Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

In-vitro antimicrobial effectiveness of herbal-based mouthrinses against oral microorganisms

Objective: To evaluate the in vitro antimicrobial effectiveness of commercial herbal-based mouthrinses against oral microorganisms. Methods: A total of three mouthrinses (OX, Pesona and Watsons) were tested for their antimicrobial activity against six oral organisms, Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Lactobacillus salivarius (L. salivarius), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Candida albicans (C. albicans) by standard agar-disk diffusion assay. Oradex mouthrinse containing 0.12% chlorhexidine gluconate and sterile distilled water was served as positive and negative controls, respectively. Results: All mouthrinse formulations were effective in inhibiting the growth of S. mutans, S. sobrinus, L. salivarius and C. albicans. Among the tested mouthrinses, Pesona was the only effective mouthrinse against S. aureus and P. aeruginosa, similar to Oradex mouthrinse. Pesona mouthrinse formulation appears to be as effective as Oradex mouthrinse formulation to kill S. aureus and P. aeruginosa. Statistical analysis showed no significant difference among the tested formulations regarding their antimicrobial activities (P > 0.05). Conclusions: Pesona was not the only herbal mouthrinse effective in inhibiting the growth of S. mutans, S. sobrinus, L. salivarius and C. albicans in vitro. All tested formulations were effective against those strains. Our findings may serve as a guide for selecting a kind of herbal mouthrinses as well as providing information to the dental professionals about the efficacy of these products

Differences in Characteristics, Hospital Care and Outcomes between Acute Critically Ill Emergency Department Patients with Early and Late Do-Not-Resuscitate Orders

Background: A do-not-resuscitate (DNR) order is associated with an increased risk of death among emergency department (ED) patients. Little is known about patient characteristics, hospital care, and outcomes associated with the timing of the DNR order. Aim: Determine patient characteristics, hospital care, survival, and resource utilization between patients with early DNR (EDNR: signed within 24 h of ED presentation) and late DNR orders. Design: Retrospective observational study. Setting/Participants: We enrolled consecutive, acute, critically ill patients admitted to the emergency intensive care unit (EICU) at Taipei Veterans General Hospital from 1 February 2018, to 31 January 2020. Results: Of the 1064 patients admitted to the EICU, 619 (58.2%) had EDNR and 445 (41.8%) LDNR. EDNR predictors were age &gt;85 years (adjusted odd ratios (AOR) 1.700, 1.027&ndash;2.814), living in long-term care facilities (AOR 1.880, 1.066&ndash;3.319), having advanced cardiovascular diseases (AOR 2.128, 1.039&ndash;4.358), &ldquo;medical staff would not be surprised if the patient died within 12 months&rdquo; (AOR 1.725, 1.193&ndash;2.496), and patients&rsquo; family requesting palliative care (AOR 2.420, 1.187&ndash;4.935). EDNR patients underwent lesser endotracheal tube (ET) intubation (15.6% vs. 39.9%, p &lt; 0.001) and had reduced epinephrine injection (19.9% vs. 30.3%, p = 0.009), ventilator support (16.7% vs. 37.9%, p &lt; 0.001), and narcotic use (51.1% vs. 62.6%, p = 0.012). EDNR patients had significantly lower 7-day (p &lt; 0.001), 30-day (p &lt; 0.001), and 90-day (p = 0.023) survival. Conclusions: EDNR patients underwent decreased ET intubation and had reduced epinephrine injection, ventilator support, and narcotic use during EOL as well as decreased length of hospital stay, hospital expenditure, and survival compared to LDNR patients

Emergency Department Referral for Hospice and Palliative Care Differs among Patients with Different End-of-Life Trajectories: A Retrospective Cohort Study

Emergency units have been gradually recognized as important settings for palliative care initiation, but require precise palliative care assessments. Patients with different illness trajectories are found to differ in palliative care referrals outside emergency unit settings. Understanding how illness trajectories associate with patient traits in the emergency department may aid assessment of palliative care needs. This study aims to investigate the timing and acceptance of palliative referral in the emergency department among patients with different end-of-life trajectories. Participants were classified into three end-of-life trajectories (terminal, frailty, organ failure). Timing of referral was determined by the interval between the date of referral and the date of death, and acceptance of palliative care was recorded among participants eligible for palliative care. Terminal patients had the highest acceptance of palliative care (61.4%), followed by those with organ failure (53.4%) and patients with frailty (50.1%) (p = 0.003). Terminal patients were more susceptible to late and very late referrals (47.4% and 27.1%, respectively) than those with frailty (34.0%, 21.2%) and with organ failure (30.1%, 18.8%) (p &lt; 0.001, p = 0.022). In summary, patients with different end-of-life trajectories display different palliative care referral and acceptance patterns. Acknowledgement of these characteristics may improve palliative care practice in the emergency department

ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells

Breast cancer resistance protein [BCRP/ATP-binding cassette subfamily G member 2 (ABCG2)] is a member of the ATP-binding cassette transporter family. The presence of ABCG2 on the plasma membrane in many kinds of human cancer cells contributes to multidrug resistance during chemotherapy, and it has been used as the side population marker for identifying cancer stem cells in lung cancers. We report here that, in addition to the membranous form, ABCG2 proteins are also found inside the nucleus, where they bind to the E-box of CDH1 (E-cadherin) promoter and regulate transcription of this gene. Increased expression of ABCG2 causes an increase of E-cadherin and attenuates cell migration, whereas knockdown of ABCG2 downregulates E-cadherin and enhances cell motility. In mice, xenografted A549 cells that have less ABCG2 are more likely to metastasize from the subcutaneous inoculation site to the internal organs. However, for the cancer cells that have already entered the blood circulation, an increased level of ABCG2, and correspondingly increased E-cadherin, may facilitate circulating cancer cells to colonize at a distant site and form a metastatic tumor. We propose a novel role for nuclear ABCG2 that functions as a transcription regulator and participates in modulation of cancer metastasis

Microfluidic systems for biosensing

In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful tool for biosensing, particularly in enriching and purifying molecules and cells in biological samples. Compared with conventional sensing techniques, distinctive advantages of using MFS for biomedicine include ultra-high sensitivity, higher throughput, in-situ monitoring and lower cost. This review aims to summarize the recent advancements in two major types of micro fluidic systems, continuous and discrete MFS, as well as their biomedical applications. The state-of-the-art of active and passive mechanisms of fluid manipulation for mixing, separation, purification and concentration will also be elaborated. Future trends of using MFS in detection at molecular or cellular level, especially in stem cell therapy, tissue engineering and regenerative medicine, are also prospected

Diversity of endocervical microbiota associated with genital Chlamydia trachomatis infection and infertility among women visiting obstetrics and gynecology clinics in Malaysia.

The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region

Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity

Background: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accelerate CRC pathogenesis/progression via regulating collpasin response mediator protein-2 (CRMP2). Accordingly, roles of CRMP2 in CRC and CRC-DM patients were investigated for elucidating the molecular convergence of CRC and DM. Methods: CRMP2 profile in tumor tissues from CRC and CRC-DM patients was investigated to explore the link between CRC and DM etiology. Meanwhile, molecular mechanism of glucose to regulate CRMP2 profile and CRC characteristics was examined in vitro and in vivo. Results: CRMP2 was significantly lower in tumor lesions and associated with advanced tumor stage in CRC-DM patients. Physiological hyperglycemia suppressed CRMP2 expression/activity and augmented malignant characteristics of CRC cells. Hyperglycemia promotes actin de-polymerization, cytoskeleton flexibility and cell proliferation/metastasis by downregulating CRMP2 profile and thus contributes to CRC disease progression. Conclusions: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Accordingly, altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies

Association between GRIN3A gene polymorphism in Kawasaki disease and coronary artery aneurysms in Taiwanese children.

Kawasaki disease (KD) is pediatric systemic vasculitis with the classic complication of coronary artery aneurysm (CAA). It is the leading cause of acquired cardiovascular diseases in children. Some severe cases present with multi-organ involvement or neurological dysfunction. To identify the role of the glutamate receptor, ionotropic, N-methyl-d-aspartate 3A (GRIN3A) in KD, we investigated genetic variations in GRIN3A in a Taiwanese cohort of 262 KD patients (76 with and 186 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between clinical characteristics and GRIN3A genetic variations in KD. According to univariate regression analysis, CAA formation in KD was significantly associated with fever duration (p < 0.0001), first Intravenous immunoglobulin (IVIG) used (days after day one of fever) (p < 0.0001), and the GRIN3A (rs7849782) genetic variant (p < 0.001). KD patients with GG+GC genotype showed a lower rate of developing CAA (GG+GC genotype: odds ratio = 0.26; 95% CI = 0.14-0.46). Significant associations were identified between KD with CAA complication and the GRIN3A (rs7849782) genetic variant by using multivariate regression analysis. Specifically, significant correlations were observed between KD with CAA complications and the presence of GG+GC genotypes for the GRIN3A rs7849782 single-nucleotide polymorphism (full model: odds ratio = 0.25; 95% CI = 0.14-0.46). Our results suggest that a polymorphism of the GRIN3A gene may play a role in KD pathogenesis