Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and Prognostic Value of CD80 and CD86 in the Tumor Microenvironment of Newly Diagnosed Glioblastoma

ABSTRACT: Background: Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas (GBMs). Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in GBM microenvironment are still unclear. Methods: In this study, we investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. Furthermore, CD80 and CD86 at the protein level were investigated in the discovery cohort. Results: Both CD80 and CD86 are expressed heterogeneously in the TME at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both local OncoNeuroTek dataset and TCGA datasets. CD80 and CD86 mRNA high expression was significantly associated with shorter progression free survival (PFS) (p < 0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p < 0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p < 0.05). Conclusion: CD86 could be used as a potential biomarker for the prognosis of GBM patients treated with immunotherapy; however, additional studies are needed to validate these findings.
Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells

Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration ([Ca2+]i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca2+]i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced [Ca2+]i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.
Identification of Aging-Related Genes Associated with Prognostic Value and Immune Microenvironment Characteristics in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a complex invasive tumour that occurs mainly among the elderly. Therefore, we analysed the relationship between ageing-related genes (AG) and DLBCL prognosis. Datasets related to DLBCL and human AGs were downloaded and screened from the Gene Expression Omnibus (GEO) database and HAGR website, respectively. LASSO and Cox regression were used to analyse AGs in the dataset and construct an AG predictive model related to DLBCL prognosis. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment were used to analyse the function of the AG predictive model. The immune microenvironment and immune cell infiltration in DLBCL and their relationship with the AG prediction model were also analysed. After the analysis, 118 AGs were identified as genes related to DLBCL prognosis. Using the LASSO and Cox regression analyses, 9 AGs (PLAU, IL7R, MYC, S100B, IGFBP3, NR3C1, PTK2, TBP, and CLOCK) were used to construct an AG prognostic model. In the training and verification sets, this model exhibited excellent predictive ability for the prognosis of patients with DLBCL who have different clinical characteristics. Further analysis revealed that the high- and low-risk groups of the AG prognostic model were significantly correlated with immune cell infiltration and tumour microenvironment in DLBCL. Functional enrichment analysis also showed that the genes in the AG model were associated with immune-related functions and pathways. In conclusion, we constructed an AG model with a strong predictive function in DLBCL, with the ability to predict the prognosis of patients with different clinical features. This model provides new ideas and potential therapeutic targets for the study of the pathogenesis of DLBCL.
Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant

(1) Introduction: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety. (2) Methods: We conducted a retrospective study of HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between 1 April 2016 and 31 January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up. (3) Results: We included 200 HM patients with IFIs that were classified as definite (11), probable (63) and possible (126). Aspergillus spp was the most commonly isolated pathogen. The majority of patients (59%) received prophylaxis with anti-mold therapy and Isavuconazole was used as a primary therapy in 43% of patients, and as salvage therapy in 58%. The switch to Isavuconazole was driven by the failure of the primary therapy in 66% of the cases and by adverse effects in 29%. Isavuconazole was used as monotherapy in 30% of the cases and in combination in 70%. Adverse events possibly related to Isavuconazole were reported in eight patients (4%) leading to drug discontinuation. Moreover, a favorable response with Isavuconazole was observed in 40% at 6 weeks and in 60% at 12 weeks. There was no significant difference between isavuconazole monotherapy and combination therapy (p = 0.16 at 6 weeks and p = 0.06 at 12 weeks). Finally, there was no significant difference in outcome when Isavuconazole was used after failure of other anti-mold prophylaxis or treatment versus when used de novo as an anti-mold therapy (p = 0.68 at 6 weeks and p = 0.25 at 12 weeks). (4) Conclusions: Whether used as first-line therapy or after the failure of other azole and non-azole prophylaxis or therapies, isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high-risk cancer patients with hematologic malignancies. Moreover, combination therapy did not improve the outcome compared to Isavuconazole therapy.
The Association between Helicobacter Pylori Infection and Abdominal Pain in Children Aged 2-10 Years

Background: Helicobacter pylori (H. Pylori) is a common infection in children, especially in the developing countries. The infection is usually asymptomatic but it may cause gastrointestinal diseases. In children, the symptoms include abdominal pain, vomiting and anemia. Recurrent abdominal pain (RAP) is a common cause of children’s referral. But, whether H. Pylori causes RAP in children has to be scrutinized to prevent further complications by proper diagnosis and treatment. However, there is still controversy in the literature regarding this issue. Therefore, we aimed to assess the association between H. Pylori and RAP in children. Materials and Methods: In this case-control study, the children with RAP aged 2-10 years who referred to a private pediatric clinic in Marvdasht, Iran, were compared to other children without RAP, during 2015. The sample size was calculated to be 70 for each case and the control group. The patients were visited by a gastro-enterologist who recorded the demographic data of all the patients and the findings of stool test for H. Pylori. To assess the association of RAP with H. Pylori, the odds ratio was calculated. The statistical analysis was performed using SPSS 20.0 software. The P-values less than 0.05 were considered as statistically significant. Results: The mean age of the participants was 7.35±3.11 (with a range of 2-10). In the case group, 41/70 and 69/70 of the control group were girls. H. Pylori was found positive in 37 cases (52.9%) of the case group and 11 (15.7%) in the control group (P<0.001, OR=6.01, 95% CI=2.71-13.34). Logistic regression with adjustment for age indicated that there was a positive association between positive H. Pylori and abdominal pain (OR=16.69, 95% CI=4.71-59.18). This model also showed that by adjusting the H. Pylori test result, age was also positively associated with abdominal pain (OR=0.27, 95% CI=0.18-0.45). A T-test also indicated that the mean titer of H. Pylori was significantly higher in case group (1.42±1.29) than the control group (0.86±1.52) (P=0.020). Conclusion: There was a statistically significant correlation between H. Pylori and RAP. [GMJ. 2016;5(1):19-24]
Microorganismal Cues Involved in Host-Location in Asilidae Parasitoids

Simple Summary This research shows how symbionts mediate orientation to hosts in a dipteran parasitoid system. We show that two close related species use cues located in different parts of the host. This study increases our knowledge of Mallophora species and sheds light on adaptations they have when adopting a parasitoid lifestyle. Abstract Parasitoids are organisms that kill their host before completing their development. Typical parasitoids belong to Hymenoptera, whose females search for the hosts. But some atypical Diptera parasitoids also have searching larvae that must orientate toward, encounter, and accept hosts, through cues with different levels of detectability. In this work, the chemical cues involved in the detection of the host by parasitoid larvae of the genus Mallophora are shown with a behavioral approach. Through olfactometry assays, we show that two species of Mallophora orient to different host species and that chemical cues are produced by microorganisms. We also show that treating potential hosts with antibiotics reduces attractiveness on M. ruficauda but not to M. bigoti suggesting that endosymbiotic bacteria responsible for the host cues production should be located in different parts of the host. In fact, we were able to show that M. bigoti is attracted to frass from the most common host. Additionally, we evaluated host orientation under a context of interspecific competence and found that both parasitoid species orient to Cyclocephaala signaticollis showing that host competition could occur in the field. Our work shows how microorganisms mediate orientation to hosts but differences in their activity or location in the host result in differences in the attractiveness of different cues. We show for the first time that M. bigoti behaves similar to M. ruficauda extending and reinforcing that all Mallophora species have adopted a parasitoid lifestyle.
Precision and Advanced Nano-Phytopharmaceuticals for Therapeutic Applications

Phytopharmaceuticals have been widely used globally since ancient times and acknowledged by healthcare professionals and patients for their superior therapeutic value and fewer side-effects compared to modern medicines. However, phytopharmaceuticals need a scientific and methodical approach to deliver their components and thereby improve patient compliance and treatment adherence. Dose reduction, improved bioavailability, receptor selective binding, and targeted delivery of phytopharmaceuticals can be likely achieved by molding them into specific nano-formulations. In recent decades, nanotechnology-based phytopharmaceuticals have emerged as potential therapeutic candidates for the treatment of various communicable and non-communicable diseases. Nanotechnology combined with phytopharmaceuticals broadens the therapeutic perspective and overcomes problems associated with plant medicine. The current review highlights the therapeutic application of various nano-phytopharmaceuticals in neurological, cardiovascular, pulmonary, and gastro-intestinal disorders. We conclude that nano-phytopharmaceuticals emerge as promising therapeutics for many pathological conditions with good compliance and higher acceptance.
Decentralised adaptive fuzzy event-triggered control for nonlinear switched large-scale systems with unknown backlash-like hysteresis

A decentralised adaptive fuzzy event-triggered control problem of nonlinear switched large-scale systems with unknown hysteresis is investigated in this article, in which the unknown hysteresis is expressed by several nonlinear differential equations. The unknown nonlinearities in the systems are generally approximated by fuzzy logic systems due to their excellent function approximation abilities. Through employing dynamic surface control technology, the issue of complexity explosion resulting from repeated differentiation in the traditional backstepping method is overcome. A decentralised event-triggered controller is developed through adopting the common Lyapunov function approach. In the closed-loop system, the whole signals are semi-globally uniformly ultimately bounded which can be guaranteed through adopting the proposed scheme. Ultimately, the simulation results of two examples demonstrate the validity of the proposed strategy.
Computational Investigation of a Novel Box-Wing Aircraft Concept

With regard to the current needs for greener aviation, this study focuses on a novel concept of Box-Wing Aircraft (BWA). Labelled SmartLiner (BWA/SL), this conceptual aircraft comes as a triplane comprising backward and forward swept wings. The aerodynamic performance and structural characteristics of this BWA/SL aircraft are here explored through numerical simulation, using Computational Fluid Dynamics (CFD) and Fluid-Structure Interaction (FSI). The computational approach is first validated using NASA’s Common Research Model (CRM) aircraft, which is then taken as a reference solution against which to compare the aero-structural merits of the BWA/SL concept. Results show that, although its design is still preliminary and lacks optimization, the BWA/SL aircraft exhibits very decent aerodynamic performance, with higher lifting capacities and a reasonable lift-to-drag ratio. Moreover, thanks to the closed frame of its peculiar planform, it demonstrates superior structural characteristics, including under extreme loading scenarios. Based on this preliminary analysis and considering the room left for its further optimization, this conceptual aircraft thus appears as a potentially promising alternative for the development of more environmentally friendly airliners.
EFFECT OF INCREASING MEASUREMENT DURATION ON 'ACCURACY' OF WHOLE-BODY VIBRATION FIELD MEASUREMENTS

When searching the literature, one is hard pressed to find reports of whole-body vibration measurements with a duration longer than a few minutes. When making a risk assessment according to standards and directives, the vibration exposure must be assessed and often measured. It has previously been assumed that a measurement of a few minutes will suffice as being representative of the full working day, although there little evidence to back-up this assumption. This paper presents measures of vibration exposure for drivers that were made for a full working day. Using a simple model, the exposures were analysed to investigate the potential errors from making measurements from 10 seconds to 60 minutes when compared with the full working day exposure. It is recommended that measurements of vertical whole-body vibration in vehicles should last at least 10 minutes.
The Effect of Wind Stress on Seasonal Sea-Level Change on the Northwestern European Shelf

Projections of relative sea-level change (RSLC) are commonly reported at an annual mean basis. The seasonality of RSLC is often not considered, even though it may modulate the impacts of annual mean RSLC. Here, we study seasonal differences in 21st-century ocean dynamic sea-level change (DSLC, 2081-2100 minus 1995-2014) on the Northwestern European Shelf (NWES) and their drivers, using an ensemble of 33 CMIP6 models complemented with experiments performed with a regional ocean model. For the high-end emissions scenario SSP5-8.5, we find substantial seasonal differences in ensemble mean DSLC, especially in the southeastern North Sea. For example, at Esbjerg (Denmark), winter mean DSLC is on average 8.4 cm higher than summer mean DSLC. Along all coasts on the NWES, DSLC is higher in winter and spring than in summer and autumn. For the low-end emissions scenario SSP1-2.6, these seasonal differences are smaller. Our experiments indicate that the changes in winter and summer sea-level anomalies are mainly driven by regional changes in wind-stress anomalies, which are generally southwesterly and east-northeasterly over the NWES, respectively. In spring and autumn, regional wind-stress changes play a smaller role. We also show that CMIP6 models not resolving currents through the English Channel cannot accurately simulate the effect of seasonal wind-stress changes on he NWES. Our results imply that using projections of annual mean RSLC may underestimate the projected changes in extreme coastal sea levels in spring and winter. Additionally, changes in the seasonal sea-level cycle may affect groundwater dynamics and the inundation characteristics of intertidal ecosystems.
Position and Orientation Tunnel-Following NMPC of Robot Manipulators Based on Symbolic Linearization in Sequential Convex Quadratic Programming

The tunnel-following nonlinear model predictive control (NMPC) scheme allows to exploit acceptable deviations around a path reference. This is done by using convex-over-nonlinear functions as objective and constraints in the underlying optimal control problem (OCP). The convex-over-nonlinear structure is exploited by algorithms such as the generalized Gauss-Newton (GGN) method or the sequential convex quadratic programming (SCQP) method to reduce the computational complexity of the OCP solution. However, the engineering time required to implement these methods is high. We address the problem of reducing the engineering time in the implementation of SCQP, focusing on a standard sequential quadratic programming (SQP) implementation where symbolic linearization is applied to the nonlinear part of the convex-over-nonlinear functions in the objective and constraints. The novelty of this paper is twofold. It introduces a novel operator that applies symbolic linearization in a transparent and easy way to solve nonconvex OCPs with the SCQP method, and introduces a meaningful representation of an orientation-tunnel for robotic applications by means of a convex-over-nonlinear constraint, which preserves the convexity exploitation by the SCQP method. The proposed technique is demonstrated in a tunnel-following task for a 7-degrees-of-freedom manipulator.
Biportal Endoscopic Technique for Transforaminal Lumbar Interbody Fusion: Review of Current Research

Background There are many types of minimally invasive lumbar interbody fusion procedures. Among them is the recently introduced biportal endoscopic lumbar interbody fusion surgery. Biportal endoscopic transforaminal lumbar interbody fusion (TLIF) might combine the advantages of minimally invasive TLIF and endoscopic spine approaches. However, clinical evidence in support of biportal endoscopic TLIF remains insufficient. Methods A comprehensive review of English-language literature on biportal endoscopic lumbar interbody fusion was performed. Articles on biportal endoscopic TLIF in PubMed, the Cochrane Library, and Web of Science were searched using the terms “unilateral biportal endoscopy,” “biportal endoscopic spine surgery,” “transforaminal,” and “lumbar interbody fusion” as well as their combinations. The clinical and radiological outcomes of biportal endoscopic TLIF were analyzed and are summarized here. The biportal endoscopic lumbar interbody fusion surgical techniques are then described. Results There are 3 biportal endoscopic TLIF techniques. In the available literature, the postoperative 1-year outcomes of biportal endoscopic TLIF were comparable to those of posterior lumbar interbody fusion (PLIF) and minimally invasive (MIS)-TLIF. Clinical parameters were significantly improved after biportal endoscopic TLIF. Compared to PLIF or MIS-TLIF, biportal endoscopic-TLIF may have the advantage of a faster recovery. Biportal endoscopic TLIF showed no inferiority in fusion rates compared to PLIF or MIS-TLIF. The postoperative complications were usually minor. Conclusions The postoperative 1-year clinical and radiological outcomes of biportal endoscopic TLIF were favorable compared to those of PLIF and MIS-TLIF. However, long-term outcomes should be investigated through prospective, randomized controlled trials in the future. Clinical Relevance This review article outlines the most current evidence-based medicine with regard to spinal surgery with an aim to introduce a new technique.
Dynamic Reorganization of Functional Connectivity During Post-Break Task Reengagement

Because of the undesired fatigue-related consequences, accumulating efforts have been made to find an effective intervention to alleviate the suboptimal cognitive function caused by mental fatigue. Nonetheless, limitations of intervention and evaluation methods may hinder the revealing of underlying neural mechanisms of fatigue recovery. Through the newly-developed dynamic functional connectivity (FC) analysis framework, this study aims to investigate the effects of two types of mid-task interventions (i.e., rest-break and moderate-intensity exercise-break) on the dynamic reorganization of FC during the execution of psychomotor vigilance test (PVT). Using a sliding window approach, temporal brain networks within each frequency band (i.e., <inline-formula> <tex-math notation="LaTeX">$\delta $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\theta $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\alpha $ </tex-math></inline-formula>, & <inline-formula> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula>) were estimated before and immediately after the intervention, and towards the end of the task to investigate the immediate and delayed effects respectively during post-break task reengagement. Behaviourally, similar beneficial effects of exercise- and rest-break on performance were observed, manifested by the immediate improvements after both interventions and a long-lasting influence towards the end of tasks. Moreover, temporal brain networks assessment showed significant immediate decreases of fluctuability, which was followed by an increase of fluctuability towards the end of intervention tasks. Furthermore, the temporal nodal measure revealed the channels with significant differences across tasks were mainly resided in the fronto-parietal areas that exhibited interesting frequency-dependent distribution. The observations of immediate and delayed dynamic FC reorganizations extend previous fatigue-related intervention and static FC studies, and provide new insight into the dynamic characteristics of FC during post-break task reengagement.