Significant Response Research Articles

Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumorundergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome.

The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment(HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.

Immunoinformatic approaches for ErpY-LemA chimeric protein design for use in leptospirosis control.

Currently, immunoinformatic approaches have shown promise in rapidly and cost-effectively identifying new antigens from the Leptospira proteome. Chimeric multiepitope proteins offer a strategy with significant potential for implementation in serology and the design of effective vaccines. In this study, we detail the immunoinformatic analyses and design of a new recombinant chimeric protein constructed with epitopes identified from the sequences of ErpY-like and LemA proteins, previously identified as potential antigens for controlling leptospirosis. We expressed the chimeric protein using Escherichia coli heterologous systems, evaluated its antigenicity using serum from naturally infected patients, and its immunogenicity in mice as an animal model, with Freund as an adjuvant. The resulting recombinant chimeric protein, named rErpY-LemA, was successfully expressed and purified using a prokaryotic system, with an expected mass of 35 kDa. Serologic assays using serum samples from naturally infected patients demonstrated recognition of the chimera protein by antibodies present in sera. Animals immunized with the chimera exhibited a significant IgG antibody response from the 7th day (P<0.001), persisting until day 49 of experimentation, with a titer of 1:12,800 (P<0.05). Notably, significant production of IgA, IgM, and IgG subclasses was observed in animals immunized with the chimera. These results highlight the promising role of immunoinformatics in rapidly identifying antigens and the potential of chimeric multiepitope proteins in developing effective strategies for leptospirosis control.

Multiple Functional Protein-Protein Interaction Interfaces Allosterically Regulate ATP-Binding in Cyclin-Dependent Kinase-1.

The ATP-dependent phosphorylation activity of cyclin-dependent kinase 1 (CDK1), an essential enzyme for cell cycle progression, is regulated by interactions with Cyclin-B, substrate, and Cks proteins. We have recently shown that active site acetylation in CDK1 abrogated binding to Cyclin-B which posits an intriguing long-range communication between the catalytic site and the protein-protein interaction (PPI) interface. Now, we demonstrate a general allosteric link between the CDK1 active site and all three of its PPI interfaces through atomistic molecular dynamics (MD) simulations. Specifically, we examined ATP binding free energies to CDK1 in native nonacetylated (K33wt) and acetylated (K33Ac) forms as well as the acetyl-mimic K33Q and the acetyl-null K33R mutant forms, which are accessible in vitro. In agreement with experiments, ATP binding is stronger in K33wt relative to the other three perturbed states. Free energy decomposition reveals, in addition to expected local changes, significant and selective nonlocal entropic responses to ATP binding/perturbation of K33 from the -helix, activation loop (A-loop), and - H segments in CDK1 which interface with Cyclin-B, substrate, and Cks proteins, respectively. Statistical analysis reveals that while entropic responses of protein segments to active site perturbations are on average correlated with their dynamical changes, such correlations are lost in about 9%-48% of the dataset depending on the segment. Besides proving the bi-directional communication between the active site and the CDK1:Cyclin-B interface, our study uncovers a hitherto unknown mode of ATP binding regulation by multiple PPI interfaces in CDK1.

Immunogenicity and Protective Efficacy of a Single Intranasal Dose Vectored Vaccine Based on Sendai Virus (Moscow Strain) against SARS-CoV-2 Variant of Concern

The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed a vaccine construct, Sen-Sdelta(M), which expresses the full-length spike (S) protein of the SARS-CoV-2 delta variant. A single intranasal delivery of Sen-Sdelta(M) to Syrian hamsters and BALB/c mice induced high titers of virus-neutralizing antibodies specific to the SARS-CoV-2 delta variant. A significant T-cell response, as determined by IFN-γ ELISpot and ICS methods, was also demonstrated in the mouse model. Mice and hamsters vaccinated with Sen-Sdelta(M) were well protected against SARS-CoV-2 challenge. The viral load in the lungs and nasal turbinates, measured by RT-qPCR and TCID50 assay, decreased dramatically in vaccinated groups. The most prominent effect was revealed in a highly sensitive hamster model, where no tissue samples contained detectable levels of infectious SARS-CoV-2. These results indicate that Sen-Sdelta(M) is a promising candidate as a single-dose intranasal vaccine against SARS-CoV-2, including variants of concern.

Bronchodilator response in Post-COVID-19 patients undergoing pulmonary rehabilitation.

SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. In our study, we have examined 134 post-COVID patients (aged 54.83±14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. Prior to bronchial dilation, six out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score=-1.645) indicative of an obstructive airway disease. Following inhalation of a ß2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (&gt;200 mL ΔFEV1 and &gt;12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. Our data provides evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted ß2-inhalation therapy including subsequent reevaluation.

Real-Life Response to Biologics in Severe Asthma with Nasal Polyposis: Insights from the Belgian Severe Asthma Registry.

Nasal polyposis (NP) is a comorbidity of type 2 severe asthma (SA) which could influence response to SA biologics. We evaluated (super-) response in SA patients with (NP +) and without NP (NP-) enrolled in the Belgian Severe Asthma Registry (BSAR). 914 patients, of whom 31% NP + , were included. At enrollment, NP + patients had higher annual exacerbation rates, higher number of emergency room visits and more elevated type 2 biomarkers. In the longitudinal subanalysis of 104 patients, both groups had significant and similar asthma responses to asthma biologics, except for a greater increase in FEV1 in the NP + group. Super-response was achieved in 33 patients (32%), irrespective of NP status or type of biologic. In conclusion, both NP + and NP - patients had positive treatment responses, with some able to achieve super-response. In SA patients with NP, a greater FEV1 improvement as compared to SA patients without NP was observed.

Efficacy and safety of rechallenge [177Lu]Lu-PSMA-617 RLT after initial partial remission in patients with mCRPC: evaluation of a prospective registry (REALITY study).

Rechallenge of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [177Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT04833517) after they initially benefited from PSMA-RLT. Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [177Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [177Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE). After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed. [177Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT.

Visible-light responsive CdS-QDs modified InGaZnO synapse for biologically plausible color-to-gray conversion

The energy-efficient perceptual capabilities of the human visual system have inspired the development of optoelectronic neuromorphic devices to replicate the essential properties. Color vision that is highly important for perception and cognitive behaviors, such as object recognition, esthetics, and communication, has recently been reported based on optoelectronic neuromorphic devices. The responses to different wavelengths of light are mainly dependent on power density, whereas the eye recognizes color images based on luminosity. This Letter presents a quantum dots (QDs) modified InGaZnO (IGZO) synaptic transistor based on an IGZO/CdS-QDs/PMMA heterojunction. These IGZO-based synapses show significant responsivity to 655-nm light through the spectrum broadening by QDs. More importantly, luminance-based color-to-gray conversion can be realized with this device using a spike encoding scheme, transforming color images into grayscale in parallel. Notably, the QDs modified IGZO-based synapses demonstrated a remarkable 34.3% improvement in recognition accuracy on the multicolor MNIST dataset in comparison with the pristine devices. Our results indicate that this visible-light responsive IGZO-based synapse has great potential for endowing the neuromorphic visual system with enhanced color vision and provides a biologically plausible approach for color-to-gray conversion.

Mitigation of Parasitic and Drift Capacitance-Induced Nonlinear Current Responses for Stable and Sensitive Perovskite X-ray Detectors.

The development of perovskite direct X-ray detectors shows potential for advancing medical imaging and industrial inspection precision. To ensure the optimal energy conversion efficiency of X-rays for reducing radiation doses, it is necessary for perovskites with thicknesses reaching hundreds of micrometers or even several millimeters to be utilized. However, the nonlinear current response becomes uncertain with such high thicknesses. For instance, the prevailing theory regarding the rapid trapping and release of charges by shallow-level defects falls short in explaining the nonlinear current response observed in high-quality single-crystal samples. Moreover, a significant nonlinear current response can degrade the detection performance. Here, we elucidate peculiar parasitic and drift capacitance-induced nonlinear current responses in perovskites, which arise from bulk structural deficiencies and interface junction width variation in addition to shallow-level defects. Both theoretical analysis and experimental findings demonstrate the effective suppression of nonlinear current responses by establishing bulk heterojunctions and refining interface junctions. Consequently, we have successfully developed highly linear current-responsive detectors based on polycrystalline MAPbI3 thick films. Notably, these detectors achieve a record sensitivity of 2.3 × 104 μC·Gyair-1·cm-2 under 100 kVp X-ray irradiation with a low bias of 0.1 V/μm, enabling enduring and high-resolution X-ray imaging for high-density objects. Successful fabrication and testing of a 64 × 64-pixel flat-panel prototype detector affirm the widespread applicability of these strategies in rectifying nonlinear current responses in perovskite-based X-ray detectors.

Functional Characterisation of Surfactant Protein A as a Novel Prophylactic Means against Oncogenic HPV Infections

Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A’s suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A’s ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types.

Synthetic Alfalfa Infusion Odour Attracts Gravid Culex quinquefasciatus Under Laboratory Conditions.

Gravid culicine mosquitoes rely on olfactory cues for selecting breeding sites containing organic detritus. While this capacity of the mosquitoes is used for surveillance and control, the current methodology is unwieldy, unreliable and expensive in time and labour. This study evaluated the dose-dependent attraction and oviposition response of gravid Culex quinquefasciatus to alfalfa infusions. Through combined chemical and electrophysiological analyses, bioactive volatile organic compounds (VOCs) in the headspace of alfalfa infusions, eliciting attraction, were identified. While phenolic and indolic compounds were the most abundant bioactive VOCs, additional VOCs, including a monoterpene, were required to elicit a significant behavioural response to the synthetic odour blend of alfalfa infusions. Comparative analysis with the commercially available mosquito oviposition pheromone (MOP) was also conducted demonstrating that this standardised synthetic alfalfa infusion odour blend offers a promising lure for targeted surveillance and control of Culex mosquitoes, which may contribute to disease prevention and public health protection.

Insight into adsorption behaviors of shale oil in kerogen slit by molecular dynamics

Shale oil is predominantly stored in organic nanopores, with kerogen playing a pivotal role in its adsorption. This study utilizes molecular dynamics (MD) simulations to quantitatively investigate the adsorption behavior of multi-component shale oil within kerogen slits. Unlike previous studies that focused on single-component hydrocarbon fluids and simplified kerogen models to graphene, this research employs an authentic kerogen structure and a multi-component shale oil model, incorporating the effects of surface roughness. The research analyzes the interaction mechanisms and distribution patterns of light, medium, and heavy components within the pores. Additionally, it examines the effects of temperature, pore size, and wall surface physical and chemical properties on shale oil adsorption. Results indicate that strong adsorption between asphaltene and kerogen significantly reduces the width of the kerogen slits, inhibiting the adsorption of lighter components. The study introduces the concept of effective radius for kerogen slits and provides a quantitative analysis of the adsorption capacity of kerogen surfaces. Different kerogen surface roughness and chemical properties were compared to understand their influence on shale oil adsorption. Key findings show that with increasing temperature, the distribution of hydrocarbons becomes more uniform, with medium components showing the most significant response. Surface roughness of kerogen affects the adsorption capacity, although the component proportions remain consistent, while different chemical property surfaces influence selective adsorption and the overall adsorption amount of shale oil components. This research offers a deeper understanding of shale oil adsorption mechanisms and provides valuable insights for optimizing shale oil extraction and utilization.

Parkinson's Disease Progression and Exposure to Contaminated Water at Camp Lejeune.

We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression, but this has not been reported for VOCs. The objective of this study was to test whether PD progression is faster in individuals exposed to VOCs in water at Camp Lejeune. A cohort of 172,128 marines residing at Camp Lejeune between 1975 and 1985 was previously assembled. We identified individuals with PD in Veterans Health Administration and Medicare databases between 2000 and 2021. Using estimates derived by the US Agency for Toxic Substances and Disease Registry, we classified individuals as exposed or unexposed to VOCs in residential water. We used Kaplan-Meier and Cox regression models to test differences between exposed and unexposed groups in the time from PD diagnosis until psychosis, fracture, fall, or death. Among 270 persons with PD, 177 (65.6%) were exposed to VOCs in residential water. Median cumulative exposure was 4970 μg/L-months, >50-fold the permissible level. Time until psychosis, fracture, and fall were all shorter in the exposed group, with adjusted hazard ratios (HRs) exceeding 2: psychosis HR, 2.19 (95% confidence interval [CI]: 0.99-4.83); fracture HR, 2.44 (95% CI: 0.91-6.55); and fall HR, 2.64 (95% CI: 0.97-7.21). A significant dose response was observed for time to fall (P trend, 0.032). No differences were observed for time until death. PD progression may be faster in persons exposed to trichloroethylene and other VOCs in water decades earlier. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Multi-objective models for crop rotation planning problems

CONTEXTAgriculture is a vital component of the global economy and modern societies. It has undergone significant consolidation and transformation in response to the food supply crisis, highlighting the important relationship between humans and the environment. However, concerns remain about food security, particularly with the projected population growth of over 9.5 billion by 2050. The computerization of agri-food supply chains has emerged as a significant response to these challenges. OBJECTIVE(1) Develop a multi-objective model that explores both net return and crop diversity. (2) Solve the problem using techniques that guarantee optimality. (3) Evaluate the gain in crop diversity versus the net return of the optimized configuration. METHODSThe study presents four Multi-objective Mixed-Integer Linear Programming models with integer and binary decision variables for Crop Rotation Planning Problems. The objectives are to maximize net income and increase crop diversity and land utilization. RESULTS AND CONCLUSIONSThe study exclusively employs linear programming techniques to solve the models resulting in an optimal solution. A comparative analysis with existing models in the literature, which primarily focused on maximizing net income, yielded a noteworthy result. The proposed models demonstrate an average increase of 60% in crop diversity, with net return losses of less than 5%. SIGNIFICANCEIn conclusion, this research provides valuable information for crop rotation planning and highlights the importance of agricultural farm management and precision agriculture in addressing current challenges. The innovative nature of this research is exemplified by the use of mixed-integer linear programming techniques to solve a multi-objective problem with integer and binary variables. The obtained results demonstrate increased crop diversity and minimal economic losses, which have significant implications for several areas of agricultural science, policy, and practice.

Assessment of Novel Protein Ingredient Arthrospira platensis and Soybean Genotype Amino Acid and Oil Selection Improvements on Broiler Performance for a 28–42 d Feeding Period

Two experiments were conducted to assess the efficiency of including the novel protein ingredient Arthrospira platensis or improved soybean meal in a broiler diet. The first experiment aimed to determine the feeding value of soybean meal produced from varieties of soybeans bred for increased amino acid content (SBAA) and improved oil content (SBO) compared to a conventional soybean variety in an ANOVA design fed to Cobb 500 female broilers for 28–42 d. The SBAA and SBO soybeans contained overall higher amino acid content and lower oligosaccharide content compared to the conventional soybean variety in addition to improved oil quality. The second experiment assessed the novel protein ingredient microalgae, Arthrospira platensis (algae), and was conducted to evaluate algae and corn distillers’ grain (DDGS) inclusion on broiler performance for a 28–42 d feeding period in Cobb CF05 male broilers with a 2 × 2 factorial treatment array. Prior to the experimental period, all birds were reared on common feeds. In Experiment 1, birds were fed a diet containing 20% inclusion of an experimental soybean source in the form of full-fat soybean meal. In Experiment 2, the four dietary treatments consisted of diets containing algae at inclusion levels of either 0 or 2% and DDGS at inclusion levels of 0% and 8%. Diets were fed to 288 female broilers (Experiment 1) and 384 male broilers (Experiment 2), placed in eight replicate pens of twelve birds, and live performance was assessed from d 28 to 42. At d 42, six birds from each pen were randomly selected and processed for evaluation of carcass traits and incidence of woody breast. For Experiment 1, all performance data were analyzed using a one-way ANOVA using JMP Pro 16 software with diet as the fixed effect and block as a random effect. Statistical significance was considered at p ≤ 0.05. No significant responses were observed for any recorded measurement for live performance, carcass traits, or woody breast. All data in Experiment 2 were analyzed as a full factorial with a mixed model using JMP software with algae, DDGS, and algae × DDGS as fixed effects and block as a random effect. The F-protected Fisher’s LSD test was used to separate means when p ≤ 0.05. No significant responses were observed for the algae, DDGS, and algae × DDGS influences on BWG, FI, and FCR or processing characteristics; the ingredient source did not affect bird performance. Experimental soybean lines developed at the University of Arkansas were able to be incorporated into broiler diets without decreasing performance. Algae has the potential to be a protein-contributing ingredient for broilers.

Assessment of Novel Protein Ingredient Arthrospira platensis and Soybean Genotype Amino Acid and Oil Selection Improvements on Broiler Performance for a 28–42 d Feeding Period

Two experiments were conducted to assess the efficiency of including the novel protein ingredient Arthrospira platensis or improved soybean meal in a broiler diet. The first experiment aimed to determine the feeding value of soybean meal produced from varieties of soybeans bred for increased amino acid content (SBAA) and improved oil content (SBO) compared to a conventional soybean variety in an ANOVA design fed to Cobb 500 female broilers for 28–42 d. The SBAA and SBO soybeans contained overall higher amino acid content and lower oligosaccharide content compared to the conventional soybean variety in addition to improved oil quality. The second experiment assessed the novel protein ingredient microalgae, Arthrospira platensis (algae), and was conducted to evaluate algae and corn distillers’ grain (DDGS) inclusion on broiler performance for a 28–42 d feeding period in Cobb CF05 male broilers with a 2 × 2 factorial treatment array. Prior to the experimental period, all birds were reared on common feeds. In Experiment 1, birds were fed a diet containing 20% inclusion of an experimental soybean source in the form of full-fat soybean meal. In Experiment 2, the four dietary treatments consisted of diets containing algae at inclusion levels of either 0 or 2% and DDGS at inclusion levels of 0% and 8%. Diets were fed to 288 female broilers (Experiment 1) and 384 male broilers (Experiment 2), placed in eight replicate pens of twelve birds, and live performance was assessed from d 28 to 42. At d 42, six birds from each pen were randomly selected and processed for evaluation of carcass traits and incidence of woody breast. For Experiment 1, all performance data were analyzed using a one-way ANOVA using JMP Pro 16 software with diet as the fixed effect and block as a random effect. Statistical significance was considered at p ≤ 0.05. No significant responses were observed for any recorded measurement for live performance, carcass traits, or woody breast. All data in Experiment 2 were analyzed as a full factorial with a mixed model using JMP software with algae, DDGS, and algae × DDGS as fixed effects and block as a random effect. The F-protected Fisher’s LSD test was used to separate means when p ≤ 0.05. No significant responses were observed for the algae, DDGS, and algae × DDGS influences on BWG, FI, and FCR or processing characteristics; the ingredient source did not affect bird performance. Experimental soybean lines developed at the University of Arkansas were able to be incorporated into broiler diets without decreasing performance. Algae has the potential to be a protein-contributing ingredient for broilers.

Long-term humoral and cellular responses elicited by Gam-COVID-Vac vaccine in hemodialysis patients: A prospective cohort study

&lt;b&gt;Purpose: &lt;/b&gt;The aim of this study is to assess long-term immunogenicity of the recombinant adenoviruses 26 and 5 vector-based COVID-19 vaccine Gam-COVID-Vac (Sputnik V, developed by N. F. Gamaleya National Research Centre, Russia) in patients receiving maintenance hemodialysis (HD) compared to healthy subjects.&lt;br /&gt; &lt;b&gt;Materials &amp;amp; methods: &lt;/b&gt;A prospective cohort study included patients treated with maintenance HD (n=23) and healthy volunteers (n=28). The levels of anti-severe acute respiratory syndrome coronavirus-2 specific IgG as well as specific T-cell responses were quantified in all participants at two time points: one and six months after complete vaccination. All participates were adults, had been vaccinated twice with Gam-COVID-Vac and had no prior history of confirmed COVID-19.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;In both groups, IgG levels decreased from month one to six, however, antibodies did not decline more rapidly in HD group (analysis of variance p=0.7214 for the “time×group” interaction, non-adjusted model). At the end of the study, 48.0% of non-HD and 67.0% of HD participants showed T-cell positivity. T-spot counts dropped over time in non-HD controls, but not in HD subjects (p=0.0080 and p=0.1800, respectively).&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;Patients receiving HD maintain significant long-term humoral response after Gam-COVID-Vac vaccination, which is comparable to that in subjects with normal kidney function. Cellular response turned up to be more sustained over time in HD group.

Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs’ ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs’ efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

A disulfidptosis-related lncRNAs cluster to forecast the prognosis and immune landscapes of ovarian cancer

ObjectiveDisulfidptosis is a newly recognized form of regulated cell death that has been linked to cancer progression and prognosis. Despite this association, the prognostic significance, immunological characteristics and treatment response of disulfidptosis-related lncRNAs (DRLs) in ovarian cancer have not yet been elucidated.MethodsThe lncRNA data and clinical information for ovarian cancer and normal samples were obtained from the UCSC XENA. Differential expression analysis and Pearson analysis were utilized to identify core DRLs, followed by LASSO algorithm. Random Survival Forest was used to construct a prognostic model. The relationships between risk scores, RNA methylation, immune cell infiltration, mutation, responses to immunotherapy and drug sensitivity analysis were further examined. Additionally, qRT-PCR experiments were conducted to validate the expression of the core DRLs in human ovarian cancer cells and normal ovarian cells and the scRNA-seq data of the core DRLs were obtained from the GEO dataset, available in the TISCH database.ResultsA total of 8 core DRLs were obtained to construct a prognostic model for ovarian cancer, categorizing all patients into low-risk and high-risk groups using an optimal cutoff value. The AUC values for 1-year, 3-year and 5-year OS in the TCGA cohort were 0.785, 0.810 and 0.863 respectively, proving a strong predictive capability of the model. The model revealed the high-risk group patients exhibited lower overall survival rates, higher TIDE scores and lower TMB levels compared to the low-risk group. Variations in immune cell infiltration and responses to therapeutic drugs were observed between the high-risk and low-risk groups. Besides, our study verified the correlations between the DRLs and RNA methylation. Additionally, qRT-PCR experiments and single-cell RNA sequencing data analysis were conducted to confirm the significance of the core DRLs at both cellular and scRNA-seq levels.ConclusionWe constructed a reliable and novel prognostic model with a DRLs cluster for ovarian cancer, providing a foundation for further researches in the management of this disease.

Variable Effects of Experimental Sea-level Rise Conditions and Invasive Species on California Cordgrass

AbstractSea-level rise (SLR) will produce unprecedented changes in tidal marsh systems that already cope with daily tidal fluctuation, disturbances from storms, and salinity changes from droughts and runoff events. Additionally, negative impacts from non-native invasive species may alter marsh plants’ ability to respond to SLR stressors like increased inundation and salinity. Increasingly, tidal marsh communities must tolerate both changes in the physical environment from SLR and increased risk of invasion by non-native species. To assess the response of a threatened tidal marsh cordgrass (Spartina foliosa) to both stressors, we implemented a field experiment in San Francisco Bay, CA, USA, exposing cordgrass to a treatment that extended tidal inundation projected with SLR using a recently developed in situ method. At one of two field sites, we also enclosed the cordgrass with or without the invasive European green crab, Carcinus maenas. We found that cordgrass responded negatively to longer inundation, although these effects varied by site and year. In higher inundation treatments, cordgrass survival increased with increasing surface elevation of the plot. Cordgrass survival was lower in the presence of invasive green crabs relative to controls. We did not find interacting effects of responses to increased inundation and invasive species presence, which highlights the need to consider how latent or sequential effects of multiple stressors may affect ecosystems. This study demonstrates significant biological responses to invasive species presence and increased inundation. Evaluating relative effects and timing of multiple stressors, especially those induced by climate change and invasive species, will help us to manage threatened ecological communities in a changing world.