Corpus overview


MeSH Disease

Human Phenotype


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    Augmentation of anti-MDA5 antibody SERO implies severe disease MESHD in COVID-19 patients

    Authors: Changzheng Liu; Qian Wang; Yeming Wang; Geng Wang; Linghang Wang; Hong Chen; Tao Jiao; Chaojun Hu; Xiaobo Lei; Li Guo; Lili Ren; Mengtao Li; Xiaofeng Zeng; Dingyu Zhang; Bin Cao; Jianwei Wang

    doi:10.1101/2020.07.29.20164780 Date: 2020-08-01 Source: medRxiv

    Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV2) infection MESHD, which is associated with high mortality of coronavirus disease MESHD 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti- melanoma MESHD melanoma HP differentiation-associated gene 5 (MDA5) antibody SERO (Ab)-related dermatomyositis MESHD (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease MESHD (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody SERO is correlated with severe disease MESHD and unfavorable outcomes.

    Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection MESHD, and cancer therapy

    Authors: Sierra M. Barone; Alberta G.A. Paul; Lyndsey M. Muehling; Joanne A. Lannigan; William W. Kwok; Ronald B. Turner; Judith A. Woodfolk; Jonathan M. Irish

    doi:10.1101/2020.07.31.190454 Date: 2020-08-01 Source: bioRxiv

    For an emerging disease MESHD like COVID-19, systems immunology tools may quickly identify and quantitatively characterize cells associated with disease progression MESHD or clinical response. With repeated sampling, immune monitoring creates a real-time portrait of the cells reacting to a novel virus before disease MESHD specific knowledge and tools are established. However, single cell analysis tools can struggle to reveal rare cells that are under 0.1% of the population. Here, the machine learning workflow Tracking Responders Expanding (T-REX) was created to identify changes in both very rare and common cells in diverse human immune monitoring settings. T-REX identified cells that were highly similar in phenotype and localized to hotspots of significant change during rhinovirus and SARS-CoV-2 infections MESHD. MHC tetramers were not used during unsupervised analysis and instead left out to serve as a test of whether T-REX identifies biologically significant cells. In the rhinovirus challenge study, T-REX identified virus-specific CD4+ T cells based on these cells being a distinct phenotype that expanded by [≥]95% following infection MESHD. T-REX successfully identified hotspots with virus-specific T cells using pairs of samples comparing Day 7 of infection MESHD to samples taken either after clearing the infection MESHD (Day 28) or samples taken prior to infection MESHD (Day 0). Mapping pairwise comparisons in samples according to both the direction and degree of change provided a framework to compare systems level immune changes during infectious disease MESHD or therapy response. This revealed that the magnitude and direction of systemic immune change in some COVID-19 patients was comparable to that of blast crisis MESHD acute myeloid leukemia MESHD acute myeloid leukemia HP patients undergoing induction chemotherapy and characterized the identity of the immune cells that changed the most. Other COVID-19 patients instead matched an immune trajectory like that of individuals with rhinovirus infection MESHD or melanoma MESHD melanoma HP patients receiving checkpoint inhibitor therapy. T-REX analysis of paired blood SERO samples provides an approach to rapidly identify and characterize mechanistically significant cells and to place emerging diseases MESHD into a systems immunology context.

    Prognostic Significance of COVID-19 Receptor ACE2 and Recommendation For Anti-Hypertensive Drug in Renal Cell Carcinoma MESHD Renal Cell Carcinoma HP

    Authors: Kihun Kim; Yeji Ko; Dai Sik Ko; Yun Hak Kim

    doi:10.21203/ Date: 2020-07-27 Source: ResearchSquare

    Background: Owing to its worldwide spread, the coronavirus disease MESHD (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys, and plays an important role in molecular docking of the severe acute respiratory syndrome MESHD coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. Methods: The clinical and genomic data of pan-cancer patients were accessed from The cancer Genome Atlas. To identify the prognostic significance of ACE2, we used Kaplan-Meier with log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. Results: In the Kaplan-Meier curve, clear cell renal cell carcinoma HP renal cell carcinoma MESHD (ccRCC), uveal melanoma HP melanoma MESHD, and prostate adenocarcinoma MESHD showed statistically significant. In the Cox regression, thyroid carcinoma HP carcinoma MESHD and glioblastoma MESHD glioblastoma multiforme HP multiforme, and ccRCC showed significant results. Only ccRCC had statistically significant, and high ACE2 expression is related to good prognosis. Conclusions: It is known that ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.

    Unemployment and health-related quality of life in melanoma MESHD melanoma HP patients during the COVID-19 pandemic: A web-based cross-sectional study

    Authors: Yeye Guo; Minxue Shen; Xu Zhang; Yi Xiao; Shuang Zhao; Mingzhu Yin; Wenbo Bu; Yan Wang; Xiang Chen; Juan Su

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    Background The outbreak of coronavirus disease MESHD-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma MESHD melanoma HP during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma MESHD melanoma HP.Methods A self-administered online questionnaire was distributed to melanoma MESHD melanoma HP patients through social media. Demographic and clinical data, and pandemic-related impacts (unemployment and income loss) were collected. HRQoL was determined by the Functional Assessment of Cancer Therapy-General (FACT-G) and its disease MESHD-specific module (the melanoma MESHD melanoma HP subscale, MS).Results A total of 70 patients with melanoma MESHD melanoma HP completed the study. The mean age TRANS of the patients was 55.2 ± 14.8 years, 45.7% (32/70) were male TRANS, and 21.4% (15/70) were unemployed since the epidemic. Unemployment of the patients and their family members TRANS and income loss were significantly associated with a lower FACT-G score, while the MS score was associated with the unemployment of the patients’ family members TRANS.Conclusions Our findings suggested that unemployment is associated with impaired HRQoL in melanoma MESHD melanoma HP patients during the COVID-19 epidemic.

    An inverse stage-shift model to estimate the excess mortality and health economic impact of delayed access to cancer services due to the COVID-19 pandemic

    Authors: Koen Degeling; Nancy N Baxter; Jon Emery; Fanny Franchini; Peter Gibbs; G Bruce Mann; Grant McArthur; Benjamin J Solomon; Maarten J IJzerman

    doi:10.1101/2020.05.30.20117630 Date: 2020-05-30 Source: medRxiv

    Background: Decreased cancer incidence and reported changes to clinical management indicate that the COVID-19 pandemic will result in diagnostic and treatment delays for cancer patients. We aimed to develop a flexible model to estimate the impact of delayed diagnosis and treatment initiation on survival outcomes and healthcare costs based on a shift in the disease MESHD stage at treatment initiation. Methods: The stage-shift model estimates population-level health economic outcomes by weighting disease MESHD stage-specific outcomes by the distribution of stages at treatment initiation, assuming delays lead to stage-progression. It allows for extrapolation of population-level survival data using parametric distributions to calculate the expected survival in life years. The model was demonstrated based on an analysis of the impact of 3 and 6-month delays for stage I breast cancer, colorectal cancer and lung cancer patients, and for T1 melanoma MESHD melanoma HP, based on Australian data. In the absence of patient-level data about time to stage progression, two approaches were explored to estimate the proportion of patients that would experience a stage shift following the delay: 1) based on the relation between time to treatment initiation and overall survival (breast, colorectal and lung cancer), and 2) based on the tumour growth rate ( melanoma MESHD melanoma HP). The model is available on Results: A shift from stage I to stage II due to a 6-month delay is least likely for colorectal cancer patients, with an estimated proportion of 3% of the stage I patients diagnosed in 2020 progressing to stage II, resulting in 11 excess deaths MESHD after 5 years and a total of 96 life years lost over a 10-year time horizon. For breast and lung cancer, progression from stage I to stage II due to a 6-month delay were slightly higher at 5% (breast cancer) and 8% (lung cancer), resulting in 25 and 43 excess deaths MESHD after 5 years, and 239 and 373 life years lost over a 10-year time horizon, respectively. For melanoma MESHD melanoma HP, with 32% of T1 patients progressing to T2 disease MESHD following a 6-month delay, the model estimated 270 excess death MESHD after 5 years and 2584 life years lost over a 10-year time horizon. Conclusions: Using a conservative 3-month delay in diagnosis and treatment initiation due to the COVID-19 pandemic, this study predicts nearly 90 excess deaths MESHD and $12 million excess healthcare costs in Australia over 5 years for the in 2020 diagnosed patients for 4 cancers. If the delays increase to 6 months, excess mortality and cost approach nearly 350 deaths MESHD and $46 million in Australia. More accurate data on stage of disease MESHD during and after the COVID-19 pandemic are critical to obtain more reliable estimates.

    Cancer immunotherapy does not increase the risk of death MESHD by COVID-19 in melanoma MESHD melanoma HP patients

    Authors: Maria Gonzalez-Cao; Monica Antonazas-Basa; Teresa Puertolas; Eva Munoz-Couselo; Jose Luis Manzano; Cristina Carrera; Ivan Marquez-Rodas; Pilar Lopez-Criado; Juan Francisco Rodriguez-Moreno; Almudena Garcia-Castano; Juan Martin-Liberal; Pedro Rodriguez-Jimenez; Susana Puig; Pablo Cerezuela; Marta Feito-Rodriguez; Belen Rubio-Viqueira; Guillermo Crespo; Pablo Luna-Fra; Cristina Aguayo; Pablo Ayala de Miguel; Rosa Feltes; Lara Valles; Ana Drozdowskyj; Ainara Soria; Cayetana Maldonado; Luis Fernandez-Morales; Rafael Rosell; Mariano Provencio; Alfonso Berrocal

    doi:10.1101/2020.05.19.20106971 Date: 2020-05-21 Source: medRxiv

    Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection MESHD in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection MESHD in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies SERO. There are no clinical data about the safety of immune check point antibodies SERO in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies SERO, are an effective treatment for most melanoma MESHD melanoma HP patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma MESHD melanoma HP. Methods: In Spain we have started a national registry of melanoma MESHD melanoma HP patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma MESHD melanoma HP patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age TRANS is 69 years (range 6 to 94 years), 27 (54%) patients are males TRANS and 36 (70%) patients have stage IV melanoma MESHD melanoma HP. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies SERO, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma MESHD melanoma HP progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma MESHD melanoma HP treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death MESHD in those patients undergoing treatment with anti PD-1 antibodies SERO does not exceed the global risk of death MESHD in this population. These results could be relevant in order to select melanoma MESHD melanoma HP therapy during the COVID-19 pandemic

    Placental pathology in COVID-19

    Authors: Elisheva D Shanes; Leena B Mithal; Sebastian Otero; Hooman A Azad; Emily S Miller; Jeffery A Goldstein

    doi:10.1101/2020.05.08.20093229 Date: 2020-05-12 Source: medRxiv

    Objectives: To describe histopathologic findings in the placentas of women with COVID-19 during pregnancy. Methods: Pregnant women with COVID-19 delivering between March 18, 2020 and May 5, 2020 were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma MESHD melanoma HP. Results: 16 placentas from patients with SARS-CoV-2 were examined (15 with live birth in the 3rd trimester 1 delivered in the 2nd trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), including abnormal or injured maternal vessels, as well as delayed villous maturation, chorangiosis, and intervillous thrombi. Rates of acute and chronic inflammation MESHD were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema MESHD edema HP and a retroplacental hematoma MESHD. Conclusions: Relative to controls, COVID-19 placentas show increased prevalence SERO of features of maternal vascular malperfusion (MVM), a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia HP. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

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MeSH Disease
Human Phenotype

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