MR-tomographischer Befund bei Patienten mit Kniegelenkbeschwerden in Abhängigkeit von der beruflichen und außerberuflichen Gelenkbelastung

Die Gonarthrose als multikausale chronische Erkrankung des Kniegelenks ist die weltweit häufigste Gelenkerkrankung. Ursächlich liegt ein Missverhältnis von Belastbarkeit und mechanischer Beanspruchung des Gelenkknorpels zugrunde, das zur progredienten Schädigung der kartilaginären und ossären Gelenkstrukturen sowie des umgebenden Weichteilmantels führt. Die vorliegende Arbeit untersucht detailliert den MR-tomographischen Befund am Kniegelenk in Abhängigkeit von der Kniebelastung in Beruf und Freizeit. Die Gelenkbelastung wurde individuell im strukturierten Interview mittels eines modifizierten Tegner-Scores erfasst. Es ergeben sich erstmalig Hinweise auf ein belastungskonformes Schadensbild einer durch berufliches Knien und Hocken im Sinne der neuen Berufskrankheit Gonarthrose BK 2112

Edge computing service deployment and task offloading based on multi-task high-dimensional multi-objective optimization

The Mobile Edge Computing (MEC) system located close to the client allows mobile smart devices to offload their computations onto edge servers, enabling them to benefit from low-latency computing services. Both cloud service providers and users seek more comprehensive solutions, necessitating judicious decisions in service deployment and task offloading while balancing multiple objectives. This study investigates service deployment and task offloading challenges in a multi-user environment, framing them as a multi-task high-dimensional multi-objective optimization (MT-HD-MOO) problem within an edge environment. To ensure stable service provisioning, beyond considering latency, energy consumption, and cost as deployment objectives, network reliability is also incorporated. Furthermore, to promote equitable usage of edge servers, load balancing is introduced as a fourth task offloading objective, in addition to latency, energy consumption, and cost. Additionally, this paper designs a MT-HD-MOO algorithm based on a multi-selection strategy to address this model and its solution. By employing diverse selection strategies, an environment selection strategy pool is established to enhance population diversity within the high-dimensional objective space. Ultimately, the algorithm's effectiveness is verified through simulation experiments

The Particle Swarm Optimization Algorithm with Adaptive Chaos Perturbation

Aiming at the two characteristics of premature convergence of particle swarm optimization that the particle velocity approaches 0 and particle swarm congregate, this paper learns from the annealing function of the simulated annealing algorithm and adaptively and dynamically adjusts inertia weights according to the velocity information of particles to avoid approaching 0 untimely. This paper uses the good uniformity of Anderson chaotic mapping and performs chaos perturbation to part of particles based on the information of variance of the population’s fitness to avoid the untimely aggregation of particle swarm. The numerical simulations of five test functions are performed and the results are compared with several swarm intelligence heuristic algorithms. The results shows that the modified algorithm can keep the population diversity well in the middle stage of the iterative process and it can improve the mean best of the algorithm and the success rate of search

Colloidal quantum dots and metal halide perovskite hybridization for solar cells stability and performance enhancement

Metal halide perovskites and colloidal quantum dots (QDs) are two emerging class of photoactive materials that has been attracted considerable attention for next-generation high-performance solution-processed solar cells. In particular, the hybridization of these two materials has been recently demonstrated remarkable performance enhancement due to the complementary nature of the two constituents. In this review, we will highlight the recent progress of QDs and perovskite hybridization in solar cell applications. More specifically, the unique properties of monophase perovskite QDs will be summarised which are demonstrated by homogeneously hybridizing perovskite QDs into perovskite lattice. We also discuss the recent progress in heterogeneously hybridizing discrete colloidal QDs into perovskite layers which exhibit significant perovskite film stability enhancement as well as corresponding solar cell performance improvement. PbS QDs, other chalcogenides QDs, as well as emerging two-dimensional QDs, are further accounted through multiple methods, such as bilayer architectures, core-shell structures or blending multiple QDs into perovskite layers. In the end, an outlook perspective of this field has been proposed to point out several challenges and possible solutions

Ensemble learning enhances the precision of preliminary detection of primary hepatocellular carcinoma based on serological and demographic indices

Primary hepatocellular carcinoma (PHC) is associated with high rates of morbidity and malignancy in China and throughout the world. In clinical practice, a combination of ultrasound and alpha-fetoprotein (AFP) measurement is frequently employed for initial screening. However, the accuracy of this approach often falls short of the desired standard. Consequently, this study aimed to investigate the enhancement of precision of preliminary detection of PHC by ensemble learning techniques. To achieve this, 712 patients with PHC and 1887 healthy controls were enrolled for the assessment of four ensemble learning methods, namely, Random Forest (RF), LightGBM, Xgboost, and Catboost. A total of eleven characteristics, comprising nine serological indices and two demographic indices, were selected from the participants for use in detecting PHC. The findings identified an optimal feature subset consisting of eight features, namely AFP, albumin (ALB), alanine aminotransferase (ALT), platelets (PLT), age, alkaline phosphatase (ALP), hemoglobin (Hb), and body mass index (BMI), that achieved the highest classification accuracy of 96.62%. This emphasizes the importance of the collective use of these features in PHC diagnosis. In conclusion, the results provide evidence that the integration of serological and demographic indices together with ensemble learning models, can contribute to the precision of preliminary diagnosis of PHC

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

ObjectivesTo provide an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) of the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of extensive-stage small-cell lung cancer (ES-SCLC).MethodsPubMed, Web of Science, Embase, Clinicaltrials and the Cochrane Library were systematically searched to extract RCTs concerning the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of ES-SCLC from the time of database inception to October 31, 2022. The literature was independently selected, information was extracted and the risk of bias of the RCTs was evaluated according to the inclusion and exclusion criteria. Stata14.0 was used for the meta-analysis.ResultsSix studies involving 2,600 patients were included in the analysis. The results of the meta-analysis showed that the combination of PD-1/PD-L1 inhibitors significantly improved the OS (HR: 0.73, 95% CI: 0.66-0.80; P<0.0001), prolonged PFS (HR: 0.66,95% CI: 0.55-0.79; P<0.0001) and did not increase overall incidence of treatment-related adverse events (TRAEs) (RR: 1.03, 95% CI: 0.97-1.09; P=0.330) in ES-SCLC patients compared with chemotherapy alone. The subgroup analysis found that patients with negative PD-L1 expression (< 1%) benefited in OS, whereas patients with positive PD-L1 expression (≥1%) had no statistically significant difference in OS. There was a statistically significant difference in PFS between PD-L1-negative (< 1%) and PD-L1-positive (≥1%) patients. The addition of a PD-1 inhibitor or PD-L1 inhibitor to the chemotherapy regimen can improve OS and prolong PFS in patients with ES-SCLC.ConclusionsPD-1/PD-L1 inhibitors combination chemotherapy significantly improves PFS and OS in ES-SCLC patients without increasing the overall incidence of TRAEs

Establishment of predictive nomogram and web-based survival risk calculator for desmoplastic small round cell tumor: A propensity score-adjusted, population-based study

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study’s objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times: 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy

APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b

Increasing evidence suggests different, not completely understood roles of microRNA biogenesis in the development and progression of lung cancer. The overexpression of the DNA repair protein apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an important cause of poor chemotherapeutic response in lung cancer and its involvement in onco-miRNAs biogenesis has been recently described. Whether APE1 regulates miRNAs acting as prognostic biomarkers of lung cancer has not been investigated, yet. In this study, we analyzed miRNAs differential expression upon APE1 depletion in the A549 lung cancer cell line using high-throughput methods. We defined a signature of 13 miRNAs that strongly correlate with APE1 expression in human lung cancer: miR-1246, miR-4488, miR-24, miR-183, miR-660, miR-130b, miR-543, miR-200c, miR-376c, miR-218, miR-146a, miR-92b and miR-33a. Functional enrichment analysis of this signature revealed its biological relevance in cancer cell proliferation and survival. We validated DICER1 as a direct functional target of the APE1-regulated miRNA-33a-5p and miR-130b-3p. Importantly, IHC analyses of different human tumors confirmed a negative correlation existing between APE1 and Dicer1 protein levels. DICER1 downregulation represents a prognostic marker of cancer development but the mechanisms at the basis of this phenomenon are still completely unknown. Our findings, suggesting that APE1 modulates DICER1 expression via miR-33a and miR-130b, reveal new mechanistic insights on DICER1 regulation, which are of relevance in lung cancer chemoresistance and cancer invasiveness

Inhibition of Cyclin D1 Expression in Human Glioblastoma Cells is Associated with Increased Temozolomide Chemosensitivity

Background/Aims: Cyclin D1 (CCND1) is frequently overexpressed in malignant gliomas. We have previously shown ectopic overexpression of CCND1 in human malignant gliomas cell lines. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blot (WB) was performed to investigate the expression of CCND1 in glioma tissues and cell lines. The biological function of CCND1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. Results: Here we reported that CCND1 expression was positively associated with the pathological grade and proliferative activity of astrocytomas, as the lowest expression was found in normal brain tissue (N = 3) whereas the highest expression was in high-grade glioma tissue (N = 25). Additionally, we found that the expression level of CCND1 was associated with IC50 values in malignant glioma cell lines. Forced inhibition of CCND1 increased temozolomide efficacy in U251 and SHG-44 cells. After CCND1 overexpression, the temozolomide efficacy decreased in U251 and SHG-44 cells. Colony survival assay and apoptosis analysis confirmed that CCND1 inhibition renders cells more sensitive to temozolomide treatment and temozolomide-induced apoptosis in U251 and SHG-44 cells. Inhibition of P-gp (MDR1) by Tariquidar overcomes the effects of CCND1 overexpression on inhibiting temozolomide-induced apoptosis. Inhibition of CCND1 inhibited cell growth in vitro and in vivo significantly more effectively after temozolomide treatments than single temozolomide treatments. Finally, inhibition of CCND1 in glioma cells reduced tumor volume in a murine model. Conclusion: Taken together, these data indicate that CCND1 overexpression upregulate P-gp and induces chemoresistance in human malignant gliomas cells and that inhibition of CCND1 may be an effective means of overcoming CCND1 associated chemoresistance in human malignant glioma cells

S1P/S1PR signaling pathway advancements in autoimmune diseases

Sphingosine-1-phosphate (S1P) is a versatile sphingolipid that is generated through the phosphorylation of sphingosine by sphingosine kinase (SPHK). S1P exerts its functional effects by binding to the G protein-coupled S1P receptor (S1PR). This lipid mediator plays a pivotal role in various cellular activities. The S1P/S1PR signaling pathway is implicated in the pathogenesis of immune-mediated diseases, significantly contributing to the functioning of the immune system. It plays a crucial role in diverse physiological and pathophysiological processes, including cell survival, proliferation, migration, immune cell recruitment, synthesis of inflammatory mediators, and the formation of lymphatic and blood vessels. However, the full extent of the involvement of this signaling pathway in the development of autoimmune diseases remains to be fully elucidated. Therefore, this study aims to comprehensively review recent research on the S1P/S1PR axis in diseases related to autoimmunity