Identification of microbial DNA in human cancer

<p>Abstract</p> <p>Background</p> <p>Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered.</p> <p>Methods</p> <p>We have developed a genome-wide approach, called Digital Karyotyping Microbe Identification (DK-MICROBE), to identify genomic DNA of bacteria and viruses in human disease tissues. This method involves the generation of an experimental DNA tag library through Digital Karyotyping (DK) followed by analysis of the tag sequences for the presence of microbial DNA content using a compiled microbial DNA virtual tag library.</p> <p>Results</p> <p>To validate this technology and to identify pathogens that may be associated with human cancer pathogenesis, we used DK-MICROBE to determine the presence of microbial DNA in 58 human tumor samples, including brain, ovarian, and colorectal cancers. We detected DNA from Human herpesvirus 6 (HHV-6) in a DK library of a colorectal cancer liver metastasis and in normal tissue from the same patient.</p> <p>Conclusion</p> <p>DK-MICROBE can identify previously unknown infectious agents in human tumors, and is now available for further applications for the identification of pathogen DNA in human cancer and other diseases.</p

Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study

BACKGROUND: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Protein Microarrays for Cancer Diagnostics and Therapy

In this postgenomic age, cancer will be understood in intricate detail beyond the genomic level. New technologies are emerging that allow global proteomic level characterization, profiling and understanding. One of the most exciting emerging technologies of cancer proteomics is protein microarray. In this review, the different types of protein microarrays are discussed, including the methods, challenges and techniques of each type. Subsequently, the application of these specific methods to cancer diagnosis, prognosis and therapy will be overviewed, providing a general review of current methods, and proposing how protein arrays will help shape the future of oncoproteomics.</jats:p

Mutually orthogonal hamiltonian connected graphs

AbstractIn this work, we concentrate on those n-vertex graphs G with n≥4 and ē≤n−4. Let P1=〈u1,u2,…,un〉 and P2=〈v1,v2,…,vn〉 be any two hamiltonian paths of G. We say that P1 and P2 are orthogonal if u1=v1,un=vn, and uq≠vq for q∈{2,n−1}. We say that a set of hamiltonian paths {P1,P2,…,Ps} of G are mutually orthogonal if any two distinct paths in the set are orthogonal. We will prove that there are at least two orthogonal hamiltonian paths of G between any two different vertices. Furthermore, we classify the cases such that there are exactly two orthogonal hamiltonian paths of G between any two different vertices. Aside from these special cases, there are at least three mutually orthogonal hamiltonian paths of G between any two different vertices

FAULT-TOLERANT HAMILTONIAN LACEABILITY AND FAULT-TOLERANT CONDITIONAL HAMILTONIAN FOR BIPARTITE HYPERCUBE-LIKE NETWORKS

A bipartite graph G is hamiltonian laceable if there is a hamiltonian path between any two vertices of G from distinct vertex bipartite sets. A bipartite graph G is k-edge fault-tolerant hamiltonian laceable if G - F is hamiltonian laceable for every F ⊆ E(G) with |F| ≤ k. A graph G is k-edge fault-tolerant conditional hamiltonian if G - F is hamiltonian for every F ⊆ E(G) with |F| ≤ k and δ(G - F) ≥ 2. Let G0 = (V0, E0) and G1 = (V1, E1) be two disjoint graphs with |V0| = |V1|. Let Er = {(v,ɸ(v)) | v ϵ V0,ɸ(v) ϵ V1, and ɸ: V0 → V1 is a bijection}. Let G = G0 ⊕ G1 = (V0 ⋃ V1, E0 ⋃ E1 ⋃ Er). The set of n-dimensional hypercube-like graphHn is defined recursively as (a) H1 = K2, K2 is the complete graph with two vertices, and (b) if G0 and G1 are in Hn, then G = G0 ⊕ G1 is in Hn+1. Let Bn be the set of graphs G where G is bipartite and G ϵ Hn. In this paper, we show that every graph in Bn is (n - 2)-edge fault-tolerant hamiltonian laceable if n ≥ 2 and every graph in Bn is (2n - 5)-edge fault-tolerant conditional hamiltonian if n ≥ 3. </jats:p