Significant Advances In Detection Research Articles

From Detection to Protection: The Role of Optical Sensors, Robots, and Artificial Intelligence in Modern Plant Disease Management.

In the past decade, there has been a recognized need for innovative methods to monitor and manage plant diseases aiming to meet the precision demands of modern agriculture. Over the last 15 years, significant advances in detection, monitoring, and management of plant diseases have been made, largely propelled by cutting-edge technologies. Recent advances in precision agriculture have been driven by sophisticated tools such as sensors, artificial intelligence, microsensor networks, and autonomous vehicles. These technologies have enabled the development of novel cropping systems, allowing for targeted management of crops, contrasting with traditional, homogeneous treatment of large crop areas. Research in this field is usually highly collaborative, and interdisciplinary endeavor. It brings together experts from diverse fields such as plant pathology, computer science, statistics, engineering, and agronomy. Despite the progress, translating the advancements in the precision of decision-making or automation into agricultural practice remains a challenge. Enhancing the accuracy and timeliness of disease detection continues to be a priority, with data-driven artificial intelligence systems poised to play a pivotal role. This perspective addresses critical questions and challenges faced in the implementation of digital technologies for plant disease management. It underscores the urgency of integrating innovative technological advances with traditional integrated pest management (IPM). It highlights unresolved issues regarding the establishment of control thresholds for site-specific treatments and the necessary alignment of digital technology use with regulatory frameworks. Importantly, the paper calls for intensified research efforts, widespread knowledge dissemination, and education to optimize the application of digital tools for plant disease management.

Disparities in Time to Treatment for Breast Cancer: Existing Knowledge and Future Directions in the COVID-19 Era.

Despite significant advances in detection and treatment for breast cancer, the breast cancer mortality rate for Black women remains 40% higher than that for White women. Timely work-up and treatment improve outcomes, yet no gold standard exists for which to guide providers. A large body of literature demonstrates disparities in time to treatment for breast cancer, and most studies show that Black women receive treatment later than their White counterparts. The COVID-19 pandemic has been projected to worsen these disparities, but the extent of this impact remains unknown. In this review, we describe the available evidence on disparities in time to treatment, potential drivers, and possible mitigation strategies. Future research must address how the COVID-19 pandemic has impacted the timely treatment of breast cancer patients, particularly populations vulnerable to disparate outcomes. Improved access to multidisciplinary breast programs, patient navigation services, and establishment of standards for timely treatment are necessary.

A Novel MYH6E1503V Variant in a Family with a History of Heart Disease, including Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome (HLHS) is a severe form of congenital heart disease (CHD), requiring prompt surgical intervention and eventual transplant. Despite significant advances in detection and treatment of HLHS, genetic risk factors have been identified in <5% of patients. Our prior studies of 190 HLHS patients identified 19 distinct, rare variants in the gene encoding for a‐myosin heavy chain (MYH6), with variant carriers exhibiting reduced transplant‐free survival (p < 1 × 10−3). In‐depth genetic analysis was performed on the family of one HLHS subject who exhibited a novel E1503V variant in the tail domain of MYH6. The variant was identified in six additional members of the family, all of whom were related to the proband via the maternal grandmother. Four of those individuals also exhibited adult heart disease, with varying ages of onset. Though MYH6 variants have been implicated in a number of heart diseases – including arrhythmias, familial cardiomyopathies, as well as various forms of CHD – to our knowledge this is the first association of a single variant with both adult heart disease and HLHS.α‐myosin heavy chain (α‐MHC) is a cardiac‐specific protein that functions as a component of the sarcomere, the major contractile unit of the heart muscle. We therefore sought to evaluate functional consequences of MYH6E1503V on a‐MHC in vitro. Using CRISPR‐Cas9 gene editing technology, we successfully introduced the variant into induced pluripotent stem cells (iPSCs) from an unrelated individual, which were then used to generate cardiomyocytes. Subsequent evaluation of these cells revealed key insights into the effect of MYH6E1503V on sarcomere organization and contractile properties in cardiomyocytes, as well as their proliferation and differentiation capacity.Support or Funding InformationChildren's Research Institute at the Children's Hospital of Wisconsin, Little Hearts for Life Foundation, M.A is a member of the Medical Scientist Training Program at MCW, which is partially supported by a training grant from NIGMS T32‐GM080202This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Imaging gastrin-releasing peptide receptors (GRPRs) in prostate cancer

Despite significant advances in detection and treatment, prostate cancer (PC) remains the most common malignancy and a major cause of cancer death in men worldwide. Imaging is critically important for the diagnosis, staging, and management of men with prostate cancer (PC). The conventional imaging modalities have been employed for local and metastatic staging with limited performance. Whole-body positron emission tomography (PET) using prostate membrane antigen-based tracers is the most widely used in research and clinical applications in this scenario. However, other ways to image PC are available. Here, we review the clinical literatures on the use of gastrin-releasing peptide receptors (GRPRs) as targets for imaging patients with PC.

Abstract 1478: Anti-EMP2 IgG1 combined with anti-PD1/PDL1 antibodies synergistically reduce tumor load in animal models of breast cancer

Abstract Purpose: Despite significant advances in detection and medicine, the incidence and mortality due to breast cancer world-wide is still unacceptably high. Our recent work reveals that tetraspan protein epithelial membrane protein-2 (EMP2) is up-regulated in up to 70% of patients with invasive breast cancer and its expression is further augmented in metastatic lesions. New data suggests that EMP2 expression correlate with an increase in tumor associated PDL1 expression. We thus hypothesized that EMP2 expression regulated tumor immunogenicity through either direct control of PDL1 expression or MHC Class I processing. Recently, to determine the therapeutic potential of EMP2, our group created a panel of anti-EMP2 antibodies and new data shows that tumors treated with anti-EMP2 IgG1 show an increase in immune infiltrates. We thus proposed that EMP2 positive tumors will be amendable to anti-PD1/PDL1 therapy. Methods:A panel of breast cancer cell lines, both TNBC as well as hormone positive cell lines, were transfected with a vector to overexpress EMP2 or to reduce its levels. To determine if EMP2 expression influenced the expression of immune associated genes, RNAseq was performed. In addition, PDL1 protein expression was measured using standard immunohistochemistry or western blot analysis. Immune cell populations in various xenografts models were quantitated using standard immunohistochemistry. To determine the efficacy of combination anti-EMP2 and anti-PD1 therapy, syngeneic 4T1/firefly luciferase mouse models were created in BALB/c mice. Briefly, cells were injected into the mammary fat pad of female BALB/c mice, and once they approached 100 mm3, were injected IP with a)10 mg/kg dose twice a week of anti-EMP2 antibody, b) 5mg/kg twice a week with anti-PD-1 antibody (BioXCell), c) 10mg/kg ant-EMP2 and 5mg/kg of anti-PD-1 antibody twice a week, or d) saline control. Results: In multiple breast cell lines, EMP2 levels correlated with an increase in PDL1 expression, and treatment with anti-EMP2 IgG1 increased the number of infiltrating leukocytes. Using syngeneic mouse models, tumors treated with a combination of anti-EMP2 and anti-PD-1 antibodies grew slowly and had the smallest total volume compared to all other treatment groups. Anti-EMP2 IgG1 treatment was superior in reducing overall tumor volume compared to anti-PD-1 antibody treatment alone. Conclusions: Our preliminary data strongly supports the synergistic efficacy of anti-EMP2 IgG1 and anti-PD-1 antibody in reducing tumor load, suggesting that using anti-EMP2 treatment with an anti-PD1/PDL1 antibody may improve survival without inducing systemic toxicity as seen with chemotherapy. We predict that this is the direct result of EMP2 expression altering the immunogenicity of the tumor and in support of this, RNAseq data and western blot data suggest that EMP2 levels regulate PDL1 and MHC associated gene expression. Citation Format: Negin Ashki, Jessica Tsui, Madhuri Wadehra. Anti-EMP2 IgG1 combined with anti-PD1/PDL1 antibodies synergistically reduce tumor load in animal models of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1478.

P-0264 Carboxy-Terminal Telopeptide of Type I Collagene and Tartrate-Resistant Acid Posphatase Measurement in Patients with Colorectal Cancer and Bone Metastases

ABSTRACT Introduction Despite significant advances in detection and treatment, colorectal cancer (CRC) still remains one of the most prevalent cancers, and one of the leading causes of mortality due to malignancy. In patients with stage I-II CRC surgical resection usually represents the sole treatment, while in those with metastasized tumor (stage IV) any therapy is rarely successful. Unfortunately, up to 60% of patients with CRC undergoing primary surgery with curative intention die from metastatic disease. Thus, occult tumor cells, not detected preoperatively, likely colonize and remain vital in different tissues of these patients, such as lymph nodes, blood, and bone marrow. Usually, CRC metastasizes to the liver and lungs more frequently than to bone. Isolated bone metastasis (BM) is considered truly rare, but it has been observed that the improved survival for patients with metastatic CRC following expanded treatment options is associate with an increased incidence of BMs. Because metastases in uncommon sites often indicates the terminal phase of CRC, clinicians should be more vigilant about possible BMs. For this purpose, several serum biomarkers have been tested for early detection of BMs, such as carboxy-terminal telopeptide of type I collagen (ICTP), a cross-link product of collagen I degradation, and tartrate-resistant acid phosphatase 5b (TRACP), specifically derived from osteoclasts. Recent studies showed that TRACP activity and ICTP were increased in up to 90% of patients with breast cancer and BM. The aim of this study was to evaluate the usefulness of TRACP, ICTP, and bone alkaline phosphatase (BAP) measurements in patients with CRC and BM. Methods Fourteen patients (9 men, 5 women, mean age 56.1±4.8, range 49-63 years) with CRC and confirmed BMs (cases), and a group of 15 age- and gender matched (10 men, 4 women, age 57.1±4.9 years, p=0.08) patients (controls) without BM (negative F-18 FDG PET/CT) underwent serum TRACP, ICTP, and BAP measurements. Written informed consent was obtained from all the participants. TRACP and BAP were measured by two-site enzyme-linked immunosorbent assay (ELISA), while ICTP was measured by commercially available radioimmunoassay. The sensitivity and specificity of serum TRACP, ICTP, and BAP as a marker for BM were estimated by receiver operator characteristic (ROC) curves. Results The mean levels of TRACP, ICTP, and BAP (cases vs. controls) were: 5.9±1.6 vs. 4.8±1.3 U/L (95% CI 0.11-2.11, p=0.08), 6.9±1.4 vs. 5.9±1.3 U/L (95% CI 0.94-3.04, p=0.0003), and 82.6±18.2 vs. 79.3±16.2 (95% CI 9.81-16.39, p=0.59). ROC analysis established a cutoff value for ICTP of 4.51 U/mL to identify patients with extensive BM with a specificity of 97% and a sensitivity of 92% (area under the curve=0.97; 95% CI=0.95-0.98). A strong relationship was found only between TRACP and ICTP (R=0.95, p Conclusion Serum ICTP is a useful diagnostic marker in the detection of BMs in patients with CRC, more accurate than TRACP and BAP.

Abstract 3681: Helping Eve overcome ADAM: Characterization of the G-quadruplex in the ADAM15 core promoter

Abstract Breast cancer is the most common form of cancer in women, whose lethality is only surpassed by lung cancer. Through the last quarter-century there have been significant advances in detection and treatment options, such as Herceptin for HER2/neu positive cancers. While the development of targeted biological agents has greatly improved patient outcome, up to 70% of patients remain de novo refractory, relapse on therapy, or develop resistance. There is a pressing and eminent need for novel therapies to synergize with, or resensitize to, standard treatments. Enter ADAM15, with known zymogen, secretase, and disintegrin activies. This catalytically active member of the ADAM family is normally expressed in early embryonic development and is aberrantly expressed in various cancers, including breast. ADAM15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Seven independent microarray studies have shown that ADAM15 and HER2/neu are simultaneously upregulated in several stages of breast cancer, where their overexpression correlates with more aggressive and invasive disease. We have examined a unique string of GC-rich DNA within the critical core promoter of ADAM15. This region of DNA consists of seven tandem runs of three or more consecutive guanines. Under superhelical stress produced by the transcriptional complex, this region can relax from duplex DNA to form an intrastrand secondary structure known as a G-quadruplex. These globular entities generally serve as silencing elements for gene transcription. Furthermore, the topology of each G-quadruplex is as unique as a fingerprint. This allows for specific therapeutic targeting, offering a unique opportunity for treatment and selectivity over normal cells thus providing a potentially wide therapeutic window. Circular dichroism (CD) studies have confirmed the formation of a mixed parallel/anti-parallel G-quadruplex. Further CD analysis of the minimal G-quadruplex forming fragments has shown the capability of forming four unique thermally stable species. Electrophoretic mobility shift assay indicates the strongest intramolecular G-quadruplex formation in the 5′- and 3′-end runs of guanine, with minor intermolecular formations in the 3′-mid sequence, and a relatively unstable 5′-mid formation. To specifically determine which guanines are involved in the formation of the G-quadruplex and predict biologically relevant three-dimensional structures, DMS footprinting was performed on the full-length sequence and each of the four dissected regions. The pursuant data was used to build a molecular model of the structure. Full characterization of the G-quadruplex species formed will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3681.

Management of chronic hepatitis B in the liver transplant setting

Chronic viral hepatitis is the leading indication for orthotopic liver transplantation worldwide. Hepatitis B immunoglobulin and lamivudine (LAM) have been widely adopted as an effective treatment strategy against recurrent hepatitis B virus (HBV) infection in posttransplant patients. However, immunosuppression and the anti-hepatitis B surface (anti-HBs)–mediated immune pressure on HBV may culminate in the emergence and/or selection of immune escape HBV mutants. The emergence of mutations in the tyrosine methionine, aspartate, aspartate motif of the DNA polymerase represents a significant problem of long-term LAM therapy. Newer nucleoside analogs, such as adefovir dipivoxil (ADV) and entecavir, may provide a rescue therapy for LAM-resistant strains to avoid potential aggressive courses of HBV graft reinfection in liver transplant recipients. Previously, the selection of novel ADV-resistant mutations has been described in approximately 2% of patients over a 2-year treatment period. Five-year resistance surveillance programs are currently ongoing to monitor the emergence of ADV-resistant mutants in the long-term. Because of significant advances in detection, monitoring, and treatment options of hepatitis B, patient and graft survival have become excellent over the last years.

Development of prostate cancer treatment: the good news.

Prostate cancer is the most commonly diagnosed cancer in American men representing one-third of all new cancer cases each year. This translates into one out of every six American men being diagnosed with prostate cancer over the course of their lifetimes. Over 31,000 of these men die each year from prostate cancer. Before the 1980's, 50% of men were diagnosed with widespread metastatic disease and there were few therapeutic choices for patients. The good news for patients is that, over the last 30 years there have been significant advances in detection and prognostication as well as major improvements in the surgical, radiation, and medical oncological management of prostate cancer. This review describes the evolution of these therapeutic modalities for prostate cancer. This evolution has been driven by the explosion of knowledge concerning cancer in general and in the specific biology of prostate cancer in particular over the last 30 years. This knowledge has been obtained by concentrating human and financial resources in organ specific studies of the prostate. The end result of this effort is that, today, 85% of new prostate cancer cases are diagnosed at local and regional stages and the 5-year relative prostate cancer survival rate has increased by 20% since 1985. In addition, the therapeutic approach to prostate cancer can now be individualized based on the characteristics of the patient's disease. Finally, recent data suggest that the death rate from prostate cancer is decreasing by approximately 4% per year since 1994. Further good news for patients is that new discoveries about the biology of prostate cancer are rapidly being translated into new therapies, a large number of which are currently being tested in clinical trials. Continued allocation of appropriate human and material resources should yield new, more effective therapies for prostate cancer that will further impact patient quality of life and survival in the 21st century.