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Anti-PD1/PDL1 therapy has proven efficacious against many cancers but only reached modest objective response rates against recurrent ovarian cancer. A deeper understanding of the tumor microenvironment (TME) may reveal other immunosuppressive mechanisms that warrant investigation as immunotherapeutic targets for this challenging disease. Matched primary and recurrent tumors from patients with high-grade serous ovarian carcinoma (HGSC) were analyzed by multicolor immunohistochemistry/immunofluorescence for the presence of T cells, B cells, macrophages, and for the expression of immunosuppressive and HLA molecules. Cancer- and immune-related gene expression was assessed by NanoString analysis. Recurrent tumors showed increased infiltration by immune cells, displayed higher expression of PDL1, IDO, and HLA molecules, and contained more stromal tissue. NanoString analysis demonstrated increased expression of gene signatures related to chemokines and T cell functions in recurrent tumors. The ovarian tumors showed high gene expression of LAG3 and HAVCR2 (TIM3) and enhanced levels of TIGIT and CTLA4 in recurrent tumors compared to primary tumors. The majority of HGSC developed into a more inflamed phenotype during progression from primary to recurrent disease, including indications of adaptive immune resistance. This suggests that recurrent tumors may be particularly sensitive to inhibition of adaptive immune resistance mechanisms.Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides-curdlan and hydroxypropyl cellulose. LDN-212854 Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250-300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach.Riveted workpieces are widely used in manufacturing; however, current inspection sensors are mainly limited in nondestructive testing and obtaining the high-accuracy dimension automatically is difficult. We developed a 3-D sensor for rivet inspection using fringe projection profilometry (FPP) with texture constraint. We used multi-intensity high dynamic range (HDR) FPP method to address the varying reflectance of the metal surface then utilized an additional constraint calculated from the fused HDR texture to compensate for the artifacts caused by phase mixture around the stepwise edge. By combining the 2-D contours and 3-D FPP data, rivets can be easily segmented, and the edge points can be further refined for diameter measurement. We tested the performance on a sample of riveted aluminum frame and evaluated the accuracy using standard objects. Experiments show that denser 3-D data of a riveted metal workpiece can be acquired with high accuracy. Compared with the traditional FPP method, the diameter measurement accuracy can be improved by 50%.This study investigated the geographic variation and the clustering of lung cancer incidence rates in Philadelphia and the surrounding areas using addresses at the time of diagnosis. Using 60,844 cases from Pennsylvania Cancer Registry, we calculated and mapped the age-adjusted incidence rates for five Pennsylvania (PA) counties near Philadelphia between 1998-2007 and 2008-2017. We identified ZIP codes with significantly higher incidence rates than the state rates and examined their demographic and exposure characteristics. Further, we tested for spatial autocorrelation and identified spatial clusters using Moran's I statistic. Our results showed that approximately one in four ZIP codes had an incidence rate that was significantly higher than the PA state rate in each period studied. Clusters of higher incidences were detected in the southeastern part of PA bordering New Jersey. These areas tended to be more populated, of lower socioeconomic status, and closer to manufacturing facilities and major highways. Possibly driven by the community and environmental factors, the observed differences in disease incidence suggest the importance of including residential location in risk assessment tools for lung cancer.Diabetes mellitus is a major factor contributing to the development of cardiovascular disease. As morbidity and mortality rates rise dramatically, when target organ damage develops pre-symptomatic assessment is critical for the management of diabetic patients. Echocardiography is a noninvasive and reproducible method that may aid in risk stratification and in evaluation of treatment effects. The aim of this review is to analyze the echocardiographic techniques which can detect early alteration in cardiac function in patients with diabetes.Dealing with health information and taking care of one's own health are key aspects of health literacy and a difficulty for nearly half of the population in Europe. Limited health literacy often results in poorer health outcomes. Health literacy is a fundamental health determinant, and its improvement provides great potential for addressing public health challenges. Health care organizations play an important role in improving population's health literacy. Health literate health care organizations facilitate access, understanding and use of health information and decrease the demands and complexities of the health care system. Few efforts have been taken so far to promote organizational health literacy, especially in German-speaking countries. This project aimed at developing a self-assessment tool, which enables primary care organizations to assess and improve their level of health literacy. The self-assessment tool was developed and evaluated with general practitioners and community care organizations in Switzerland. Here the participative development process, outcomes and the three modules of the self-assessment tool are presented (1) manual with detailed introduction and instruction, (2) checklist for self-assessment of organizational health literacy and (3) handbook with measures for improvement. The aim of this tool is that organizations are able to identify the need for action, plan and implement improvement measures.Pre-slaughter stunning is required for humane slaughter. For turkeys, head-only electrical stunning is most often used by small scale producers. To ensure immediate and effective stunning, the impedance (resistance) of the tissue of the head of the animal situated between the two electrodes needs to be overcome swiftly. The impedance is a function of the voltage and decreases non-linearly with increasing voltage. In this paper, we describe a method to assess the minimum voltage needed at which the impedance no longer decreases, that is likely to produce an effective stun. For ethical reasons, gas stunned, electrically naïve turkeys were used to measure impedance at various levels of voltage and current. Several combinations of voltage and frequency, alternate current (AC), direct current (DC) and pulsed DC, were identified that would be sufficient to achieve the maximum decrease in the impedance, and therefore would allow the highest current and the most effective stun. A minimum, expressed as Root Mean Squared voltage, of 150 V and 50 Hz. would be required in AC, 175 V in pulsed DC at 30% cycle (150 at 50% cycle), and 225 V if voltage spikes of very short duration were used. Sinusoidal AC applied at 150 V, 50 Hz was selected for further testing.South Asia continues to be the global hub for child undernutrition with 35% of children still stunted in 2017. This paper aimed to identify factors associated with stunting among children aged 0-23 months, 24-59 months, and 0-59 months in South Asia. A weighted sample of 564,518 children aged 0-59 months from the most recent Demographic and Health Surveys (2014-2018) was combined of five countries in South Asia. Multiple logistic regression analyses that adjusted for clustering and sampling weights were used to examine associated factors. The common factors associated with stunting in three age groups were mothers with no schooling ([adjusted odds ratio (AOR) for 0-23 months = 1.65; 95% CI (1.29, 2.13)]; [AOR for 24-59 months = AOR = 1.46; 95% CI (1.27, 1. 69)] and [AOR for 0-59 months = AOR = 1.59; 95% CI (1.34, 1. 88)]) and maternal short stature (height less then 150 cm) ([AOR for 0-23 months = 2.00; 95% CI (1.51, 2.65)]; [AOR for 24-59 months = 3.63; 95% CI (2.87, 4.60)] and [AOR for 0-59 months = 2.87; 95% CI (2.37, 3.48)]). Study findings suggest the need for a balanced and integrated nutrition strategy that incorporates nutrition-specific and nutrition-sensitive interventions with an increased focus on interventions for children aged 24-59 months.
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