Investigating Immune Profiles in Differentiated Thyroid Cancer by Multiplex Immunofluorescence

BACKGROUND: As the most common endocrine malignancy in the United States (U.S.), differentiated thyroid cancer (DTC) accounts for 3.8% of all cancers in the U.S., with roughly 10% of cases progressing to distant metastatic DTC, which is associated with a poor five year survival outcome despite conventional management, including surgery and radioactive iodine ablation. Recently, novel immunotherapies have garnered attention as a viable therapeutic resource for patients with advanced DTC. However, the response to therapy has been variable and unpredictable, which may be associated with an immune suppressive circulating phenotype. Nonetheless, the intra-tumoral immune infiltrate remains to be elucidated, demonstrating a critical need to address the gap in understanding in order to better prognosticate the disease. OBJECTIVE: To identify and compare tumor-infiltrating immune markers with those present in the adjacent normal thyroid tissue, and collate these immune infiltrates with tumor characteristics. METHODS: Twenty-nine adult tissue samples containing tumor and stromal regions were collected from patients with DTC. The samples were analyzed using multiplex immunofluorescence (MxIF) with antibodies against cell-surface molecules CD56, PD-1, PD-L1, FOXP3, CD3, CD8, CD4, CD45, CD68, CD163, INOS, HLA-DR, CD33, and CD19. 17 of the specimens were analyzed using HALO and a positive threshold was assigned based on review by a trained researcher. RESULTS: In evaluating the immune profiles, important differences in the immune infiltrates between different stages of the cancer were observed. Generally, PD-1 and PD-L1 were highly expressed within the tumor, despite variability in lymphocyte infiltration, indicating the importance of PD-1 and PD-L1 as potential predictive biomarkers for the aggressiveness of thyroid cancer. Tumor from patients with distant metastases demonstrated higher T cell infiltration, T regulatory cells, macrophages and PD-L1 positive cells as compared to localized tumor. CONCLUSION: Immune profiling demonstrated significant differences between tumor and adjacent healthy regions, particularly in terms of PD-1 and PD-L1 expression and lymphocyte infiltration, indicating that higher intratumor infiltration of T regulatory cells, macrophages and PD-1/PD-L1 positive cells may be associated with advanced thyroid cancer. Therefore, the data demonstrates the efficacy of MxIF in gathering valuable information regarding the tumor microenvironment, which will have major implications in guiding the selection of patients for immunotherapy.https://digitalcommons.unmc.edu/surp2021/1042/thumbnail.jp

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A multi-objective evolutionary fuzzy system to obtain a broad and accurate set of solutions in intrusion detection systems

Intrusion detection systems are devoted to monitor a network with aims at finding and avoiding anomalous events. In particular, we focus on misuse detection systems, which are trained to identify several known types of attacks. These can be unauthorized accesses, or denial of service attacks, among others. Whenever it scans a trace of a suspicious event, it is programmed to trigger an alert and/or to block this dangerous access to the system. Depending on the security policies of the network, the administrator may seek different requirements that will have a strong dependency on the behavior of the intrusion detection system. For a given application, the cost of raising false alarms could be higher than carrying out a preventive access lock. In other scenarios, there could be a necessity of correctly identifying the exact type of cyber attack to proceed in a given way. In this paper, we propose a multi-objective evolutionary fuzzy system for the development of a system that can be trained using different metrics. By increasing the search space during the optimization of the model, more accurate solutions are expected to be obtained. Additionally, this scheme allows the final user to decide, among a broad set of solutions, which one is better suited for the current network characteristics. Our experimental results, using thewell-known KDDCup’99 problem, supports the quality of this novel approach in contrast to the state-of-the-art for evolutionary fuzzy systems in intrusion detection, as well as the C4.5 decision tre

Detection of schistosomiasis antibodies in urine patients as a promising diagnostic maker

AbstractObjectiveTo determine secreted antischistosoma antibodies in urine and to discern the epidemiological situation of schistosomiasis in the agricultural field labourers'camps city in the Gezira State-central Sudan.MethodsTotal of 66 urine and 66 serum paired samples were collected from those who confirmed parasitologically positive and negative with schistosomiasis from the two camps. Samples were tested using ELISA technique to measure and compare the immunoglobulin G (IgG) levels in serum and urine samples of schistosomiasis patients.ResultsThe overall prevalence of S. mansoni and S. haematobium was 53.8% and 15.4%, while the intensity were (2.04 GMEC) and (0.9 GMEC) respectively. The relative percentage of positive IgG individulas in urine was 92.40% where as 96.97% in serum. Statistically no significant difference between the IgG levels in serum and urine samples was observed.ConclusionsThis study shows that the detection of secreted IgG antibodies in urine can substitute serum for diagnosis of schistosomiasis

Sleep Quality Among People with Type 2 Diabetes Mellitus During COVID-19 Pandemic: Evidence from Qatar\u27s National Diabetes Center

Purpose: Sleep disturbance is suspected to increase during the COVID-19 pandemic, and people with type 2 DM are known to have a higher risk of sleep disturbance. We aimed to determine the prevalence and determinants of sleep disturbance through Pittsburgh Sleep Quality Index (PSQI) during the COVID-19 pandemic. Patients and methods: We randomly selected two hundred eighty-eight people with T2DM from the outpatient clinics of the National Diabetes Centre in Qatar. We used Chi-square, Mann-Whitney, Spearman, and Point Biserial correlation tests to examine the association between sleep quality and the independent variables. Finally, we conducted multiple logistics regression to identify the predictors of poor sleep quality and set the alpha level at 0.05. Results: In our sample, the mean age (±SD) was 51.4 (± 9.5) years, and 64.3% of the study participants were males. The median (IQR) duration of diabetes was 10 (11) years. Additionally, 6.3% of the participants were on insulin. The median HbA1c was 7.6% (2.4). Three in ten patients reported poor sleep quality (PSQI\u3e 5); (n=103; 35.8%). Poor sleep quality was statistically associated with young age, previous history of sleep disturbance, prior diagnosis of sleep disorders, high depression score, and high perceived stress score. After adjusting for confounders, only high depressive symptoms score and previous history of sleep disorder were significant predictors of poor sleep quality (p \u3c 0.001), with adjusted odd ratios of (aOR = 1.421; 95% CI: 1.242-1.625) and (aOR = 3.208; 95% CI: 1.574-6.537), respectively. Conclusion: The prevalence of poor sleep quality among people with T2DM during the COVID-19 pandemic is high. Physicians must screen for depression, stress, and previous history of sleep disorder to tackle poor sleep among T2DM

Additional file 1: of Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*. (DOC 124 kb

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I):a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial

Abstract Background Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. Methods The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18–50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. Discussion If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. Trial registration ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017