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BackgroundOsteoporosis(OP) is a systemic bone disease that leads to a decrease in bone mineral density(BMD), thus increasing the susceptibility to brittle fractures[1]. Epidemiological studies indicate a confirmed correlation between osteoporosis and cardiovascular disease (CVD)[2]. BMD as a risk factor for CVD events and death can better predict the development of lesions than traditional risk factors such as hyperlipidemia and smoking. However, observational studies may be influenced by potential confounders. At the same time, the Mendel randomization (MR) study can overcome these confounding factors to evaluate causality.ObjectivesThis study aimed to evaluate the genetic correlation between OP and CVD through bi-directional MR and provide a new strategy for clinical prevention, treatment, and nursing of OP and CVD.MethodsWe selected three different sites[femoral neck bone mineral density (FN BMD), forearm BMD(FA BMD) and lumbar spine BMD (LS BMD)] from the GEnetic Factors for OSteoporosis (GEFOS) and heel BMD(eBMD) from UK biobank datasets as the phenotype of OP. The instrumental variables(IVs) of the whole genome significance level related to the 12 CVDs were from the published summary statistics. IVW was selected as the primary analytical method to evaluate the causal relationship between exposure and results because it provides the most convincing estimate when the directional multidirectional nature of IV is missing. Outlier variants identified by MR-PRESSO were removed to reduce heterogeneity and the effect of horizontal pleiotropy. To confirm the stability, we performed a “leave-one-out” approach for the sensitivity analysis.ResultsLS-BMD had a direct causal relationship with myocardial infarction(MI) and coronary heart disease(CHD)[MI-related analysis: odds ratio (OR) = 1.101, 95% confidence interval (CI) = (1.033,1.174), p = 0.003; CHD-related analysis: OR (95% CI) = 1.105 (1.043,1.170), p = 0.001]. FN BMD will increase the risk of large-artery atherosclerotic stroke(LAS), small-vessel stroke(SVS), coronary artery disease(CAD) and CHD[LAS-related analysis: OR (95% CI) = 1.152 (1.014,1.308), p = 0.029; SVS-related analysis: OR (95% CI) = 1.139 (1.015,1.128), p = 0.026; CAD-related analysis: OR (95% CI) = 1.088 (1.023,1.056), p = 0.007; CHD-related analysis: OR (95% CI) = 1.086 (1.023,1.154), p = 0.007]. At the same time, SVS, cardioembolic stroke(CES) and any stroke(AS) will increase the possibility of FN BMD[SVS-related analysis: OR (95% CI) = 1.051 (1.006,1.095), p = 0.024; CES-related analysis: OR (95% CI) = 1.034 (1.006,1.063), p = 0.018; AS-related analysis: OR (95% CI) = 1.074 (1.020,1.131), p = 0.006].ConclusionOP and CVD might mutually have a significant causal effect on each other. Our results supported the view that increased BMD is more likely to lead to cardiovascular events, and stroke may lead to increased FN BND.References[1]Ivanova, S., Vasileva, L., Ivanova, S., Peikova, L. & Obreshkova, D. Osteoporosis: Therapeutic Options. Folia Med (Plovdiv) 57, 181-190, doi:10.1515/folmed-2015-0037 (2015).[2]Tremollieres, F. & Ribot, C. Bone mineral density and prediction of non-osteoporotic disease. Maturitas 65, 348-351, doi:10.1016/j.maturitas.2009.12.023 (2010).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Crohn's disease (CD) is a chronic inflammatory disease of unknown etiology. The IL-23/IL-17 pathway plays an essential role in the pathogenesis of CD. More and more approved IL-23 inhibitors are being used for the treatment of CD. However, no studies have systematically compared and evaluated the efficacy of these IL-23 inhibitors. This study aims to compare the efficacy of various IL-23 inhibitors(Brazikumab, Guselkumab, Mirikizumab, Risankizumab, and Ustekinumab) for treating Crohn's disease by conducting a Bayesian network meta-analysis (NMA). We searched the database, including PubMed, Embase, Web of Science, Cochrane Library, MEDLINE, and Web of Science, Clinical Trials. gov, (from inception until February 5, 2023). Efficacy (Clinic response, Clinic remission, Endep remission, and C-reactive protein) were compared using a Bayesian NMA. Results were presented as the pooled estimates of odds ratios (ORs) or weighted mean difference (WMD) (95% CI). The random-effects model was selected to synthesize the data. The ranking probability for each IL-23 inhibitor was evaluated using the surface under the cumulative ranking curves (SUCRA). The larger the SUCRA value, the better the rank of the intervention. The global inconsistency was evaluated by comparing the fit of consistency and inconsistency models, where P ≤ 0.05 indicated inconsistency. All analyses were conducted using the gemtc package of R (version 4.2.2). In terms of Clinic response, a total of 40 studies were included. The NMA showed that Brazikumab combined with Guselkumab [OR=-0.98, 95% (CI, -2.9, 0.91)], PBO(PBO) combined with Risankizumab [OR=-0.54, 95% (CI, -1.16, 0.18)], PBO combined with Ustekinumab [OR=-1.38, 95% (CI, -2.77, -0.01)], Risankizumab combined with Ustekinumab [OR=-0.84, 95% (CI, -2.43, 0.63)]. According to SUCRA, Ustekinumab (78.9%), Risankizumab (52.2%), PBO(23.6%), Mirikizumab(34%), Guselkumab (87.6%), and Brazikumab (23.6%). For clinic remission, the result of NMA showed that Brazikumab combined with Guselkumab [OR=-1.59, 95% (CI, -3.78, 0.59)], Brazikumab combined with Ustekinumab [OR=-1.37, 95% (CI, -3.57, 0.83)], PBO combined with Risankizumab [OR=-0.47, 95% (CI, -1.19, 0.34)], PBO combined with Ustekinumab [OR=-1.26, 95% (CI, -2.86, 0.33)], Risankizumab combined with Ustekinumab [OR=-0.8, 95% (CI, -2.6, 0.93)]. According to SUCRA, Ustekinumab (79.3%), Risankizumab (53.7%), PBO(22.1%), Mirikizumab(33.4%), Guselkumab (90.3%)and Brazikumab (21.7%) (Figure 1). In terms of efficacy alone, Guselkumab ranked first among all IL-23 inhibitors, followed by Ustekinumab, and all had significantly different clinical remission rates than patients in the PBO group, while the remaining drugs were less effective than PBO. [Display omitted] NIL. NIL. None Declared.

BackgroundPsoriatic arthritis (PsA) is a chronic autoimmune disease that is seen in nearly 30% of patients with psoriasis. As a new targeted treatment drug, risanzumab may provide a new treatment with fewer side effects for patients with psoriasis arthritis. However, there are currently discrepancies in the evaluation of the efficacy of Risankizumab in PsA patients.ObjectivesThis study aims to systematically evaluate the efficacy of Risankizumabin patients with PsA.MethodsWe systematically searched PubMed, Embase, Web of Science, Cochrane Library, MEDLINE, Web of Knowledge, Clinical Trials. gov, FDA. gov and print databases (SSRN, bioRxiv, and MedRxiv) from the establishment of the database to January 2, 2023, and conducted data analysis in Stata 12.0. We used the I-squared (I2) to assess the heterogeneity of the included studies in order to select the appropriate model for statistical analysis. A random-effects model will be used when I2>50%, otherwise, a fixed-effect model will be applied. The publication bias was evaluated by using Egger test.ResultsWe ultimately included 11 studies that included data on six outcome indexes. The results of the meta-analysis of ACR20 as our main outcome indicator of interest showed patients in the Risankizumab group had a significantly higher ACR20 response rate than those in the placebo group at 24 weeks [RR=1.768, 95%CI (1.572, 1.988), P<0.001]. In addition, compared with the placebo group, the MDA response rate of Risankizumab group significantly higher [RR=1.841, 95%CI 1.084-3.126, P<0.05]. Then, SF-36 score [SMD=0.508, 95%CI (0.337, 0.678), P<0.001] were improved in the Risankizumab group, which was statistically significantly different from the placebo group. For HAQ-DI, the Risankizumab group had significantly lower scores than the placebo group[SMD=-0.273, 95%CI (0.373, 0.172), P<0.001]. However, FACIT-F scores in the Risankizumab group were significantly higher than placebo group [SMD=0.270, 95%CI (0.177, 0.364), P<0.001]. For PASI, patients had an average reduction of 9.8 points after Risankizumab treatment [MD=-9.832, 95%CI (14.367, 5.298), P<0.001]. (Figure 1)ConclusionThe overall results of the meta-analysis show that Risankizumab treatment can significantly improve the symptoms of PsA such as arthritis and skin symptoms, improve the clinical remission rate and the quality of life of patients. However, taking Risankizumab may also potentially increase fatigue levels in patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundPsoriasis is a common chronic inflammatory disease of the skin[1]. The IL-23/IL-17 immune pathway plays a vital role in promoting Psoriasis pathogenesis[2]. Tildrakizumab, a humanized IgG1 monoclonal antibody against interleukin 23 p19, is currently used in the treatment of patients with psoriasis.ObjectivesThis study aimed to evaluate the efficacy of tildrakizumab in the treatment of psoriasis.MethodsFive databases, including PubMed, Embase, Medline, Web of Science, and Cochrane Library, were retrieved from their establishment to January 2, 2023. We used the EndNote X9 software to filter the retrieved articles according to the inclusion and exclusion criteria. Heterogeneity was tested using I-squared (I2). When I2>50%, we choosed the random effects model for data analysis, conversely, a fixed effects model. Publication bias was assessed using the Egger test. All analyzes were performed in STATA 12.0.ResultsWe included 6 studies, 2,395 patients in the Tildrakizumab group and 552 patients in the placebo group (Table 1). Results of the meta-analysis showed that 68% of patients with psoriasis met the PAIS75 remission criteria after taking Tildrakizumab [Rate =0.68 95%CI(0.66, 0.70), P<0.001], and they had significantly higher PASI75 response rates than the placebo group [RR=11.390, 95%CI (8.08, 16.06), P<0.001]. Compared to the placebo group, patients in the Tildrakizumab group had a significantly higher remission rate of PASI90 [RR=26.751, 95%CI (15.282,46.827), P<0.001]. In addition, patients taking Tildrakizumab had an average 15-point reduction in PASI scores [Rate=-14.854 95%CI(-19.146, -10.561), P<0.001], and 45% of patients achieved PASI100 remission criteria [Rate= 0.450, 95%CI (0.131, 0.769), P=0.006] (Figure 1).ConclusionThis study showed that Tildrakizumab improved disease activity and increased clinical remission rates in patients with psoriasis, demonstrating a better therapeutic effect.References[1]Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis. Lancet 2021; 397 (10281): 1301-1315. doi: 10.1016/s0140-6736(20)32549-6.[2]Blauvelt A, Chiricozzi A. The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis. Clin Rev Allergy Immunol 2018; 55 (3): 379-390. doi: 10.1007/s12016-018-8702-3.Table 1.Population characteristics included in the studyAuthor(Year)Population (include in analysis)Age (Mean±SD)Gender (male %)TILPBOTILPBOTILPBOKristian Reich(2017)617(617)155(154)46.65±13.1447.9±13.570.264.5K. Papp(2015)309(102)46(41)44.79±13.0445.9±11.775.182.5Alessandra Narcisi.(2022)237(121)NA48.6±14.6NA59.9NAY Poulin(2020)1413(1413)357(357)NA72.170.0Cantrell, W.(2021)248(135)NANANAT Graier(2022)15(7)NA45.9±14.1NA73.3NAAcknowledgements:NIL.Disclosure of InterestsNone Declared.

In this paper, we present a groupwise graph-theory-based parcellation approach to define nodes for network analysis. The application of network-theory-based analysis to extend the utility of functional MRI has recently received increased attention. Such analyses require first and foremost a reasonable definition of a set of nodes as input to the network analysis. To date many applications have used existing atlases based on cytoarchitecture, task-based fMRI activations, or anatomic delineations. A potential pitfall in using such atlases is that the mean timecourse of a node may not represent any of the constituent timecourses if different functional areas are included within a single node. The proposed approach involves a groupwise optimization that ensures functional homogeneity within each subunit and that these definitions are consistent at the group level. Parcellation reproducibility of each subunit is computed across multiple groups of healthy volunteers and is demonstrated to be high. Issues related to the selection of appropriate number of nodes in the brain are considered. Within typical parameters of fMRI resolution, parcellation results are shown for a total of 100, 200, and 300 subunits. Such parcellations may ultimately serve as a functional atlas for fMRI and as such three atlases at the 100-, 200- and 300-parcellation levels derived from 79 healthy normal volunteers are made freely available online along with tools to interface this atlas with SPM, BioImage Suite and other analysis packages. [Display omitted] •Resting-state connectivity data parcellated using graph theory approach.•Yields groupwise whole-brain parcellation of the order of 300 nodes•Uniform timecourses within nodes•Ideal for network analysis of functional connectivity•Functional atlas available online

Photon-enhanced thermionic emission is a method of solar-energy conversion that promises to combine photon and thermal processes into a single mechanism, overcoming fundamental limits on the efficiency of photovoltaic cells. Photon-enhanced thermionic emission relies on vacuum emission of photoexcited electrons that are in thermal equilibrium with a semiconductor lattice, avoiding challenging non-equilibrium requirements and exotic material properties. However, although previous work demonstrated the photon-enhanced thermionic emission effect, efficiency has until now remained very low. Here we describe electron-emission measurements on a GaAs/AlGaAs heterostructure that introduces an internal interface, decoupling the basic physics of photon-enhanced thermionic emission from the vacuum emission process. Quantum efficiencies are dramatically higher than in previous experiments because of low interface recombination and are projected to increase another order of magnitude with more stable, low work-function coatings. The results highlight the effectiveness of the photon-enhanced thermionic emission process and demonstrate that efficient photon-enhanced thermionic emission is achievable, a key step towards realistic photon-enhanced thermionic emission based energy conversion. By having the electrons and lattice at high temperature, photon-enhanced thermionic emission offers improved electron extraction energy in solar conversion devices. Schwede et al. use a heterostructure design to introduce an internal interface, showing higher quantum efficiencies than previous experiments.

Resting-state fMRI provides a method to examine the functional network of the brain under spontaneous fluctuations. A number of studies have proposed using resting-state BOLD data to parcellate the brain into functional subunits. In this work, we present two state-of-the-art graph-based partitioning approaches, and investigate their application to the problem of brain network segmentation using resting-state fMRI. The two approaches, the normalized cut (Ncut) and the modularity detection algorithm, are also compared to the Gaussian mixture model (GMM) approach. We show that the Ncut approach performs consistently better than the modularity detection approach, and it also outperforms the GMM approach for in vivo fMRI data. Resting-state fMRI data were acquired from 43 healthy subjects, and the Ncut algorithm was used to parcellate several different cortical regions of interest. The group-wise delineation of the functional subunits based on resting-state fMRI was highly consistent with the parcellation results from two task-based fMRI studies (one with 18 subjects and the other with 20 subjects). The findings suggest that whole-brain parcellation of the cortex using resting-state fMRI is feasible, and that the Ncut algorithm provides the appropriate technique for this task.

To address the question of whether established or experimental anticancer chemotherapeutics can exert their cytotoxic effects by autophagy, we performed a high-content screen on a set of cytotoxic agents. We simultaneously determined parameters of autophagy, apoptosis and necrosis on cells exposed to ∼1400 compounds. Many agents induced a ‘pure’ autophagic, apoptotic or necrotic phenotype, whereas less than 100 simultaneously induced autophagy, apoptosis and necrosis. A systematic analysis of the autophagic flux induced by the most potent 80 inducers of GFP-LC3 puncta among the NCI panel agents showed that 59 among them truly induced autophagy. The remaining 21 compounds were potent inducers of apoptosis or necrosis, yet failed to stimulate an autophagic flux, which were characterized as microtubule inhibitors. Knockdown of ATG7 was efficient in preventing GFP-LC3 puncta, yet failed to attenuate cell death by the agents that induce GFP-LC3 puncta. Thus there is not a single compound that would induce cell death by autophagy in our screening, underscoring the idea that cell death is rarely, if ever, executed by autophagy in human cells.

Background fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. Methods fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N  = 23) and ASD-negative (HLN, N  = 91), and low-likelihood ASD-negative (LLN, N  = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. Results OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices ( p  = 0.012), but none for HLP versus HLN ( p  = 0.047) nor HLN versus LLN ( p  = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)– temporal default mode network (tDMN) pair ( p  = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN ( p  = 0.0461 and 0.0004). HLP did not differ from HLN ( p  = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN ( p  = 0.0036). Conclusions 24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.

Quantum cascade (QC) lasers operating in the mid-infrared (IR) are being intensely pursued for environmental sensing and other important technological applications. Having demonstrated mid-IR (3  μ m to 5  μ m) electroluminescence (EL) from a II–VI intersubband device based on wide-band-gap (2.9 eV) Zn 0.24 Cd 0.26 Mg 0.5 Se on InP, there has been a drive towards production of a QC laser from these materials. To achieve lasing, waveguiding layers that straddle the active region used in the EL structure must be included. Initial attempts to grow this more complex structure resulted in degradation of the material quality. This paper presents the optimization steps required for the growth of the full QC laser structure and discusses possible mechanisms for the degraded quality.