can provide reasonable tension feedback at different stages. Research has found that when the water cement ratio is 0.5-1.5, the curing efficiency and strength are both higher. In order to compare the seismic performance of composite support and traditional constant resistance anchor rod support, local blasting experiments were conducted. Based on a blasting vibration tester, a data detection and transmission system were designed to obtain the vibration speed of the tunnel roof during the vibration process. The research results show that composite support can reduce the maximum vibration by more than 40 %, stabilize the fragmentation coefficient at 1.38, and have a very significant vibration reduction effect. [ABSTRACT FROM AUTHOR]