Explore the vast range of titles available.

Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.

Autoimmune rheumatoid arthritis (RA) is a systemic condition closely correlated with a variety of autoantibodies (Abs) that could be considered diagnostic and prognostic markers. The current research was designed to detect the diagnostic values for a number (n) of these auto-Abs in RA detection and to evaluate the accuracy of a combined diagnostic scheme. This prospective study was conducted between September 2021 and August 2022 and included 110 subjects with RA, 70 individuals with other autoimmune disorders as positive controls (PC), and 50 unrelated, apparently healthy individuals as healthy controls (HC). The eligibility criteria for all study groups were followed stringently. An enzyme-linked immunosorbent assay (ELISA) was employed to measure rheumatoid factors (RF), cyclic citrullinated peptide antibodies (CCP-Abs), mutated citrullinated vimentin antibodies (MCV-Abs), anti-perinuclear factor antibodies (APF-Abs), and anti-keratin antibodies (AKA). We calculated the specificity, sensitivity, and predictive values of all auto-Abs. Significantly higher levels of anti-CCP-Abs, anti-MCV-Abs, APF-Abs, and AKAs were reported in the RA patients compared to the HC and PC subjects. RF levels, however, were only statistically elevated when compared to the HC individuals. Anti-APF-Abs had a higher sensitivity rate (70.9%), and anti-CCP-Abs had a higher specificity rate (94.16%) compared to other auto-Abs, whereas the combined detection scheme revealed a higher sensitivity (81.81%) and excellent specificity (90.83%) compared to the two former auto-Abs. Anti-perinuclear factor-Ab was a highly sensitive test, and CCP-Ab was a surpassingly specific assay for identifying RA. Furthermore, the combined detection scheme is an essential serological approach for RA diagnosis and crucial in differentiating this disease from other autoimmune diseases, thus promoting early diagnosis and treatment.Autoimmune rheumatoid arthritis (RA) is a systemic condition closely correlated with a variety of autoantibodies (Abs) that could be considered diagnostic and prognostic markers. The current research was designed to detect the diagnostic values for a number (n) of these auto-Abs in RA detection and to evaluate the accuracy of a combined diagnostic scheme. This prospective study was conducted between September 2021 and August 2022 and included 110 subjects with RA, 70 individuals with other autoimmune disorders as positive controls (PC), and 50 unrelated, apparently healthy individuals as healthy controls (HC). The eligibility criteria for all study groups were followed stringently. An enzyme-linked immunosorbent assay (ELISA) was employed to measure rheumatoid factors (RF), cyclic citrullinated peptide antibodies (CCP-Abs), mutated citrullinated vimentin antibodies (MCV-Abs), anti-perinuclear factor antibodies (APF-Abs), and anti-keratin antibodies (AKA). We calculated the specificity, sensitivity, and predictive values of all auto-Abs. Significantly higher levels of anti-CCP-Abs, anti-MCV-Abs, APF-Abs, and AKAs were reported in the RA patients compared to the HC and PC subjects. RF levels, however, were only statistically elevated when compared to the HC individuals. Anti-APF-Abs had a higher sensitivity rate (70.9%), and anti-CCP-Abs had a higher specificity rate (94.16%) compared to other auto-Abs, whereas the combined detection scheme revealed a higher sensitivity (81.81%) and excellent specificity (90.83%) compared to the two former auto-Abs. Anti-perinuclear factor-Ab was a highly sensitive test, and CCP-Ab was a surpassingly specific assay for identifying RA. Furthermore, the combined detection scheme is an essential serological approach for RA diagnosis and crucial in differentiating this disease from other autoimmune diseases, thus promoting early diagnosis and treatment.

Adalimumab (Humira) represents a major advance in rheumatoid arthritis (RA) therapy. However, with long‐term administration of Adalimumab, anti‐idiotypic antibody (anti‐Id Ab) accelerates the Adalimumab clearance rate and reduces the therapeutic effect. To avoid the interference of anti‐Id Ab, we used an autologous hinge region as a spatial‐hindrance‐based Ab lock and connected it to the N‐terminal of the light chain and heavy chain via substrate peptides (MMP‐2/9) to cover the CDR binding site of Adalimumab to generate pro‐Adalimumab. The Ab lock masks the complementarity‐determining regions (CDRs) of Adalimumab, thus avoiding interference from anti‐Id Ab. Pro‐Adalimumab demonstrated a 241.6 times weaker binding ability to TNFɑ than Adalimumab. In addition, pro‐Adalimumab showed a 46.6‐fold greater blocking of anti‐Adalimumab Id Ab in comparison to Adalimumab prior to activation. Similar results were observed with other clinical antibodies, such as pro‐Infliximab (anti‐TNFɑ Ab) and pro‐Nivolumab (anti‐PD‐1). Furthermore, pro‐Adalimumab maintained consistent pharmacokinetics regardless of the presence of anti‐Adalimumab Id antibodies, while Adalimumab showed a 49% clearance increase, resulting in a near complete loss of function. Additionally, pro‐Adalimumab was able to avoid neutralization and efficiently reduce RA progression in the presence of anti‐Adalimumab Id Ab in vivo. In summary, we developed a pro‐Adalimumab that avoids interference from anti‐Id Abs, thereby addressing the biggest issue limiting clinical efficacy. The findings enclosed herein may have potentially broad application in antibody therapies.

Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint.

Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy.

Tumor-associated macrophages (TAMs) have been detected in most skin cancers. TAMs produce various chemokines and angiogenic factors that promote tumor development, along with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated neutrophils. TAMs generated from monocytes develop into functional, fully activated macrophages, and TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment. Since TAMs express PD1 to maintain the immunosuppressive M2 phenotype by PD1/PD-L1 signaling from tumor cells, and the blockade of PD1/PD-L1 signaling by anti-PD1 antibodies (Abs) activate and re-polarize TAMs into immunoreactive M1 phenotypes, TAMs represent a potential target for anti-PD1 Abs. The main population of TAMs comprises CD163+ M2 macrophages, and CD163+ TAMs release soluble (s)CD163 and several proinflammatory chemokines (CXCL5, CXCL10, CCL19, etc.) as a result of TAM activation to induce an immunosuppressive tumor microenvironment together with other immunosuppressive cells. Since direct blockade of PD1/PD-L1 signaling between tumor cells and tumor-infiltrating T cells (both effector T cells and Tregs) is mandatory for inducing an anti-immune response by anti-PD1 Abs, anti-PD1 Abs need to reach the tumor microenvironment to induce anti-immune responses in the tumor-bearing host. Taken together, TAM-related factors could offer a biomarker for anti-PD1 Ab-based immunotherapy. Understanding the crosstalk between TAMs and immunosuppressive cells is important for optimizing PD1 Ab-based immunotherapy.

Background: The aim of the rapid introduction of vaccines during the COVID-19 pandemic was a reduction in SARS-CoV-2 transmission and a less frequent occurrence of severe COVID-19 courses. Thus, we evaluated COVID-19 severity in vaccinated individuals to examine variant-specific symptom characteristics and their clinical impact on the serological immune response. Methods: A total of 185 individuals previously vaccinated against and infected with the SARS-CoV-2 Delta (B.1.617.2) or Omicron (BA.4 and BA.5) variant, were enrolled for anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig level detection. A structured survey regarding medical history was conducted. Results: In 99.5 percent of cases, outpatient treatment was satisfactory. Specific symptoms associated with variants included ageusia and anosmia in patients with Delta infections and throat pain in Omicron infections. Among Delta-infected individuals with specific symptoms, significantly higher levels of anti-N antibodies were observed. Conclusion: Our study identified variant-specific differences in the amount of SARS-CoV-2 antibody production and COVID-19 symptoms. Despite this, vaccinated individuals with Omicron or Delta infections generally experienced mild disease courses. Additionally, asymptomatic individuals exhibit lower anti-SARS-CoV-2 antibody levels, indicating a clinical correlation between disease-specific antibodies and distinct symptoms, particularly in the case of the Delta variant. In follow-up studies, exploring post-COVID syndrome and focusing on cognitive symptoms in the acute phase of Omicron infections is crucial as it has the potential to longitudinally impact the lives of those affected.

Introduction: Hepatitis B virus (HBV) infection remains a major health problem in Burkina Faso. To control and prevent HBV infection, Hepatitis B vaccine was introduced in the national expanded program in 2006. In this study, we evaluated the prevalence of HBsAg in children aged under 10 years after one decade of universal hepatitis B vaccination, and the immune response among these children. Methodology: Between May and October 2015, a cross-sectional study was conducted among children in two primary healthcare centers in the western region of Burkina Faso. Participants were enrolled in Accart-Ville Healthcare Center in Bobo-Dioulasso (urban area) and the Healthcare Center of the village of Djigouera (rural area). Blood samples were collected from all children and analysed for the presence of HBsAg and anti-HBs antibodies (Abs). For HBsAg positive children, blood samples were also taken among their mothers for screening for HBsAg. Results: A total of 265 children were included in this study. The mean age was 4.4 years. HBsAg was found in 3.4% (9/265) of children. Of the 9 HBsAg positive children, 5 had HBsAg positive mothers. From the 265 children tested for quantification of anti-HBs Ab titer, 219 (82.6%) were fully vaccinated and 135 (61.6%) of them had an anti-HBs ≥ 10 mIU/mL. Conclusion: Despite a good vaccination coverage (82.6%), a considerable proportion of vaccinated children remains unprotected from HBV infection. That emphasizes the need for further strengthening of the vaccination program through implementing the birth dose of HBV vaccine as recommended by WHO.

A vehicle with a four-channel anti-lock braking system (ABS) has poor safety and stability when braking on a low-adhesion road or off-road. In view of this situation, this paper proposes a multi-objective optimization coordinated control method for ABS and AFS based on multi-agent model predictive control (MPC). Firstly, the single-wheel control method is adopted to establish the single-wheel equation based on the slip rate and the stability equation of the centroid yaw based on AFS. The four wheels and the centroid are regarded as agents. The mathematical model of distributed drive electric vehicles based on graph theory and the coordinated control of AFS and ABS is established to reduce the dimension of the model. Secondly, on the basis of the multi-agent theory, an integrated coordinated control method for AFS and ABS based on distributed model predictive control (DMPC) is proposed to realize the ideal values of the vehicle’s slip rate, yaw rate, and sideslip angle, and improve the braking safety and handling stability of the vehicle. Then, to solve the problems of high levels of resource consumption, low real-time performance, and complex implementation in the optimization of the DMPC solution, a prediction solution method using a discrete simplified dual neural network (SDNN) is proposed to balance the computational efficiency and system dynamic performance. Finally, a hardware-in-the-loop (HIL) test bench is built to test the effectiveness of the proposed method under the conditions of a low-adhesion road and an off-road.

In track-oriented road cars with electric powertrains, the ability to recuperate energy during track driving is significantly affected by the frequent interventions of the antilock braking system (ABS), which usually severely limits the regenerative torque level because of functional safety considerations. In high-performance vehicles, when controlling an active rear wing to maximize brake regeneration, it is unclear whether it is preferable to maximize drag by positioning the wing into its stall position, to maximize downforce, or to impose an intermediate aerodynamic setup. To maximize energy recuperation during braking from high speeds, this paper presents a novel integrated open-loop strategy to control: (i) the orientation of an active rear wing; (ii) the front-to-total brake force distribution; and (iii) the blending between regenerative and friction braking. For the case study wing and vehicle setup, the results show that the optimal wing positions for maximum regeneration and maximum deceleration coincide for most of the vehicle operating envelope. In fact, the wing position that maximizes drag by causing stall brings up to 37% increased energy recuperation over a passive wing during a braking maneuver from 300 km/h to 50 km/h by preventing the ABS intervention, despite achieving higher deceleration and a 2% shorter stopping distance. Furthermore, the maximum drag position also reduces the longitudinal tire slip power losses, which, for example, results in a 0.4% recuperated energy increase when braking from 300 km/h to 50 km/h in high tire–road friction conditions at a deceleration close to the limit of the vehicle with passive aerodynamics, i.e., without ABS interventions.