An Authentic-material-based Course Design on Resume Writing for EFL Students

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Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

MicroRNAs MiR-218, MiR-125b, and Let-7g Predict Prognosis in Patients with Oral Cavity Squamous Cell Carcinoma

<div><p>MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (<i>SP1</i>, <i>MYC</i>, and <i>TP53</i>) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.</p></div

Multivariable analysis of 5-year control and survival rates in OSCC patients (<i>n</i> = 58).

<p>Abbreviations: HR, hazard ratio; CI, confidence interval; ns, not significant.</p><p>* Indicates risk factors significantly associated with outcomes in univariate analysis.</p

Kaplan-Meier survival plots of OSCC patients according to traditional risk factors and miRNAs expression levels.

<p>(<b>A</b>) In the subgroup of patients with pT3-4 disease, subjects with high and low miR-125b expression had significantly different local control rates (92% vs. 50%); (<b>B</b>) the subgroup with low miR-218 expression showed a higher rate of distant metastases in patients with pN+ disease (86% vs. 57%); (<b>C</b>) a high let-7g expression was associated with a lower risk of tumor relapse in patients with advanced pathological stage (46% vs.71%); (<b>D</b>) an increased expression of let-7g predicted a better disease-specific survival in the subgroup of patients with pT3-4 disease (76% vs. 40%).</p

Prognostic miRNA modulators centered on the three hub genes <i>SP1</i>, <i>MYC</i>, and <i>TP53</i>.

<p>The downstream genes were grouped into outcome-specific clusters according to their prognostic significance (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102403#pone.0102403.s005" target="_blank">Tables S4</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102403#pone.0102403.s007" target="_blank">S6</a>). The associations between the upstream miRNAs and the downstream gene clusters were identified using sparse partial least square regression. Both the upstream miRNAs and the downstream responsive gene clusters showed a concordant prognostic impact on disease-free survival and disease-specific survival. The solid lines indicate the experimentally-confirmed physical interactions. The dotted lines show the results of the functional analysis performed using the DAVID package. <i>ABCA1</i>, <i>DDIT3</i>, <i>NDUFS8</i>, and <i>NDUFB9</i> regulate cell growth and proliferation. <i>TNFSF10</i> and <i>TNFRSF12A</i> are involved in the cell's apoptotic machinery. The remaining genes encode for molecules regulating cell adhesion or glycosaminoglycan metabolism. The miRNA modulators identified in this predicted poor outcomes in OSCC. Hopefully, our findings may lead to the development of novel prognostic models integrating molecular signatures and traditional risk factors for improving the prognostic stratification and the treatment modalities of OSCC patients.</p