Assessment of Early Growth Response 1 in Tumor Suppression of Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor survival despite surgical resection, and its pathogenesis has been broadly investigated in the past decade. Early growth response 1 (EGR-1) could involve regulating tumor development in ESCC cells. Methods: An attempt was made to examine the molecular and cellular influence of EGR-1 in esophageal cancer cells by RNA extraction, real-time PCR (qRT-PCR), cell culture, small interfering RNA (siRNA) knockdown, western blot, migration assay, and cell viability assay. One hundred and forty-four samples of ESCC were collected from our hospital and analyzed. Significantly higher EGR-1 expression was noted in tumor-adjacent normal tissue compared with tumor lesions. Results: The univariate analysis showed no significant impacts of EGR-1 expression on patients' survival. However, after adjusting for the pathological stage, patients with EGR-1 expression > 68th percentile had lower risks of cancer-related death. Moreover, knockdown of EGR-1 significantly enhanced cell migration, invasion, and resistance to chemotherapeutic agents in two ESCC cell lines. Conclusions: EGR-1 plays a key role in tumor suppression involving tumor viability suppression and reflects the treatment effect of current chemotherapy for ESCC.

Assessment of blinding in randomized controlled trials of antidepressants for depressive disorders 2000-2020: A systematic review and meta-analysis.

Background: In double-blind randomized controlled trials (RCTs) of antidepressants, blinding can be broken due to the apparent side effects, and unsuccessful blinding can lead to overestimation of effect sizes. New generation antidepressants with less severe side effects may be less susceptible to broken blinding. However, successfulness of blinding in new generation antidepressant trials and its influence on trial effect size estimates remain unclear. Methods: Extending a previous systematic review assessing blinding successfulness in psychiatric trials (2000-2010), we searched PubMed/Medline for double-blinded antidepressant RCTs (2010-2020) for trials assessing blinding success. Our primary outcome was the degree of blinding successfulness, measured as kappa statistics between guesses and true allocations. We used random-effects meta-analysis to synthesize studies. We used meta-regression and Pearson's r to examine the relationship between blinding success and effect sizes. This study is registered with PROSPERO (CRD42021249973). Findings: Among 154 eligible studies, 11 (7·1%) contained information on blinding assessment between 2010 and 2020. Five studies were added from the previous review, and altogether nine of the 16 studies provided usable data. Agreement in individual studies ranged from κ=-0·14 to 0·38. The summary agreement between guesses and the truth was 0·21 (95% CI: 0·14 to 0·28) among patients and 0·17 (95% CI: 0·05 to 0·30) among assessors. Blinding success was not associated with effect size (patients: r = 0·37, p = 0·32; assessors: r = 0·28; p = 0·72). Meta-regression also failed to find a significant relationship between blinding success and depression effect sizes (ß=0·06, p = 0·09). Interpretation: Less than 10% of the antidepressant RCTs reported blinding assessment. The results in new generation antidepressant trials indicated that patients and assessors were unlikely to be able to judge treatment allocation. There was little evidence that the extent of unblinding biased the effect size estimates of new generation antidepressants. Funding: None.

Exosome Processing and Characterization Approaches for Research and Technology Development.

Exosomes are extracellular vesicles that share components of their parent cells and are attractive in biotechnology and biomedical research as potential disease biomarkers as well as therapeutic agents. Crucial to realizing this potential is the ability to manufacture high-quality exosomes; however, unlike biologics such as proteins, exosomes lack standardized Good Manufacturing Practices for their processing and characterization. Furthermore, there is a lack of well-characterized reference exosome materials to aid in selection of methods for exosome isolation, purification, and analysis. This review informs exosome research and technology development by comparing exosome processing and characterization methods and recommending exosome workflows. This review also provides a detailed introduction to exosomes, including their physical and chemical properties, roles in normal biological processes and in disease progression, and summarizes some of the on-going clinical trials.

Decreased Incidence of Intraventricular Hemorrhage in Extremely Low Birth Weight Infants Using Customized Circulatory Management to Evaluate the Hemodynamic Change of Patent Ductus Arteriosus.

Background: In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants. Methods: We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia. Results: A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p = 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p = 0.017). Conclusion: The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective "early target therapy" for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.

A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation.

In view of recent intense experimental and theoretical interests in the biophysics of liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs), heteropolymer models with chain molecules configured as self-avoiding walks on the simple cubic lattice are constructed to study how phase behaviors depend on the sequence of monomers along the chains. To address pertinent general principles, we focus primarily on two fully charged 50-monomer sequences with significantly different charge patterns. Each monomer in our models occupies a single lattice site, and all monomers interact via a screened pairwise Coulomb potential. Phase diagrams are obtained by extensive Monte Carlo sampling performed at multiple temperatures on ensembles of 300 chains in boxes of sizes ranging from 52 × 52 × 52 to 246 × 246 × 246 to simulate a large number of different systems with the overall polymer volume fraction ϕ in each system varying from 0.001 to 0.1. Phase separation in the model systems is characterized by the emergence of a large cluster connected by intermonomer nearest-neighbor lattice contacts and by large fluctuations in local polymer density. The simulated critical temperatures, Tcr, of phase separation for the two sequences differ significantly, whereby the sequence with a more "blocky" charge pattern exhibits a substantially higher propensity to phase separate. The trend is consistent with our sequence-specific random-phase-approximation (RPA) polymer theory, but the variation of the simulated Tcr with a previously proposed "sequence charge decoration" pattern parameter is milder than that predicted by RPA. Ramifications of our findings for the development of analytical theory and simulation protocols of IDP LLPS are discussed.

Trend of urban-rural disparities in hospice utilization in Taiwan.

AIMS: The palliative care has spread rapidly worldwide in the recent two decades. The development of hospice services in rural areas usually lags behind that in urban areas. The aim of our study was to investigate whether the urban-rural disparity widens in a country with a hospital-based hospice system. METHODS: From the nationwide claims database within the National Health Insurance in Taiwan, admissions to hospices from 2000 to 2006 were identified. Hospices and patients in each year were analyzed according to geographic location and residence. RESULTS: A total of 26,292 cancer patients had been admitted to hospices. The proportion of rural patients to all patients increased with time from 17.8% in 2000 to 25.7% in 2006. Although the numbers of beds and the utilizations in both urban and rural hospices expanded rapidly, the increasing trend in rural areas was more marked than that in urban areas. However, still two-thirds (898/1,357) of rural patients were admitted to urban hospices in 2006. CONCLUSIONS: The gap of hospice utilizations between urban and rural areas in Taiwan did not widen with time. There was room for improvement in sufficient supply of rural hospices or efficient referral of rural patients.