Predicting Hereditary Breast Cancer By Combining Family History And Medical Information

Breast cancer is a malignant tumor, commonly found in women but rarely in men. One in eight US women will have the chance of developing breast cancer in their lifetime. A family history analysis and genetic test can identify the potential carrier gene that cause hereditary breast cancer. Mutated genes such as BRCA1, BRCA2, Tp53 and PTEN confer high lifetime risk of breast cancers and are the most significant genes for clinical studies. The study goals of this thesis were to: 1) develop an open source software tool to predict the risk of hereditary breast cancer and mutation risk of breast cancer in any person, 2) predict the risk of hereditary breast cancer in the next generation by analyzing the inheritance patterns of the genes, and 3) exploit medical guidelines and connect it with information technology. In the program, we combine National Comprehensive Cancer Network (NCCN) guidelines of BRCA1/BRCA2, TP53, and PTEN gene mutations. We have sought the help of medical practitioners, medical literatures, and all other credential reports to validate the output of this research. The input data for this program are family history and other cancer risk assessment guidelines for the individual. We have developed this software tool in C++ and JavaScript. In the program, we identify a person’s family history, age, and gender through questionnaires and make an evaluation of different possibilities and outcome. We analyze the risk of mutation with the help of family history. We have considered first, second, and third-degree relatives and individuals who belong to Ashkenazi Jewish ancestry. After the analysis, and if the person is at risk, we predict the mutation risk of the next generation based on the gene’s inheritance pattern. This tool would help the members of the general public who have the least knowledge about breast cancer and genetic inheritance, and it would also help them to identify the presence of mutated genes

An Optimal Lysis Time Maximizes Bacteriophage Fitness in Quasi-Continuous Culture

Optimality models have a checkered history in evolutionary biology. While optimality models have been successful in providing valuable insight into the evolution of a wide variety of biological traits, a common objection is that optimality models are overly simplistic and ignore organismal genetics. We revisit evolutionary optimization in the context of a major bacteriophage life history trait, lysis time. Lysis time refers to the period spanning phage infection of a host cell and its lysis, whereupon phage progenies are released. Lysis time, therefore, directly determines phage fecundity assuming progeny assembly does not exhaust host resources prior to lysis. Noting that previous tests of lysis time optimality rely on batch culture, we implemented a quasi-continuous culture system to observe productivity of a panel of isogenic phage λ genotypes differing in lysis time. We report that under our experimental conditions, λ phage productivity is maximized around optimal lysis times ranging from 60 to 100 min, and λ wildtype strain falls within this range. It would appear that natural selection on phage λ lysis time uncovered a set of genetic solutions that optimized progeny production in its ecological milieu relative to alternative genotypes. We discuss this finding in light of recent results that lysis time variation is also minimized in the strains with lysis times closer to the λ wild-type strain

Climate, peace and security programming in the Arab States: Considerations for integrated programming in Jordan, Yemen, Iraq and Somalia

The link between climate change and peace and security is becoming increasingly evident as the world grapples with the consequences of a warming planet. Climate change exacerbates existing inequalities and conflicts, and acts as a catalyst for new ones, as competition for dwindling resources, such as water and land intensify. Rising sea levels and extreme weather events displace communities, straining host communities’ resources, leading to potential social unrest. Additionally, climate-induced food and water scarcity can speak conflict over access to these essential resources. Furthermore, climate change can amplify existing social and economic inequalities, which can contribute to instability and unrest. Understanding the climate, peace, and security linkages, and developing integrated policies and programmes across this nexus, is critical to ensuring global peace and security, and addressing humanitarian needs while supporting sustainable development. This brief - based on the outcomes of a stakeholder workshop held in Cairo in March 2023 - outlines several best practices and lessons learned for the design, implementation, and evaluation of integrated programming that builds resilience to both climate change and security risks

Single-Cell Approach Reveals Intercellular Heterogeneity in Phage-Producing Capacities

Bacteriophage burst size is the average number of phage virions released from infected bacterial cells, and its magnitude depends on the duration of an intracellular progeny accumulation phase. Burst size is often measured at the population level, not the single-cell level, and consequently, statistical moments are not commonly available. In this study, we estimated the bacteriophage lambda (ƛ) single-cell burst size mean and variance following different intracellular accumulation period durations by employing Escherichia coli lysogens bearing lysis-deficient ƛ prophages. Single lysogens can be isolated and chemically lysed at desired times following prophage induction to quantify progeny intracellular accumulation within individual cells. Our data showed that ƛ phage burst size initially increased exponentially with increased lysis time (i.e., period between induction and chemical lysis) and then saturated at longer lysis times. We also demonstrated that cell-to-cell variation, or “noise,” in lysis timing did not contribute significantly to burst size noise. The burst size noise remained constant with increasing mean burst size. The most likely explanation for the experimentally observed constant burst size noise was that cell-to-cell differences in burst size originated from intercellular heterogeneity in cellular capacities to produce phages. The mean burst size measured at different lysis times was positively correlated to cell volume, which may determine the cellular phage production capacity. However, experiments controlling for cell size indicated that there are other factors in addition to cell size that determine this cellular capacity

Protocol for Safe, Affordable, and Reproducible 1 Isolation and Quantitation 2 of SARS-CoV-2 RNA from Wastewater

The following protocol describes our workflow for processing wastewater with the goal of detecting the genetic signal of SARS-CoV-2. The steps include pasteurization, virus concentration, RNA extraction, and quantification by RT-qPCR. We include auxiliary steps that provide new users with tools and strategies that will help troubleshoot key steps in the process. This protocol is one of the safest, cheapest, and most reproducible approaches for the detection of SARS-CoV-2 RNA in wastewater. Furthermore, the RNA obtained using this protocol, minus the pasteurization step, can be sequenced both using a targeted approach sequencing specific regions or the whole genome. The protocol was adopted by the New York City Department of Environmental Protection in August 2020 to support their efforts in monitoring SARS-CoV-2 prevalence in wastewater in all five boroughs of the city. Owing to a pasteurization step, it is safe for use in a BSL1+ facility. This step also increases the genetic signal of the virus while making the protocol safe for the personnel involved. This protocol could be used to isolate a variety of other clinically relevant viruses from wastewater and serve as a foundation of a wastewater surveillance strategy for monitoring community spread of known and emerging viral pathogens

Toxicity Evaluation and Biocompatibility of Nanostructured Biomaterials

Biomaterials have occupied a prominent place in regenerative procedures to restore human health. Moreover, there is a greater need in understanding, analyzing and establishing their toxicity profile. These, when made into nano-sized constructions called nanostructured biomaterials, their regenerative potential is enhanced, which could influence their toxicity nature. This chapter intends to give comprehensive information on their nanotoxicology pathways at the cellular level, their entry pathways into the human body, and their potential consequences on human health. It clearly explains the cytocompatibility and biocompatibility of various nanostructured biomaterials for potential human health applications like drug delivery and tissue engineering. A detailed overview of various in vitro and in vivo evaluation methods of biocompatibility of nanomaterials are outlined in this chapter that researchers should address as they move forward in developing new systems for the field of regeneration

Detection of Mutations Associated with Variants of Concern Via High Throughput 2 Sequencing of SARS-CoV-2 Isolated from NYC Wastewater

Monitoring SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To date, most data on SARS-CoV-2 genetic diversity has come from the sequencing of clinical samples, but such studies may suffer limitations due to costs and throughput. Wastewater-based epidemiology may provide an alternative and complementary approach for monitoring communities for novel variants. Given that SARS-CoV-2 can infect the cells of the human gut and is found in high concentrations in feces, wastewater may be a valuable source of SARS-CoV-2 RNA, which can be deep sequenced to provide information on the circulating variants in a community. Here we describe a safe, affordable protocol for the sequencing of SARS CoV-2 RNA using high-throughput Illumina sequencing technology. Our targeted sequencing approach revealed the presence of mutations associated with several Variants of Concern at appreciable frequencies. Our work demonstrates that wastewater-based SARS-CoV-2 sequencing can inform surveillance efforts monitoring the community spread of SARS-CoV-2 Variants of Concern and detect the appearance of novel emerging variants more cheaply, safely, and efficiently than the sequencing of individual clinical samples

Two randomized trials of effect of live attenuated influenza vaccine on pneumococcal colonization

The human nasopharynx is frequently colonized by Streptococcus pneumoniae (the pneumococcus), serving as the reservoir for transmission, a state which necessarily precedes invasive pneumococcal infection. Influenza infection increases pneumococcal colonization density and dysregulates host immune responses, increasing the risk of secondary bacterial pneumonia and death

Tracking cryptic SARS-CoV-2 Lineages Detected in NYC Wastewater

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern. Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. Finally, pseudoviruses containing the spike amino acid sequence of these lineages were resistant to different classes of receptor binding domain neutralizing monoclonal antibodies. We offer several hypotheses for the anomalous presence of these lineages, including the possibility that these lineages are derived from unsampled human COVID-19 infections or that they indicate the presence of a non-human animal reservoir