bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity paradox in patients with cancer: A systematic review and meta-analysis of 6,320,365 patients
Authors: Petrelli Fausto , Cortellini Alessio , Indini Alice , Tomasello Gianluca , Ghidini Michele , Nigro Olga , Salati Massimiliano , Dottorini Lorenzo , Iaculli Alessandro , Varricchio Antonio , Rampulla Valentina , Barni Sandro , Cabiddu Mary , Bossi Antonio , Ghidini Antonio , Zaniboni Alberto 
Published: May 2020

AbstractBACKGROUNDObesity, defined as a body mass index (BMI) > 30 kg/m2, is associated with a significant increase in risk of many cancers. In last years, various studies suggested that obese cancer patients have better outcomes than non-obese patients. This phenomenon, also known as “the obesity paradox”, is not well understood and presents controversial explanations. We performed a systematic review and meta-analysis to assess the association between obesity and outcome after a diagnosis of cancer.PATIENTS AND METHODSPubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020, for studies reporting prognosis of patients with obesity and cancer. Risk of death, cancer-specific survival (CSS) and progression were pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI). The primary outcome of the study refers to overall survival (OS) in obese vs non-obese patients with malignancies. Secondary endpoints were CSS and progression- or disease-free survival (PFS or RFS).RESULTSMortality and relapse associated with obesity in patients with cancer were evaluated among n=6,320,365 participants (n=203 studies). Overall, association of obesity and cancer was associated with a reduced OS (HR =1.14, 95% CI: 1.09-1.19; P<.01) and CSS (HR=1.17, 95%CI 1.12-1.23; P<.01). Patients were also at increased risk for relapse (HR=1.13, 95%CI 1.07-1.19; P<.01). Patients with breast, colorectal and uterine tumors were at increased risk of death. Conversely, obese with lung cancer, renal cell carcinoma and melanoma survived longer that non-obese.CONCLUSIONSIn many cancer patients, obesity reduces survival and increases the risk of relapse. In lung cancer, renal cell carcinoma and melanoma obesity was protective in terms of outcome. More intensive follow up, adequate dosing of oncological treatments, calories intake restrictions, physical activity and monitoring of obesity-related complications are effective measures for reducing mortality in these subjects.
A possible role of immunopathogenesis in COVID-19 progression
Authors: Anft Moritz , Paniskaki Krystallenia , Blazquez-Navarro Arturo , Doevelaar Adrian , Seibert Felix S. , Hoelzer Bodo , Skrzypczyk Sarah , Kohut Eva , Kurek Julia , Zapka Jan , Wehler Patrizia , Kaliszczyk Sviatlana , Bajda Sharon , Thieme Constantin J. , Roch Toralf , Justine Konik Margarethe , Brenner Thorsten , Tempfer Clemens , Watzl Carsten , Dolff Sebastian , Dittmer Ulf , Westhoff Timm H. , Witzke Oliver , Stervbo Ulrik , Babel Nina 
Published: May 2020

AbstractBackgroundThe efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities.MethodsIn this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity.ResultsSignificantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression.ConclusionOur data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.
Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers
Authors: Xiao Tongyang , Wang Yanrong , Yuan Jing , Ye Haocheng , Wei Lanlan , Liao Xuejiao , Wang Haiyan , Qian Shen , Wang Zhaoqin , Liu Lei , Zhang Zheng 
Published: May 2020

AbstractBackgroundAsymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear.MethodsA total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay.ResultsAmong 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05).ConclusionYoung COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.
CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties
Authors: Arneson Douglas , Elliott Matthew , Mosenia Arman , Oskotsky Boris , Vashisht Rohit , Zack Travis , Bleicher Paul , Butte Atul J. , Rudrapatna Vivek A. 
Published: May 2020

AbstractManagement of the COVID-19 pandemic has proven to be a significant challenge to policy makers. This is in large part due to uneven reporting and the absence of open-access visualization tools to present local trends and infer healthcare needs. Here we report the development of CovidCounties.org, an interactive web application that depicts daily disease trends at the level of US counties using time series plots and maps. This application is accompanied by a manually curated dataset that catalogs all major public policy actions made at the state-level, as well as technical validation of the primary data. Finally, the underlying code for the site is also provided as open source, enabling others to validate and learn from this work.
Modifiable and non-modifiable risk factors for COVID-19: results from UK Biobank
Authors: Ho Frederick K , Celis-Morales Carlos A , Gray Stuart R , Katikireddi S Vittal , Niedzwiedz Claire L , Hastie Claire , Lyall Donald M , Ferguson Lyn D , Berry Colin , Mackay Daniel F , Gill Jason MR , Pell Jill P , Sattar Naveed , Welsh Paul 
Published: May 2020

AbstractBackgroundInformation on risk factors for COVID-19 is sub-optimal. We investigated demographic, lifestyle, socioeconomic, and clinical risk factors, and compared them to risk factors for pneumonia and influenza in UK Biobank.MethodsUK Biobank recruited 37–70 year olds in 2006–2010 from the general population. The outcome of confirmed COVID-19 infection (positive SARS-CoV-2 test) was linked to baseline UK Biobank data. Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes.FindingsAmong 428,225 participants, 340 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index (RR 1.24 per SD increase), smoking (RR 1.38), slow walking pace as a proxy for physical fitness (RR 1.66) and use of blood pressure medications as a proxy for hypertension (RR 1.40). Non-modifiable risk factors included older age (RR 1.10 per 5 years), male sex (RR 1.64), black ethnicity (RR 1.86), socioeconomic deprivation (RR 1.26 per SD increase in Townsend Index), longstanding illness (RR 1.38) and high cystatin C (RR 1.24 per 1 SD increase). The risk factors overlapped with pneumonia somewhat; less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza.InterpretationThese findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk.FundingBritish Heart Foundation, Medical Research Council, Chief Scientist Office.
Anosmia in COVID-19 patients
Authors: Hornuss Daniel , Lange Berit , Schröter Nils , Rieg Siegbert , Kern Winfried V. , Wagner Dirk 
Published: May 2020

AbstractObjectivesCoronaviruses (CoVs) have a neuroinvasive propensity, and the frequently reported symptoms of smelling and taste dysfunction in many COVID-19 patients may be related to the respective capability of SARS-CoV2, the cause of the current pandemic. In this study we objectified and quantified the magnitude and underreporting of the smelling dysfunction caused by COVID-19 using a standardized test.MethodsWe conducted a prospective cross-sectional study comparing the proportion of anosmia using Sniffin-sticks in those reporting a loss of smell, in those who did not as well as in uninfected controls. The outcome of anosmic versus not anosmic patients were recorded during hospital stay and at day 15 on a six-category ordinal scale. The study was approved by the institutional review board, all participants consented to the study.Results40% of 45 consecutive hospitalized COVID-19 patients and 0% of 45 uninfected controls consenting were diagnosed with anosmia. 44% of anosmic and 50% of hyposmic patients did not report having smelling problems. Anosmia or hyposmia was not predictive of a severe COVID-19 manifestation.ConclusionsThe majority of COVID-19 patients have an objective anosmia and hyposmia, which often occurs unnoticed. These symptoms may be related to the neuroinvasive propensity of SARS-COV-2 and the unusual presentation of COVID-19 disease manifestations.
Releasing the lockdown in the UK Covid-19 epidemic: a stochastic model
Authors: Lander Anthony 
Published: May 2020

AbstractBackgroundIn a classic epidemic, the infected population has an early exponential phase, before slowing and fading to its peak. Mitigating interventions may change the exponent during the rising phase and a plateau can replace a peak. With interventions comes the risk that relaxation causes a second-wave. In the UK Covid-19 epidemic, infections cannot be counted, but their influence is seen in the curve of the mortality data. This work simulated social distancing and the lockdown in the UK Covid-19 epidemic to explore strategies for relaxation.MethodsCumulative mortality data was transposed 20 days earlier to identify three doubling periods separated by the 17th March—social distancing, and 23rd March—lockdown. A set of stochastic processes simulated viral transmission between interacting individuals using Covid-19 incubation and illness durations. Social distancing and restrictions on interactions were imposed and later relaxed.Principal FindingsDaily mortality data, consistent with that seen in the UK Covid-19 epidemic to 24th April 2020 was simulated. This output predicts that under a lockdown maintained till early July 2020, UK deaths will exceed 31,000, but leave a large susceptible population and a requirement for vaccination or quarantine. An earlier staged relaxation carries a risk of a second-wave. The model allows exploration of strategies for lifting the lockdown.InterpretationSocial distancing and the lockdown have had an impressive impact on the UK Covid-19 epidemic and saved lives, caution is now needed in planning its relaxation.FundingUnfunded research.Research in contextEvidence before this studyThe classical Susceptible, Infected, Recovered, (SIR) epidemiological model with additional compartments and sophistications have been widely used to make forecasts in the Covid-19 pandemic but are not easily accessible.Added value of this studyThis study adds reassurance that the interventions of social distancing introduced on the 17th March and the lockdown of the 23rd March 2020 have reduced mortality. The risks of a second-wave on their relaxation are real and illustrated graphically.Implications of all the available evidenceTogether with other models, credence is given to the risks of a second-wave in the UK Covid-19 epidemic on the relaxation of restrictions.
A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilised in a commercial dual-target diagnostic assay
Authors: Artesi Maria , Bontems Sébastien , Göbbels Paul , Franckh Marc , Maes Piet , Boreux Raphaël , Meex Cécile , Melin Pierrette , Hayette Marie-Pierre , Bours Vincent , Durkin Keith 
Published: May 2020

AbstractControl of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of qRT-PCR assays have been developed to identify SARS-CoV-2, targeting multiple positions in the viral genome. While the mutation rate of SARS-CoV-2 is moderate, given the large number of transmission chains it is prudent to monitor circulating viruses for variants that might compromise these assays. Here we report the identification of a C-to-T transition at position 26,340 of the SARS-CoV-2 genome which is associated with failure of the cobas® SARS-CoV-2 E-gene qRT-PCR in eight patients. As the cobas® SARS-CoV-2 assay targets two positions in the genome, the individuals carrying this variant were still called as SARS-CoV-2 positive. Whole genome sequencing of SARS-CoV-2 showed all to carry closely related viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently at least four times. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect RT-PCRs used in diagnostics. Additionally, it argues that two regions in SARS-CoV-2 should be targeted to avoid false negatives.
Ocular toxicity and Hydroxychloroquine: A Rapid Meta-Analysis
Authors: Michelson Matthew , Chow Tiffany , Martin Neil , Ross Mike , Tee Amelia , Minton Steven 
Published: May 2020

AbstractRapid access to evidence is crucial in times of evolving clinical crisis. To that end, we propose a novel mechanism to answer clinical queries: Rapid Meta-Analysis (RMA). Unlike traditional meta-analysis, RMA balances quick time-to-production with reasonable data quality assurances, leveraging Artificial Intelligence to strike this balance. This article presents an example RMA to a currently relevant clinical question: Is ocular toxicity and vision compromise a side effect with hydroxychloroquine therapy?As of this writing, hydroxychloroquine is a leading candidate in the treatment of COVID-19. By combining AI with human analysis, our RMA identified 11 studies looking at ocular toxicity as a side effect and estimated the incidence to be 3.4% (95% CI: 1.11-9.96%). The heterogeneity across the individual study findings was high, and interpretation of the result should take this into account. Importantly, this RMA, from search to screen to analysis, took less than 30 minutes to produce.
Identification of Three Endotypes in Pediatric Acute Respiratory Distress Syndrome by Nasal Transcriptomic Profiling
Authors: Williams James Garrett , Joshi Rashika , Jones Rhonda , Yunger Toni , Stoneman Erin , Varisco Brian 
Published: May 2020

1ABSTRACTAcute respiratory distress syndrome (ARDS) and pediatric ARDS (PARDS) can be triggered by multiple pulmonary and non-pulmonary insults and are the source of substantial morbidity and mortality. The nasal epithelium is similar to that of the lower conducting airways and nasal transcriptomic profiling identifies disease and endotypes in lung cancer, COPD, and asthma. We conducted a prospective trial of testing whether this technique could identify PARDS endotypes in 26 control and 25 PARDS subjects <18 admitted to the PICU extracting RNA from inferior turbinate brushings on days 1, 3, 7, and 14. Standard RNA processing and mRNA-seq yielded ~25% usable specimens and a modified, low-input RNA protocol yielded 95% usable specimens. Sixty-four low-input specimens from 10 control and 15 PARDS subjects were used for initial analysis. Control and some PARDS subjects clustered together in both by-day and combined analysis into Groups A while some day 1, 3, and 7 specimens from the same subjects clustered into Groups B and C with specimens from these subjects moving to Group A with PARDS resolution. In multivariate analysis, the only clinical variables predictive of Group B or C status was severity of lung injury or viral PARDS trigger. Compared to Group A, Group B had upregulation of innate immune processes and group C had upregulation of cilia-associated processes. Analysis of the 15 specimens processed and analyzed by standard techniques identified the same processes as differentiating Groups A, B, and C. Mortality appeared to be higher in group B (25%) and C subjects (28.6%) compared to A subject (5%, p=0.1). Our findings demonstrate three distinct PARDS endotypes which may be useful for prognostic and therapeutic enrichment. ClinicalTrials.gov Identifier NCT03539783
FOXP3 mRNA profile prognostic of T cell mediated rejection and human kidney allograft survival
Authors: Luan Danny , Dadhania Darshana M. , Ding Ruchuang , Muthukumar Thangamani , Lubetzky Michelle , Lee John R. , Sharma Vijay K. , August Phyllis , Mueller Franco B. , Schwartz Joseph E. , Suthanthiran Manikkam 
Published: May 2020

AbstractBackground and objectivesT cell mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes fail to respond to anti-rejection therapy. FOXP3 is a specification factor for regulatory T cells and our single center study of 83 kidney allograft recipients showed that urinary cell FOXP3 mRNA level is diagnostic of TCMR and predicts TCMR reversibility and allograft survival. The objective of the current study is to determine whether our original findings could be replicated in an independent cohort of 480 kidney allograft recipients enrolled in the multicenter Clinical Trials of Organ Transplantation (CTOT)-04.Design, setting, participants, and measurementsWe measured levels of FOXP3 mRNA and levels of mRNA for CD25, CD3E, and perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in CTOT-04. RNA was isolated from the urinary cells and preamplification-enhanced real-time quantitative PCR assays were used to measure mRNAs.Results18S rRNA normalized levels of mRNA for FOXP3 (P=0.01, Kruskal-Wallis test), CD25 (P=0.01), CD3E (P<0.0001), and perforin (P<0.0001) distinguished patients with TCMR biopsies from those with No Rejection biopsies and those with stable graft function. FOXP3 mRNA level, but not the levels of mRNA for CD25, CD3E, or perforin, predicted TCMR reversal (AUC=0.764; 95% confidence interval, 0.611 to 0.917; P=0.008). Multivariable logistic regression analysis showed that FOXP3 mRNA level remains predictive after adjustment for potential cofounders. Kaplan-Meier survival curve analysis showed that FOXP3 mRNA level (P=0.0306) but not the levels of mRNA for CD25, CD3E, or perforin, is associated with kidney allograft survival.ConclusionIn the independent CTOT-04 cohort, we demonstrate that urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts its reversibility, and is prognostic of kidney allograft survival following an episode of TCMR.
Proteogenomics of glioblastoma associates molecular patterns with survival
Authors: Yanovich-Arad Gali , Ofek Paula , Yeini Eilam , Danilevsky Artem , Shomron Noam , Grossman Rachel , Satchi-Fainaro Ronit , Geiger Tamar 
Published: May 2020

SummaryGlioblastoma (GBM) is the most aggressive form of glioma, with poor prognosis exhibited by most patients, and a median survival time of less than two years. To examine survival-associated patterns, we assembled a cohort of 87 GBM patients whose survival ranges from less than 3 months and up to 10 years, most of which are not bearing isocitrate-dehyderogenase (IDH)-1 mutation and did not undergo prior treatment. We integrated high-resolution mass-spectrometry proteomics and RNA-sequencing to examine the yet unresolved proteomic contribution to poor patient outcome, and compared it to the more established transcriptomic contribution and to published single-cell RNA-sequencing data. Discovering both layer-specific and shared processes, we found that immune, metabolic and developmental processes distinguish short and long survival periods. Additionally, we observed a significant discrepancy in tumor classification between expression layers. Overall, our integrative findings establish proteomic heterogeneity in GBM as a gateway to understanding poor patient survival.
Molecular detection of SARS-CoV-2 using a reagent-free approach
Authors: Calvez Ronan , Taylor Andrew , Calvo-Bado Leo , Fink Colin 
Published: May 2020

AbstractShortage of reagents and consumables required for the extraction and molecular detection of SARS-CoV-2 RNA in respiratory samples has led many laboratories to investigate alternative approaches for sample preparation. Fomsgaard et al 20205 recently presented results using heat-processing of respiratory samples prior to RT-qPCR as an economical method enabling an extremely fast streamlining of the processes at virtually no cost.Here, we present our results using this method and highlight some major pitfalls that diagnostics laboratories should be aware of before proceeding with this technique. We first investigated various treatments using different temperatures, incubation times and sample volumes based on the above study to optimise the heat-treatment conditions. Although the initial data confirmed the published results, further investigations revealed unexpected inhibitory properties of some commonly used virus transport media (VTMs) on some commercially available RT-qPCR mixes, emphasising the critical importance of a thorough validation process to determine the most adapted reagents to be used depending on the sample types to be tested.In conclusion, although the method works, with very consistent Ct values and an excellent sensitivity when compared to a conventional RNA extraction method, it is critical to include an internal control to check each sample for potential inhibition.