Colon Cancer Tumor Location Defined by Gene Expression May Disagree With Anatomic Tumor Location

BackgroundCancers of the right colon have been shown to differ from left-side colon cancers in prognosis, response to epithelial growth factor receptor inhibitors, microsatellite instability and BRAF mutation status, and other molecular characteristics. Clinical application of these differences will benefit from a deeper understanding of how tumor location defines and is defined by gene expression.Materials and MethodsThis study was carried out using Affymetrix microarray datasets (Cohort A: training set, n = 352; validation set, n = 519) and samples from The Cancer Genome Atlas Colon Adenocarcinoma database (Cohort B: n = 408), in which tumor location was reported. Gene expression patterns characteristic of tumor side were identified in a manner unbiased by statistical classification method.ResultsIn the Cohort A validation set, the anatomic locations of 75% of tumors agree with the locations predicted by gene expression (so-called genomic location), whereas 8% of tumors had genomic locations discordant with their anatomic locations, and 17% of tumors had ambiguous genomic locations. Genomic location was a better predictor of microsatellite instability, CpG island methylator phenotype status, and BRAF mutation status than anatomic location. Tumors with ambiguous genomic location were significantly (P = 1.3 × 10⁻⁷) more likely to have the mesenchymal consensus molecular subtype (40%) than those with a specific genomic location (18%). A genomic signature to predict genomic location was defined.ConclusionTumor location is increasingly considered in deciding treatment of a colon tumor. We showed that genomic location was superior to anatomic location as a predictor of molecular characteristics, suggesting that it may be a more accurate predictor of response.     

A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications

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新型冠状病毒肺炎患者死亡影响因素分析

目的分析新型冠状病毒肺炎(COVID-19)患者死亡的影响因素,为临床上减少COVID-19患者的病亡率提供参考。方法回顾性分析本院2020年1月17日—2月25日期间所有COVID-19入院患者的病例资料,收集患者的性别、年龄、住院期间是否服用中药制剂、临床分型、合并症、核酸检测结果、入院时间、出院情况等相关指标进行统计分析。结果 COVID-19疫情期间,本院COVID-19患者的在院人数逐渐增多,最高峰期曾同时收治904名COVID-19患者。在2020年1月17日—2月25日期间本院共收治1305例COVID-19患者,其中男性632例,女性673例,男女比例1∶1.06。年龄分布在7～101岁,中位数为63(51,70)岁。不同性别之间,患者的年龄分布无明显差异。单因素分析结果显示患者的性别、年龄、治疗期间是否服用中药制剂、临床分型、是否合并基础疾病(高血压、冠心病、糖尿病、肿瘤及尿毒症)以及核酸检测结果均可影响患者的病亡率。Logistics多因素回归分析发现,服用中药制剂、临床分型以及是否合并基础疾病是COVID-19患者病亡的独立危险因素。结论 COVID-19患者死亡与多种因素有关,减少危重症的发生,控制基础疾病,稳定血压血糖,积极改善心脑血管条件及稳定肾功能等是提高COVID-19患者治疗效果的主要措施,并且早期应用中药治疗对减少COVID-19病亡率同样具有十分重要的作用。     

Biogenic silver,gold and copper nanoparticles - A sustainable green chemistry approach for cancer therapy

The advent of nanotechnology has revolutionized the way clinicians are treating cancers. Treatment for cancer includes surgery, radiotherapy, hormonal therapy, chemotherapy, and now nano therapy, which could be a possible alternative. This new treatment regime can be beneficial since it shows minimum side effects as compared to other treatment methods. Metallic nanoparticles synthesized through green chemistry by using biological entities minimizes the side effects and enhances the properties of the metal against cancer cells. These green nanoparticles are widely used in research and have shown promising cytotoxic activity against various cancer cell lines. Mechanistically, these nanoparticles can enter the cancer cell and cause cell death by the activation of various molecular pathways such as apoptosis, necrosis and autophagy. This review focuses on the metal nanoparticles (silver, gold and copper) synthesized by the green chemistry approach that have been utilized to study the cancer cell death and we are also discussing the underlying molecular pathways.     

The influence of environmental and health indicators on premature mortality: An empirical analysis of the City of Toronto's 140 neighborhoods

The objective of this paper was to assess the link between premature mortality and a combination of neighbourhood contextual (environmental and health) and compositional (socioeconomic and demographic) characteristics. We statistically and spatially examined six environmental variables (ultrafine particles, carcinogenic and non-carcinogenic pollutants, pollution released to air, tree cover, and walkability index), six health service indicators (number health providers, breast, colorectal and cervical cancer screening uptake rates, student nutrition program uptake rates, and healthy food index), and eight socioeconomic indicators (total income, Gini coefficient, two age categories – below and above 40 years, proportion of females to males, visible minorities, Indigenous peoples, education, less than grade 9) among 140 neighbourhoods of the City of Toronto in Ontario (Canada). We applied principal component analysis to identify patterns and to reduce the number of explanatory variables into combined component axes that represent unique variation in these confounded and overlapping factors. We then applied regression analysis to model the relationship between the indices of enviro-health and socioeconomics and their potential relationship with premature mortality. Residual spatial analysis was used to investigate any remaining spatial structure (such as neighbourhoods with higher residual premature mortality rates). Neighbourhood Equity Index was correlated with our enviro-health and socioeconomic indices. Premature mortality within neighbourhoods was predicted by poor cancer screenings, pollution, lack of tree canopy, increased uptake of student nutrition programs and high walkability index. A negative association between premature mortality and pollution was associated low walkability index and presence of visible minorities within neighbourhoods. There was some unexplained residual spatial variation in our model of premature mortality - especially along the shores of Lake Ontario and in neighbourhoods with major highways or road corridors: premature mortality in Toronto neighbourhoods was higher than expected along highway-corridor neighbourhoods and shorelines. Our analysis revealed a significant relationship between neighbourhood contextual features – both environmental and health – and premature mortality, suggesting that these contextual components of neighbourhoods can predict rates of urban premature mortality in Toronto.     

Dysregulated Brain Dynamics in a Triple-Network Saliency Model of Schizophrenia and Its Relation to Psychosis

Background

Schizophrenia is a highly disabling psychiatric disorder characterized by a range of positive “psychosis” symptoms. However, the neurobiology of psychosis and associated systems-level disruptions in the brain remain poorly understood. Here, we test an aberrant saliency model of psychosis, which posits that dysregulated dynamic cross-network interactions among the salience network (SN), central executive network, and default mode network contribute to positive symptoms in patients with schizophrenia.

Re-engineering the interpretation of electronic fetal monitoring to identify reversible risk for cerebral palsy: a case control series

Background: Even key opinion leaders now concede that electronic fetal monitoring (EFM) cannot reliably identify fetal acidemia which many vouch as the only labor mediated pathophysiologic precursor for cerebral palsy (CP). We have developed the “Fetal Reserve Index” – an algorithm combining five dynamic components of EFM (1. Rate, 2. Variability, 3. Accelerations, 4. Decelerations, and 5. Excessive uterine activity) considered individually that are combined with the presence of: 6. maternal, 7. obstetrical, and 8. fetal risk factors.

Objective: Here, we compare this 8-point fetal reserve index (FRI) against the performance of ACOG monograph criteria and ACOG Category systems for predicting risk for both CP and the need for emergency operative delivery (EOD). We then studied how varied management for screen positives (Red zone-defined below) impacts the outcome of such cases.

Study design: Four hundred twenty term patients were studied: all entered labor with normal EFMs and no apparent cause of harm except events of labor and delivery. Sixty subsequently developed CP, and 360 were apparently normal controls. An FRI, normal on all eight parameters scored 100%, 4 of the 8 was 50%, etc. We divided cases into Green zone >50%, Yellow 50–26%, and Red ≤25%. An FRI in the Red zone was considered a positive screen. We then compared performance metrics for the three evaluation schemes and differences between controls that reached Red against those controls whose worst scores were Green/Yellow.

Results: For detection of injury during labor, the FRI performed much better than the ACOG Category criteria (sensitivity 28%), and Category III (45%) (p?Conclusions: FRI shows better discrimination for adverse fetal outcome and EOD than traditional EFM interpretation. The Category system is a very poor, subjective screening method as the vast majority of CP babies never reach the “action point” result of Category III. While reaching the Red zone does not ordain a bad outcome, how it is managed, does. Compared to CP cases, Red controls were delivered faster, had higher FRIs, and often had prompt management including IR maneuvers, which improved the FRI and lowered the risk of EODs even for cases with normal outcomes. With further study and validation, the quantitative FRI approach may replace the current, very subjective interpretation with a quantitative “lab test” approach.     

Trends in advanced imaging and hospitalization for emergency department syncope care before and after ACEP clinical policy

ObjectivesTo describe recent trends in advanced imaging and hospitalization of emergency department (ED) syncope patients, both considered “low-value”, and examine trend changes before and after the publication of American College Emergency Physician (ACEP) syncope guidelines in 2007, compared to conditions that had no changes in guideline recommendations.MethodsWe analyzed 2002–2015 National Hospital Ambulatory Medical Care Survey data using an interrupted-time series with comparison series design. The primary outcomes were advanced imaging among ED visits with principal diagnosis of syncope and headache and hospitalization for ED visits with principal diagnosis of syncope, chest pain, dysrhythmia, and pneumonia. We adjusted annual imaging and hospitalization rates using survey-weighted multivariable logistic regression, controlling for demographic and visit characteristics. Using adjusted outcomes as datapoints, we compared linear trends and trend changes of annual imaging and hospitalization rates before and after 2007 with aggregate-level multivariable linear regression.ResultsFrom 2002 to 2007, advanced imaging rates for syncope increased from 27.2% to 42.1% but had no significant trend after 2007 (trend change: ?3.1%; 95%CI ?4.7, ?1.6). Hospitalization rates remained at approximately 37% from 2002 to 2007 but declined to 25.7% by 2015 (trend change: ?2.2%; 95%CI ?3.0, ?1.4). Similar trend changes occurred among control conditions versus syncope, including advanced imaging for headache (difference in trend change: ?0.6%; 95%CI ?2.8, 1.6) and hospitalizations for chest pain, dysrhythmia, and pneumonia (differences in trend changes: 0.1% [95%CI ?1.9, 2.0]; ?0.9% [95%CI ?3.1, 1.3]; and ?1.2% [95%CI ?5.3, 2.9], respectively).ConclusionsBefore and after the release of 2007 ACEP syncope guidelines, trends in advanced imaging and hospitalization for ED syncope visits had similar changes compared to control conditions. Changes in syncope care may, therefore, reflect broader practice shifts rather than a direct association with the 2007 ACEP guideline. Moreover, utilization of advanced imaging remains prevalent. To reduce low-value care, policymakers should augment society guidelines with additional policy changes such as reportable quality measures.