Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach.

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few "classic" CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care.

Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach.

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically. In addition, natural killer cell-based, dendritic cell-based, and CAR T cell therapies have been also shown to be promising and effective immunotherapeutic approaches. In particular, CAR T cell therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing the generation of several modified CAR T cells with enhanced antitumor immunity. However, the emerging SARS-CoV-2 infection could hijack a patient's immune system by releasing pro-inflammatory interleukins and cytokines such as IL-1ß, IL-2, IL-6, and IL-10, and IFN-γ and TNF-α, respectively, which can further promote neutrophil extravasation and the vasodilation of blood vessels. Despite the significant development of advanced immunotherapeutic technologies, after a certain period of treatment, cancer relapses due to the development of resistance to immunotherapy. Resistance may be primary (where tumor cells do not respond to the treatment), or secondary or acquired immune resistance (where tumor cells develop resistance gradually to ICIs therapy). In this context, this review aims to address the existing immunotherapeutic technologies against cancer and the resistance mechanisms against immunotherapeutic drugs, and explain the impact of COVID-19 on cancer treatment. In addition, we will discuss what will be the future implementation of these strategies against cancer drug resistance. Finally, we will emphasize the practical steps to lay the groundwork for enlightened policy for intervention and resource allocation to care for cancer patients.

Vegetables.

Vegetables come in varied colors, forms, and tastes. Health specialists highly encourage inclusion of vegetables in one's diet due to their inherent nutritional worth. This chapter will cover selected vegetables from wide-ranging families like roots, stems, leafy greens, and cruciferous varieties. The broad choice of the designated vegetables is predicated on popular household preferences, nourishing value, and health benefits. These vegetables are also in common use and are obtainable at the market. The health features of the vegetables are covered in such a way that they provide the distinctive phytonutrient quality coupled with prominent health findings.

Fruits.

Fruits come in a wide variety of colors, shapes, and flavors. This chapter will cover selected fruits that are known to be healthy and highly nutritious. These fruits were chosen due to their common usage and availability. Since it is not possible to cover all health benefits or essential nutrients and important phytochemicals of the fruit composition, this chapter will focus on the key valuable constituents and their potential health effects.

Grains.

The grain group is small, hard, dry seeds, known to be more durable than other staple foods. They have been a part of the human diet for tens of thousands of years. The two foremost types of commercial grain crops are cereals and legumes or pulses, discussed in Chapter 13 "Seeds." A low intake of whole grains is actually the leading dietary risk factor for death and disease in the USA. Few healthy grains are discussed in this chapter that can help prevent health problems like heart diseases, diabetes, and cancers.

Nuts.

Nuts are fruits composed of two parts: an inedible hard shell and an edible seed. Nuts are known as an energy-dense and nutrient-rich food source. In general, nuts are recognized as a good source of fat, fiber, and protein. Nuts are extremely beneficial parts of any diet since their consumption may lower risk for some diseases, such as cardiovascular diseases and cancer. They are acknowledged for their low glycemic index owning to high unsaturated fat and protein content and relatively low carbohydrate content. They have been shown to increase cognitive function as well.

Seeds.

A wide variety of plant species provide edible seeds. Seeds are the dominant source of human calories and protein. The most important and popular seed food sources are cereals, followed by legumes and nuts. Their nutritional content of fiber, protein, and monounsaturated/polyunsaturated fats make them extremely nutritious. They are important additions to our daily food consumption. When consumed as part of a healthy diet, seeds can help reduce blood sugar, cholesterol, and blood pressure.