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Background. Depression and anxiety frequently co-occur in chronic inflammatory diseases, with a prevalence of up to 20% in psoriatic arthritis. These patients may experience an increased risk of depression due to the influence of chronic pain and limitations in daily activities. In addition to the psychological effects of chronic illness, new research shows that systemic inflammation may directly cause anxiety and depression through neuroinflammatory pathways involving pro-inflammatory cytokines like TNF-alpha, IL-1beta, IL-6, IL-8, IL-17, and IL-23. The aim of the study is to evaluate the effect of b/ts-DMARDs therapies on anxiety-depressive symptoms and their relationship with disease activity.   Materials and Methods. We present a prospective single-center longitudinal study on a cohort of patients with psoriatic arthritis, rheumatoid arthritis, or axial spondyloarthritis starting b/ts-DMARDs therapy, either as first-line or subsequent treatment. Patients were assessed at baseline (T0) and at 3 months (T3) using HAQ, SF-36, SAS, and BDI, self-report questionnaires for functional disability, quality of life, and anxious and depressive symptoms. We will integrate the currently available data, which represent preliminary 3-month results, with ongoing follow-up. Statistical analyses included comparisons between T0 and T3, correlations between changes in psychometric scores and clinical and functional parameters, as well as analysis of the influence of sex, antidepressant use, and drug class administered.   Results. A total of 37 patients were included (mean age 54.9 ± 15.1 years; 75.7% women). At 3 months, patients experienced a mean worsening in BDI score (+3.22, SD 8.01) and SAS score (+1.94, SD 5.83), while their HAQ score improved (-0.24, SD 0.43). No significant differences were found in BDI, SAS, or HAQ score changes based on sex or antidepressant therapy. However, patients treated with antidepressants showed a mean reduction in SAS (-2.33) compared to an increase in untreated patients (+2.38), a clinically relevant but not statistically significant finding (p = 0.19). HAQ improved more in patients with lower disease activity (SDAI) (r = -0.55, p = 0.0127). Changes in BDI and HAQ were significantly associated with perceived emotional limitations in daily activities (SF-36 \"Role Emotional Limits,\" r = 0.49, p = 0.0049).   Conclusions. In the first 3 months of b/ts-DMARDs therapy, an improvement in functional disability is observed, but no benefit on anxiety-depressive symptoms, which in fact tend to worsen. This may reflect patients' disappointment with a clinical response perceived as incomplete, especially when chronic pain persists from sequelae, osteoarthritis, or fibromyalgia, often indistinguishable from inflammatory pain. It is therefore evident the importance of properly communicating realistic therapeutic goals to patients and integrating psychosocial support in the management of chronic inflammatory joint diseases.

Cancer cellular immunotherapy has made inspiring therapeutic effects in clinical practices, which brings new hope for the cure of cervical cancer. CD8+T cells are the effective cytotoxic effector cells against cancer in antitumor immunity, and T cells-based immunotherapy plays a crucial role in cellular immunotherapy. Tumor infiltrated Lymphocytes (TIL), the natural T cells, is approved for cervical cancer immunotherapy, and Engineered T cells therapy also has impressive progress. T cells with natural or engineered tumor antigen binding sites (CAR-T, TCR-T) are expanded in vitro , and re-infused back into the patients to eradicate tumor cells. This review summarizes the preclinical research and clinical applications of T cell-based immunotherapy for cervical cancer, and the challenges for cervical cancer immunotherapy.

As for many other organisms, CRISPR-Cas9 mediated genetic modification has gained increasing importance for the identification of vaccine candidates and drug targets in Neospora caninum , an apicomplexan parasite causing abortion in cattle and neuromuscular disease in dogs. A widely used approach for generating knock-out (KO) strains devoid of virulence factors is the integration of a drug selectable marker such as mutated dihydrofolate reductase-thymidylate synthase ( mdhfr-ts ) into the target gene, thus preventing the synthesis of respective protein and mediating resistance to pyrimethamine. However, CRISPR-Cas9 mutagenesis is not free of off-target effects, which can lead to integration of multiple mdhfr-ts copies into other sites of the genome. To determine the number of integrated mdhfr-ts in N. caninum , a duplex quantitative TaqMan PCR was developed. For this purpose, primers were designed that amplifies a 106 bp fragment from wild-type (WT) parasites corresponding to the single copy wtdhfrs-ts gene, as well as the mutated mdhfrs-ts present in KO parasites that confers resistance and were used simultaneously with primers amplifying the diagnostic NC5 gene. Thus, the dhfr-ts to NC5 ratio should be approximately 1 in WT parasites, while in KO parasites with a single integrated mdhrf-ts gene this ratio is doubled, and in case of multiple integration events even higher. This approach was applied to the Neospora KO strains Nc ΔGRA7 and Nc ΔROP40 . For Nc ΔGRA7 , the number of tachyzoites determined by dhfr-ts quantification was twice the number of tachyzoites determined by NC5 quantification, thus indicating that only one mdhfr-ts copy was integrated. The results obtained with the Nc ΔROP40 strain, however, showed that the number of dhfr-ts copies per genome was substantially higher, indicating that at least three copies of the selectable mdhfr-ts marker were integrated into the genomic DNA during gene editing by CRISPR-Cas9. This duplex TaqMan-qPCR provides a reliable and easy-to-use tool for assessing CRISPR-Cas9 mediated mutagenesis in WT N. caninum strains.

Analyses of mitochondrial cytochrome b diversity among avian blood parasites of the genera Haemoproteus and Plasmodium suggest that there might be as many lineages of parasites as there are species of birds. This is in sharp contrast to the approximately 175 parasite species described by traditional methods based on morphology using light microscopy. Until now it has not been clear to what extent parasite mitochondrial DNA lineage diversity reflects intra‐ or interspecific variation. We have sequenced part of a fast‐evolving nuclear gene, dihydrofolate reductase‐thymidylate synthase (DHFR‐TS), and demonstrate that most of the parasite mitochondrial DNA lineages are associated with unique gene copies at this locus. Although these parasite lineages sometimes coexist in the same host individual, they apparently do not recombine and could therefore be considered as functionally distinct evolutionary entities, with independent evolutionary potential. Studies examining parasite virulence and host immune systems must consider this remarkable diversity of avian malaria parasites.

Gas utilization ratio (GUR) is an important indicator that is used to evaluate the energy consumption of blast furnaces (BFs). Currently, the existing methods cannot predict the GUR accurately. In this paper, we present a novel data-driven model for predicting the GUR. The proposed approach utilized both the TS fuzzy neural network (TS-FNN) and the particle swarm algorithm (PSO) to predict the GUR. The particle swarm algorithm (PSO) is applied to optimize the parameters of the TS-FNN in order to decrease the error caused by the inaccurate initial parameter. This paper also applied the box graph (Box-plot) method to eliminate the abnormal value of the raw data during the data preprocessing. This method can deal with the data which does not obey the normal distribution which is caused by the complex industrial environments. The prediction results demonstrate that the optimization model based on PSO and the TS-FNN approach achieves higher prediction accuracy compared with the TS-FNN model and SVM model and the proposed approach can accurately predict the GUR of the blast furnace, providing an effective way for the on-line blast furnace distribution control.

Background Genomic imprinting (GI) is a mammalian‐specific epigenetic phenomenon that has been implicated in the evolution of the placenta in mammals. Methods Embryo transfer procedures and trophoblast stem (TS) cells were used to re‐examine mouse placenta‐specific GI genes. For the analysis of human GI genes, cytotrophoblast cells isolated from human placental tissues were used. Using human TS cells, the biological roles of human GI genes were examined. Main findings (1) Many previously identified mouse GI genes were likely to be falsely identified due to contaminating maternal cells. (2) Human placenta‐specific GI genes were comprehensively determined, highlighting incomplete erasure of germline DNA methylation in the human placenta. (3) Human TS cells retained normal GI patterns. (4) Complete hydatidiform mole‐derived TS cells were characterized by aberrant GI and enhanced trophoblastic proliferation. The maternally expressed imprinted gene p57KIP2 may be responsible for the enhanced proliferation. (5) The primate‐specific microRNA cluster on chromosome 19, which is a placenta‐specific GI gene, is essential for self‐renewal and differentiation of human TS cells. Conclusion Genomic imprinting plays diverse and important roles in human placentation. Experimental analyses using TS cells suggest that the GI maintenance is necessary for normal placental development in humans.

The originally identified transcription-defective fitA76 temperature-sensitive (Ts) mutation defined an allele of pheS. Both fitA/pheS and fitB/pheT were previously proposed to function as transcription factors. Sequencing pheS region of the fitA76 mutant revealed the same G293→A293 transition found in the translation-defective pheS5 mutant. It was subsequently found that fitA76 harbored a second mutation (fit95) in addition to pheS5 mutation. The fit95 was found to be Ts on –salt media but was found unstable. In this investigation, genetic, physiological and molecular characterization of the fit95 mutation was carried out. The fit95 was genetically re-separated from the pheS5 mutation present in the fitA76 mutant and the same was subsequently mobilized into multiple genetic backgrounds to study its phenotypic modulations by altering the medium and supplements. Based on genetic studies, the unstable –salt Ts phenotype of the fit95 could be stabilized by the presence of rpoB201 mutation. Addition of glucose enhanced Ts phenotype in the presence of rpoB201 mutation, but citrate completely alleviated the Ts phenotype. Further, by series of complementation analyses and molecular cloning, the identity of fit95 was revealed as pheT gene which is part of pheST operon.

Phasor measurement units (PMUs) are essential tools for monitoring, protection and control of power systems. The optimal PMU placement (OPP) problem refers to the determination of the minimal number of PMUs and their corresponding locations in order to achieve full network observability. This paper introduces a recursive Tabu search (RTS) method to solve the OPP problem. More specifically, the traditional Tabu search (TS) metaheuristic algorithm is executed multiple times, while in the initialisation of each TS the best solution found from all previous executions is used. The proposed RTS is found to be the best among three alternative TS initialisation schemes, in regard to the impact on the success rate of the algorithm. A numerical method is proposed for checking network observability, unlike most existing metaheuristic OPP methods, which are based on topological observability methods. The proposed RTS method is tested on the IEEE 14, 30, 57 and 118-bus test systems, on the New England 39-bus test system and on the 2383-bus power system. The obtained results are compared with other reported PMU placement methods. The simulation results show that the proposed RTS method finds the minimum number of PMUs, unlike earlier methods which may find either the same or even higher number of PMUs.

Background The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. Methods An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. Results There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). Conclusions Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.