bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of cyclotetrapeptide analogues of c-PLAI and evaluation of their antimicrobial properties
Authors: Maharani Rani , Napitupulu Orin Inggriani , Dirgantara Jelang M. , Hidayat Ace Tatang , Sumiarsa Dadan , Harneti Desi , Nurlelasari  , Supratman Unang , Fukase Koichi
Published: March 2021

Antimicrobial peptides (AMPs) are interesting compounds owing to their ability to kill several pathogens. In order to identify new AMPs, c-PLAI analogues were synthesized and evaluated together with their linear precursors for their antimicrobial properties against two Gram-positive bacteria (
Staphylococcus aureus
and
Bacillus cereus
), two Gram-negative bacteria (
Escherichia coli
and
Klebsiella pneumoniae
), and two fungal strains (
Candida albicans
and
Trichophyton mentagrophytes
). The new c-PLAI analogues were prepared through a combination of solid- and solution-phase syntheses, as previously employed for the synthesis of c-PLAI. The antimicrobial activity tests showed that the synthetic parent peptide c-PLAI was inactive or weakly active towards the bioindicators employed in the assay. The tests also indicated that cyclic c-PLAI analogues possessed enhanced antimicrobial properties against most of the bacteria and fungi tested. Furthermore, this study revealed that analogues containing cationic lysine residues displayed the highest activity towards most bioindicators. A combination of lysine and aromatic residues yielded analogues with broad-spectrum antimicrobial properties.
The effect of gold quantum dots/grating-coupled surface plasmons in inverted organic solar cells
Authors: Kuntamung Kulrisa , Yaiwong Patrawadee , Lertvachirapaiboon Chutiparn , Ishikawa Ryousuke , Shinbo Kazunari , Kato Keizo , Ounnunkad Kontad , Baba Akira
Published: March 2021

We studied the effect of gold quantum dots (AuQDs)/grating-coupled surface plasmon resonance (GC-SPR) in inverted organic solar cells (OSCs). AuQDs are located within a GC-SPR evanescent field in inverted OSCs, indicating an interaction between GC-SPR and AuQDs' quantum effects, subsequently giving rise to improvement in the performance of inverted OSCs. The fabricated solar cell device comprises an ITO/TiO
2
/P3HT : PCBM/PEDOT : PSS : AuQD/silver grating structure. The AuQDs were loaded into a hole transport layer (PEDOT : PSS) of the inverted OSCs to increase absorption in the near-ultraviolet (UV) light region and to emit visible light into the neighbouring photoactive layer, thereby achieving light-harvesting improvement of the device. The grating structures were fabricated on P3HT:PCBM layers using a nanoimprinting technique to induce GC-SPR within the inverted OSCs. The AuQDs incorporated within the strongly enhanced GC-SPR evanescent electric field on metallic nanostructures in the inverted OSCs improved the short-circuit current and the efficiency of photovoltaic devices. In comparison with the reference OSC and OSCs with only green AuQDs or only metallic grating, the developed device indicates enhancement of up to 16% power conversion efficiency. This indicates that our light management approach allows for greater light utilization of the OSCs because of the synergistic effect of G-AuQDs and GC-SPR.
The modularity of a social group does not affect the transmission speed of a novel, socially learned behaviour, or the formation of local variants
Authors: Laker Philippa R. , Hoppitt William , Weiss Michael , Madden Joah R.
Published: March 2021

The structure of a group is critical in determining how a socially learnt behaviour will spread. Predictions from theoretical models indicate that specific parameters of social structure differentially influence social transmission. Modularity describes how the structure of a group or network is divided into distinct subgroups or clusters. Theoretical modelling indicates that the modularity of a network will predict the rate of behavioural spread within a group, with higher modularity slowing the rate of spread and facilitating the establishment of local behavioural variants which can prelude local cultures. Despite prolific modelling approaches, empirical tests via manipulations of group structure remain scarce. We experimentally manipulated the modularity of populations of domestic fowl chicks,
Gallus gallus domesticus,
to affect the transmission of a novel foraging behaviour. We compared the spread of behaviour in populations with networks of high or low modularity against control populations where social transmission was prevented. We found the foraging behaviour to spread socially between individuals when the social transmission was permitted; however, modularity did not increase the speed of behavioural spread nor lead to the initial establishments of shared behavioural variants. This result suggests that factors in the social transmission process additional to the network structure may influence behavioural spread.
Accounting for uncertainty: inhibition for neural inference in the cerebellum
Authors: Palacios Ensor Rafael , Houghton Conor , Chadderton Paul
Published: March 2021

Sensorimotor coordination is thought to rely on cerebellar-based internal models for state estimation, but the underlying neural mechanisms and specific contribution of the cerebellar components is unknown. A central aspect of any inferential process is the representation of uncertainty or conversely precision characterizing the ensuing estimates. Here, we discuss the possible contribution of inhibition to the encoding of precision of neural representations in the granular layer of the cerebellar cortex. Within this layer, Golgi cells influence excitatory granule cells, and their action is critical in shaping information transmission downstream to Purkinje cells. In this review, we equate the ensuing excitation–inhibition balance in the granular layer with the outcome of a precision-weighted inferential process, and highlight the physiological characteristics of Golgi cell inhibition that are consistent with such computations.
Biomedical Discovery through the integrative Biomedical Knowledge Hub (iBKH)
Authors: Su Chang , Hou Yu , Rajendran Suraj , Maasch Jacqueline R. M. A. , Abedi Zehra , Zhang Haotan , Bai Zilong , Cuturrufo Anthony , Guo Winston , Chaudhry Fayzan F. , Ghahramani Gregory , Tang Jian , Cheng Feixiong , Li Yue , Zhang Rui , Bian Jiang , Wang Fei
Published: March 2021

The massive and continuously increasing volume of biomedical knowledge derived from biological experiments or gained from healthcare practices has become an invaluable treasure for biomedicine. The emerging biomedical knowledge graphs (BKGs) provide an efficient and effective way to manage the abundant knowledge in biomedical and life science. In the present study, we harmonized and integrated data from diverse biomedical resources to curate a comprehensive BKG, named the integrative Biomedical Knowledge Hub (iBKH). To facilitate the usage of iBKH in biomedical research, we developed a web-based, easy-to-use, publicly available graphical portal that allows fast, interactive, and visualized knowledge retrieval in iBKH. Furthermore, an efficient and scalable graph learning pipeline was developed for novel knowledge discovery in iBKH. As a proof of concept, we performed our iBKH-based method for computational in silico drug repurposing for Alzheimer’s disease. The iBKH is publicly available at: http://ibkh.ai/.
Significance testing for small annotations in stratified LD-Score regression
Authors: Tashman Katherine C. , Cui Ran , O’Connor Luke J. , Neale Benjamin M. , Finucane Hilary K.
Published: March 2021

S-LDSC is a widely used heritability enrichment method that has helped gain biological insights into numerous complex traits. It has primarily been used to analyze large annotations that contain approximately 0.5% of SNPs or more. Here, we show in simulation that, when applied to small annotations, the block jackknife-based significance testing used in S-LDSC does not always control type 1 error. We show that the inflation of type 1 error for small annotations is due both to the noisiness of the jackknife estimate of the standard error and to the non-normality of the regression coefficient estimates. We use the percent of 0.01 centimorgan blocks in the genome overlapped by the annotation to quantify the size of an annotation and the extent to which the SNPs in the annotation cluster together, and we find thresholds on this value above which type 1 error is controlled. We have implemented a test in the LDSC software that informs users when they compute LD scores for an annotation if the annotation does not pass the threshold for producing controlled type 1 error.

Author Summary

Genetics is a rapidly evolving field that allows us to link our genetic code to the physiological manifestations of disease. A key part of this work is finding regions of the genome that contribute disproportionately to the genetic underpinnings of a disease. A commonly used tool to provide such insight is stratified LD score regression (S-LDSC). S-LDSC allows us to estimate how much a set of genomic regions contributes to the overall heritability of a phenotype, and to test whether this is more than we would expect by chance. Here we show that when we apply S-LDSC to a small set of genomic regions, it does not give an accurate test of whether this set of genomic regions contributes more than we would expect by chance to the phenotype. We characterize what it means to be a “small” set of genomic regions, and we set thresholds to restrict which annotations we test to prevent false positive results.This helps to ensure that as we continue to pursue genetic analyses at scale, we report only truly significant results that will help us further understand the etiology of many of the traits we study.
Mindfulness-based intervention for very preterm young adolescents: An RCT
Authors: Siffredi Vanessa , Liverani Maria Chiara , Hüppi Petra Susan , Freitas Lorena , De Albuquerque Jiske , Gimbert Fanny , Merglen Arnaud , Meskaldji Djalel-Eddine , Tolsa Cristina Borradori , Hà-Vinh Leuchter Russia
Published: March 2021

Objectives

This randomised controlled trial (RCT) assesses the effectiveness of a Mindfulness-Based Intervention (MBI) in improving executive, behavioural and socio-emotional competences in very preterm young adolescents.

Methods

58 young adolescents aged 10 to 14 years, born before 32 gestational weeks at the Geneva University Hospital, Switzerland, participated in the study. They were randomly assigned to an “intervention” or a “waiting” group and all completed an 8-week MBI in a cross-over design. Executive, behavioural and socio-emotional competences were assessed at three different time points via parent and self-reported questionnaires, neuropsychological testing, and computerised tasks. We analysed data using an intention-to-treat approach with linear modelling. Subgroups of participants based on levels of prematurity were created using k-means clustering.

Results

Parent questionnaires revealed a statistically significant immediate effect of MBI with increased executive and behavioural competencies in everyday life. Increased executive competence was also observed on a Flanker task with enhanced speed of processing after MBI. Two subgroups of participants were created based on measures of prematurity, which revealed increased long-term benefits in the moderate-risk that are not observed in the high-risk subgroups of VPT young adolescents.

Conclusions

Our findings show a beneficial effect of MBI on executive, behavioural and socio-emotional competences in VPT young adolescents. Moderate-risk and high-risk VPT young adolescents showed different immediate and long-term beneficial effects of the intervention. Our results suggest that MBI is a valuable tool for reducing detrimental consequences of prematurity in young adolescents, especially regarding executive, behavioural and socio-emotional difficulties.

Data Sharing Statement

Deidentified individual participant data (including data dictionaries) will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted toRussia.HaVinhLeuchter@unige.ch.
Mortality and Severity in COVID-19 Patients on ACEIs & ARBs - A Meta-Regression Analysis
Authors: Singh Romil , Rathore Sawai Singh , Khan Hira , Bhurwal Abhishek , Sheraton Mack , Ghosh Prithwish , Anand Sohini , Makadia Janaki , Ayesha FNU , Mahapure Kiran S. , Mehra Ishita , Tekin Aysun , Kashyap Rahul , Bansal Vikas
Published: March 2021

Purpose

The primary objective of this review is to examine studies reporting association of mortality in COVID-19 patients with whether they were on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin II receptor blockers (ARBs). A secondary objective is to similarly access associations with higher severity of the disease in COVID-19 patients.

Materials and Methods

We searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for randomized trials and longitudinal studies from all over the world reporting mortality and severity published before January 18th, 2021. Meta-analyses were performed using 53 studies for mortality outcome and 43 for the severity outcome. Mantel-Haenszel odds ratios were generated to describe overall effect size using random effect models. To account for between study results variations, multivariate meta-Regression was performed with preselected covariates using maximum likelihood method for both the mortality and severity models.

Result

Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR=1.16 95% CI 0.94 to 1.44, p= 0.15, I2 = 93.2%) or severity (OR=1.18, 95% CI 0.94 to 1.48 p= 0.15, I2 = 91.1%) in comparison to not being on ACEIs/ARBs in COVID-19 positive patients. Multivariate meta-regression for the mortality model demonstrated that 36% of between study variations could be explained by differences in age, gender, and proportion of heart diseases in the study samples. Multivariate meta-regression for the severity model demonstrated that 8% of between study variations could be explained by differences in age, proportion of diabetes, heart disease and study country in the study samples.

Conclusion

We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.
Evaluation of the Panbio™ COVID-19 Ag Rapid Test at an Emergency Room in a Hospital in São Paulo, Brazil
Authors: Faíco-Filho Klinger Soares , Finamor Júnior Francisco Estivallet , Vinícius Leão Moreira Luiz , Lins Paulo Ricardo Gessolo , Justo Alberto Fernando Oliveira , Bellei Nancy
Published: March 2021

Introduction

The performance characteristics of the Panbio™ COVID-19 Ag test were evaluated against RT-PCR – considered the gold-standard for the detection of SARS-CoV-2 – at an emergency room in São Paulo, Brazil. The study aimed to determine the sensitivity, specificity, positive percent agreement (PPA), and negative percent agreement (NPA) as compared to RT-PCR.

Methods

Specimens from 127 suspected patients were tested by both the Panbio™ COVID-19 Ag test and by RT-PCR.

Results

Evaluation of the agreement between the Panbio™ COVID-19 Ag test and RT-PCR indicated an overall sensitivity of 84% (95%CI, 75-93.8%) and an overall specificity of 98% (95%CI, 96-98.8%). The Panbio™ COVID-19 Ag test showed 97% sensitivity and 99% NPA for subjects with Ct values ≤ 25 (N=37).

Conclusion

The Panbio™ COVID-19 Ag test is suitable for use as a diagnostic test for the rapid screening of patients presenting COVID-19 symptoms, or those suspected with being infected, prior to being admitted to hospital.
Association ofNRAMP1-INT4 gene with Susceptibility to Tuberculosis in the Sudanese Population: A Case-Control Study
Authors: Gubara Mohamed Sara Gamal , Elaagip Arwa , Salaheldin Maryam Atif , Idris Abeer Babiker , Musa Taha Hussein , Mohammed Fayad Osman , Mohammed Layla Ahmed , Musa Hassan Hussein
Published: March 2021

Background

Sudan is a Sub-Saharan African country with a high prevalence rate of Tuberculosis. Natural Resistant Associated Macrophage Protein 1 (NRAMP1) plays a potential role in the development of immunity against TB, and it has a critical role in disease resistance. The aim of the study was to evaluate the association ofNRAMP1polymorphism at intron4 (INT4) region with susceptibility to TB infection.

Methods

Demographic, clinical and microbiological data were collected from 150 participants and investigated using designed questionnaire. The genotyping ofNRAMP1-INT4 polymorphism was performed in 60 TB-infected patients and 50 healthy control using Polymerase chain reaction and restriction fragment-length polymorphism method (PCR-RFLP).

Results

Among cases (60%) were males, only (3.3%) were vaccinated. The most reported risk factors were tobacco smoking (17%), diabetes (10%), alcohol consumption (2%) and corticosteroid therapy intakes (1%). Pulmonary TB was detected in 67% of the patients, 24% had pulmonary/MDR and 9% had extra-pulmonary TB. The frequency of wild G allele was significantly higher in cases compared with healthy control subjects (P-value <0.0001). Also, a significant association was observed between the heterozygosity forNRAMP1-INT4 variant and resistance to TB infection (P-value 0.001, OR= 4.83, 95%CI 1.96∼11.88). Homozygotes mutant INT4 (C/C) genotype was not detected in both cases and controls.

Conclusions

theNRAMP1-INT4 polymorphism may serve as marker of unidentified genetic factors that may play a critical role in host immunity to TB in the Sudanese population. Further studies with large sample size are recommended to determine population-specific genetic associations with TB susceptibility in order to guide TB therapy and prophylaxis in a population-specific manner.
The Effect of Diabetes and Prediabetes on Anti-tuberculosis Treatment Outcomes: A Multicentric Prospective Cohort Study
Authors: Arriaga María B. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Nogueira Betânia , Freire Maria Vitória C.N.S. , Queiroz Artur T.L. , Rodrigues Moreno M.S. , Rocha Michael S. , Souza Alexandra B. , Spener-Gomes Renata , Carvalho Anna Cristina C. , Figueiredo Marina C. , Turner Megan M. , Durovni Betina , Lapa-e-Silva José R. , Kritski Afrânio L. , Cavalcante Solange , Rolla Valeria C. , Cordeiro-Santos Marcelo , Sterling Timothy R. , Andrade Bruno B.
Published: March 2021

Background

It is unclear whether diabetes or prediabetes drives adverse treatment outcomes and death in people with tuberculosis (PWTB).

Methods

Culture-confirmed PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (n=756) were stratified based on glycemic status by baseline glycated hemoglobin levels. Unfavorable TB outcome was defined as treatment failure or modification, recurrence or death, whereas favorable outcome was cure or treatment completion. We validated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (n=20,989). Stepwise binary multivariable regression analysis models evaluated associations between glycemic status and unfavorable outcomes.

Results

In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with drug resistance and HIV infection. Diabetes was associated with unfavorable outcomes in the RePORT (aOR: 2.85, p=0.001) and in SINAN (aOR: 1.56, p=0.040) cohorts. Furthermore, diabetes was associated with higher risk of death in both, RePORT-Brazil (aOR:3.23, p=0.006) and in the SINAN (aOR:2.75, p= 0.047) cohorts.

Conclusion

Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve tuberculosis treatment outcomes in persons with diabetes are needed.

40-word summary of the article’s main point

In a multicenter prospective cohort study from Brazil, diabetes was associated with an increased risk of unfavorable treatment outcomes, including mortality, in pulmonary tuberculosis patients. These observations were validated in the Brazilian National Disease Notification System during the same period.
Transcriptome analysis of PBMCs reveals distinct immune response in the asymptomatic and re-detectable positive COVID-19 patients
Authors: Zhang Jiaqi , Lin Dongzi , Li Kui , Ding Xiangming , Li Lin , Liu Yuntao , Liu Dongdong , Lin Jing , Teng Xiangyun , Li Yizhe , Liu Ming , Wang Xiaodan , He Dan , Shi Yaling , Wang Dawei , Xu Jianhua
Published: March 2021

The existence of asymptomatic and re-detectable positive COVID-19 patients presents the disease control challenges of COVID-19. Most studies on immune response of COVID-19 have focused on the moderately or severely symptomatic patients, however little is known about the immune response in asymptomatic and re-detectable positive patients. Here we performed a comprehensive analysis of the transcriptomic profiles of PBMCs from 48 COVID-19 patients which include 8 asymptomatic, 13 symptomatic, 15 recovering and 12 RP patients. Our analysis revealed a down-regulation of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, we observed a lower expression of the cytokines and chemokines in the PBMC of asymptomatic and symptomatic patients. In contrast, the cytokines and chemokines level in the RP patients are higher than the recovering. GSEA analysis showed the enrichment of TNFa/NF-κB and influenza infection in the RP patients compared with the recovering patients, indicating a flu-like, hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression COVID-19 disease and help the clinical management and the immunotherapy development for COVID-19.
Evaluation of albumin kinetics in mechanically ventilated patients with COVID-19 compared to those with sepsis-induced ARDS
Authors: Su Chang , Hoffman Katherine , Zhenxing Xu , Sanchez Elizabeth , Siempos Ilias , Harrington John S , Racanelli Alexandra , Plataki Maria , Wang Fei , Schenck Edward J.
Published: March 2021

COVID-19 outcomes like mortality have been associated with albumin alteration. However, it is unclear whether albumin changes in COVID-19 are pathogen specific or not. To this end, we characterized the kinetics of serum albumin in mechanically ventilated patients with COVID-19 compared to mechanically ventilated patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS). We discovered two phases of alterations in albumin levels during the course of Covid-19 critical illness, but not for the sepsis-induced ARDS. Our findings suggest the metabolic effects of COVID-19 are pathogen-specific and albumin recovery may signal the cessation of a deleterious immune response in this disease.
Validation of breath biomarkers for obstructive sleep apnea
Authors: Nowak Nora , Engler Anna , Thiel Sira , Stöberl Anna S. , Sinues Pablo , Zenobi Renato , Kohler Malcolm
Published: March 2021

Background and objectives

Obstructive sleep apnea (OSA) is an underdiagnosed respiratory disease with negative metabolic and cardiovascular effects. The current gold standard for diagnosing OSA is in-hospital polysomnography, a time-consuming and costly procedure, often inconvenient for the patient. Recent studies revealed evidence for the potential of breath analysis for the diagnosis of OSA based on a disease-specific metabolic pattern. However, none of these findings were validated in a larger and broader cohort, an essential step for its application in clinics.

Methods

In the present study, we validated a panel of breath biomarkers in a cohort of patients with possible OSA (N = 149). These markers were previously identified in our group by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).

Results

Here, we could confirm significant differences between metabolic patterns in exhaled breath from OSA patients compared to control subjects without OSA as well as the association of breath biomarker levels with disease severity. Our prediction of the diagnosis for the patients from this completely independent validation study using a classification model trained on the data from the previous study resulted in an area under the receiver operating characteristic curve of 0.66, which is comparable to questionnaire-based OSA screenings.

Conclusions

Thus, our results suggest that breath analysis by SESI-HRMS could be used to screen for OSA. Its true predictive power should be tested in combination with OSA screening questionnaires.

Clinical trial

“Mass Spectral Fingerprinting in Obstructive Sleep Apnoea”, NCT02810158, www.ClinicalTrials.gov
Empirical networks for localized COVID-19 interventions using WiFi infrastructure at university campuses
Authors: Das Swain Vedant , Xie Jiajia , Madan Maanit , Sargolzaei Sonia , Cai James , De Choudhury Munmun , Abowd Gregory D. , Steimle Lauren N. , Prakash B. Aditya
Published: March 2021

Infectious diseases, like COVID-19, pose serious challenges to university campuses, which typically adopt closure as a non-pharmaceutical intervention to control spread and ensure a gradual return to normalcy. Intervention policies, such as remote instruction (RI) where large classes are offered online, reduce potential contact but also have broad side-effects on campus by hampering the local economy, students’ learning outcomes, and community wellbeing. In this paper, we demonstrate that university policymakers can mitigate these tradeoffs by leveraging anonymized data from their WiFi infrastructure to learn community mobility —- a methodology we refer to as WiFi mobility models (WiMob). This approach enables policymakers to explore more granular policies like localized closures (LC). WiMob can construct contact networks that capture behavior in various spaces, highlighting new potential transmission pathways and temporal variation in contact behavior. Additionally, WiMob enables us to design LC policies that close super-spreader locations on campus. By simulating disease spread with contact networks from WiMob, we find that LC maintains the same reduction in cumulative infections as RI while showing greater reduction in peak infections and internal transmission. Moreover, LC reduces campus burden by closing fewer locations, forcing fewer students into completely online schedules, and requiring no additional isolation. WiMob can empower universities to conceive and assess a variety of closure policies to prevent future outbreaks.
Exhaustive circulating tumor DNA sequencing reveals the genomic landscape of Hodgkin lymphoma and facilitates ultrasensitive detection of minimal residual disease
Authors: Sobesky Sophia , Mammadova Laman , Cirillo Melita , Drees Esther , Mattlener Julia , Dörr Helge , Altmüller Janine , Shi Zhiyuan , Bröckelmann Paul J , Weiss Jonathan , Kreissl Stefanie , Sasse Stephanie , Ullrich Roland T , Reinke Sarah , Klapper Wolfram , Gerhard-Hartmann Elena , Rosenwald Andreas , Roemer Margaretha GM , Nürnberg Peter , Hagenbeek Anton , Zijlstra Josée M. , Pegtel Dirk Michiel , Engert Andreas , Borchmann Peter , von Tresckow Bastian , Borchmann Sven
Published: March 2021

Individualizing treatment is key to improve outcome and reduce long-term side-effects in any cancer. In Hodgkin lymphoma (HL), individualization of treatment is hindered by a lack of genomic characterization and technology for sensitive, molecular response assessment.

Sequencing of cell-free (cf)DNA is a powerful strategy to understand an individual cancer genome and can be used to develop assays for extremely sensitive disease monitoring. In HL, a high proportion of cfDNA is tumor-derived making it a highly relevant disease model to study the role of cfDNA sequencing in cancer.

Here, we introduce our targeted cfDNA sequencing platform and present the largest genomic landscape of HL to date, which was entirely derived by cfDNA sequencing. We comprehensively genotype and assess minimal residual disease in 324 samples from 121 patients, presenting an integrated landscape of mutations and copy number variations in HL. In addition, we perform a deep analysis of mutational processes driving HL, investigate the clonal structure of HL and link several genotypes to HL phenotypes and outcome. Finally, we show that minimal residual disease assessment by repeat cfDNA sequencing as early as a week after treatment initiation is feasible and predicts overall treatment response allowing highly improved treatment guidance and relapse prediction. Our study also serves as a blueprint showcasing the utility of our platform for other cancers with similar therapeutic challenges.
Smoking methylation marks for prediction of urothelial cancer risk
Authors: Yu Chenglong , Jordahl Kristina M. , Bassett Julie K. , Joo Jihoon Eric , Wong Ee Ming , Brinkman Maree , Schmidt Daniel , Bolton Damien , Makalic Enes , Brasky Theodore M. , Shadyab Aladdin H. , Tinker Lesley , Longano Anthony , Hopper John L. , English Dallas R. , Milne Roger L. , Bhatti Parveen , Southey Melissa C. , Giles Graham G. , Dugué Pierre-Antoine
Published: March 2021

Background

Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction.

Methods

Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples,N=404 pairs from the Melbourne Collaborative Cohort Study (MCCS) andN=440 pairs from the Women’s Health Initiative (WHI) cohort, respectively. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication datasets using the area under the curve (AUC).

Results

The meta-analysis identified associations (P<4.7×10−5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P<0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication dataset in MCCS (N=134, odds ratio per SD [OR]=1.37, 95%CI=1.00-1.90) after confounder adjustment; AUC=0.66, compared with AUC=0.64 without methylation information. Limited evidence of replication was found in the second testing dataset in WHI (N=440, OR=1.09, 95%CI=0.91-1.30).

Conclusions

Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger datasets.

Impact

DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.
Educational attainment as a modifier of the effect of polygenic scores for cardiovascular risk factors: cross-sectional and prospective analysis of UK Biobank
Authors: Carter Alice R , Harrison Sean , Gill Dipender , Smith George Davey , Taylor Amy E , Howe Laura D , Davies Neil M
Published: March 2021

Background

Understanding the interplay between educational attainment and genetic predictors of cardiovascular risk may improve our understanding of mechanisms relating educational attainment to cardiovascular disease.

Methods

In up to 320 120 UK Biobank participants of White British ancestry (mean age = 57, female 54%), we created polygenic scores for nine cardiovascular risk factors or diseases: alcohol consumption, body mass index, low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes and stroke. We estimated whether educational attainment modified genetic susceptibility to these risk factors and diseases.

Results

On the additive scale, higher educational attainment reduced genetic susceptibility to higher BMI, smoking, atrial fibrillation and type 2 diabetes, but increased genetic susceptibility to higher LDL-C and higher systolic blood pressure.

On the multiplicative scale, there was evidence that higher educational attainment increased genetic susceptibility to atrial fibrillation and coronary heart disease, but no evidence of effect modification was found for all other considered traits.

Conclusions

Educational attainment modifies the genetic susceptibility to some cardiovascular risk factors and diseases. The direction of this effect was mixed across traits considered and differences in associations between the effect of the polygenic score across strata of educational attainment was uniformly small. Therefore, any effect modification by education of genetic susceptibility to cardiovascular risk factors or diseases is unlikely to contribute substantially to the mechanisms driving inequalities in cardiovascular risk.

Key Messages

The role of educational attainment in modifying the effect of polygenic scores for a wide range of cardiovascular risk factors or diseases has not previously been studied

We explore whether educational attainment modifies the effects of polygenic susceptibility to alcohol consumption, body mass index, low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes and stroke

Effect modification by education was observed for some cardiovascular polygenic scores, but not all.

Effects were not always in the hypothesised direction and were dependent on the scale of analysis.

Modification of the effect of genetic susceptibility to cardiovascular risk factors or cardiovascular disease by educational attainment is unlikely to contribute substantially to the mechanisms driving inequalities in cardiovascular risk.
Head-to-head performance comparison of self-collected nasal versus professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test
Authors: Klein Julian A.F. , Krüger Lisa J. , Tobian Frank , Gaeddert Mary , Lainati Federica , Schnitzler Paul , Lindner Andreas K. , Nikolai Olga , Knorr B. , Welker A. , de Vos Margaretha , Sacks Jilian A. , Escadafal Camille , Denkinger Claudia M. ,   for the study team
Published: March 2021

Background

In 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies demonstrated for SARS-CoV-2 Ag-RDTs nasal sampling to be a comparable and reliable alternative for nasopharyngeal (NP) sampling.

Methods

We conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio Ag-RDT (the second WHO-listed SARS-CoV-2 Ag-RDT, distributed by Abbott). We calculated positive and negative percent agreement and, compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR), sensitivity and specificity for both sampling techniques.

Results

A SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0% - 94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5% - 99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2% - 92.3%) and 88.9% (40/45; CI 76.5% - 95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1% - 99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log10 SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7% - 99.8%) for both, NMT and NP sampling.

Conclusion

For the Panbio Ag-RDT supervised NMT self-sampling yields to results comparable to NP sampling. This suggests that nasal self-sampling could be used for scale-up population testing.
COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review Update
Authors: Dugas Michèle , Stéfan Théo , Lépine Johanie , Blouin Patrick , Poirier Andrée-Anne , Carnovale Valérie , Mailhot Benoit , Skidmore Becky , Faust Lena , Costello Carrie , Thomson Donna , Majnemer Annette , Goldowitz Dan , Miller Steven P. , LeBlanc Annie
Published: March 2021

Objective

Information regarding the impact of COVID-19 in children with brain-based disabilities, or those at risk of developing such conditions, remains scarce. The objective was to evaluate if children with brain-based disabilities are more likely to (1) develop COVID-19, (2) develop complications from the disease, and (3) to have a poorer prognosis.

Study design

We conducted a rapid review using search strategies iteratively developed and tested by an experienced medical information specialist in consultation with the review team and a panel of knowledge users. Searches were initially performed on April 18th, 2021, and updated on October 31st, 2020. Four reviewers individually performed study selection using pilot-tested standardized forms. Single reviewers extracted the data using a standardized extraction form that included study characteristics, patients’ characteristics, and outcomes reported.

Results

We identified 1448 publications, of which 29 were included. Studies reported data on 2288 COVID-19 positive children, including 462 with a brain-based disability, and 72 at risk of developing such disability. Overall, the included studies showed a greater risk to develop severe COVID-19 disease in children with brain-based disabilities. Although mortality is very low, the case-fatality rate appeared to be higher in children with disabilities compared to children without disabilities.

Conclusions

Our review shows that children with brain-based disabilities are overrepresented in hospitalization numbers compared to children without disabilities. However, most studies included children that were hospitalized from COVID-19 in secondary and tertiary care centers. Results of this review should therefore be interpreted with caution.
Background rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments
Authors: Sundaram Maria , Nasreen Sharifa , Calzavara Andrew , He Siyi , Chung Hannah , Bronskill Susan E. , Buchan Sarah A. , Tadrous Mina , Tanuseputro Peter , Wilson Kumanan , Wilson Sarah , Kwong Jeffrey C.
Published: March 2021

Background

Nursing home (NH) residents are prioritized for COVID-19 vaccination. We report monthly mortality, hospitalizations, and emergency department (ED) visit incidence rates (IRs) during 2010-2020 to provide context for COVID-19 vaccine safety assessments.

Methods

We observed outcomes among NH residents using administrative databases. IRs were calculated by month, sex, and age group. Comparisons between months were assessed using one-sample t-tests; comparisons by age and sex were assessed using chi-squared tests.

Results

From 2010-2019, there were 83,453 (SD: 652.4) NH residents per month, with an average of 2.3 (SD: 0.28) deaths, 3.1 (SD: 0.16) hospitalizations, and 3.6 (SD: 0.17) ED visits per 100 residents per month. From March to December 2020, mortality IRs were increased, but hospitalization and ED visit IRs were reduced (p<0.05).

Conclusion

We identified consistent monthly mortality, hospitalization, and ED visit IRs during 2010-2019. Marked differences in these rates were observed during 2020, coinciding with the COVID-19 pandemic.
Enhancing Histopathological Colorectal Cancer Image Classification by using Convolutional Neural Network
Authors: Al.Shawesh Radwan , Chen Yi Xiang
Published: March 2021

Colorectal cancer (CRC) also known as bowl cancer is one of the leading death causes worldwide. Early diagnosis has become vital for a successful treatment. Now days with the new advancements in Convolutional Neural networks (CNNs) it’s possible to classify different images of CRC into different classes. Today It is crucial for physician to take advantage of the new advancement’s in deep learning, since classification methods are becoming more and more accurate and efficient. In this study, we introduce a method to improve the classification accuracy from previous studies that used the National Center for Tumor diseases (NCT) data sets. We adapt the ResNet-50 model in our experiment to classify the CRC histopathological images. Furthermore, we utilize transfer learning and fine-tunning techniques to improve the accuracy. Our Experiment results show that ResNet_50 network is the best CNN architecture so far for classifying CRC histopathological images on the NCT Biobank open source dataset. In addition to that using transfer learning allow us to obtain 97.7% accuracy on the validation dataset, which is better than all previous results we found in literature.
The tumor burden of metastatic colorectal cancer patients at initial diagnosis, pre- versus post-Covid-19 lockdown
Authors: Thierry AR , Pastor B , Pisareva E , Ghiringhelli F , Bouche O , De La Fouchardière C , Vanbockstael J , Smith D , François E , Dos Santos M , Botsen D , Ellis S , Fonck M , Andre T , Guardiola E , Khemissa F , Linot B , Martin-Babau J , Rinaldi Y , Assenat E , Clavel L , Dominguez S , Gavoille C , Sefrioui D , Pezzella V , Mollevi C , Ychou M , Mazard T
Published: March 2021

Background

The COVID-19 pandemic led to a significant reduction in the provision of screening, case identification and hospital referrals to cancer patients. To our knowledge, no study has yet correlated quantitatively the consequences of these limitations for cancer patient management. This study evaluates the implications of such reductions for patients newly diagnosed with metastatic colorectal cancer (mCRC) in both the pre- and post-lockdown periods.

Methods

We examined 80 newly identified mCRC patients from 18 different clinical centers. These cases come from the screening procedure of a clinical trial which is using circulating DNA (cirDNA) analysis to determine their RAS and BRAF status.

Results

The tumor burden as evaluated by the median total plasma cirDNA concentration showed a statistically higher level in patients diagnosed post-lockdown compared to those diagnosed pre-lockdown (119.2 versus 17.3 ng/mL; p<0.0001). In order to link tumor burden to survival, we compared the survival of these mCRC patients with previous studies in which cirDNA was examined in the same way (median survival, 16.2 months; median follow up, 48.7 months, N=135). Given the poor survival rate of mCRC patients with high cirDNA levels (14.7 vs 20.0 and 8.8 vs 19.3 months median survival when dichotomizing the cohort by the median cirDNA concentration 24.4 and 100 ng/mL, respectively), our study points to the potential deleterious consequences of the COVID-19 pandemic.

Conclusions

Recognizing that our exploratory study offers a snapshot of an evolving situation, our observations nonetheless clearly highlight the need to determine actions which would minimize delays in diagnosis during the ongoing and future waves of COVID-19.
A SIRD model applied to COVID-19 dynamics and intervention strategies during the first wave in Kenya
Authors: Ogana Wandera , Juma Victor Ogesa , Bulimo Wallace D.
Published: March 2021

The first case of COVID-19 was reported in Kenya in March 2020 and soon after non-pharmaceutical interventions (NPIs) were established to control the spread of the disease. The NPIs consisted, and continue to consist, of mitigation measures followed by a period of relaxation of some of the measures. In this paper, we use a deterministic mathematical model to analyze the dynamics of the disease, during the first wave, and relate it to the intervention measures. In the process, we develop a new method for estimating the disease parameters. Our solutions yield a basic reproduction number, R0 = 2.76, which is consistent with other solutions. The results further show that the initial mitigation reduced disease transmission by 40% while the subsequent relaxation increased transmission by 25%. We also propose a mathematical model on how interventions of known magnitudes collectively affect disease transmission rates. The modelled positivity rate curve compares well with observations. If interventions of unknown magnitudes have occurred, and data is available on the positivity rate, we use the method of planar envelopes around a curve to deduce the modelled positivity rate and the magnitudes of the interventions. Our solutions deduce mitigation and relaxation effects of 42.5% and 26%, respectively; these percentages are close to values obtained by the solution of the SIRD system. Our methods so far apply to a single wave; there is a need to investigate the possibility of extending them to handle multiple waves.
COVID-19 risk perception and vaccine acceptance in individuals with chronic disease
Authors: Smith Brianna A. , Ricotta Emily E. , Kwan Jennifer L. , Evans Nicholas G.
Published: March 2021

Background

COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of non-pharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions.

Methods

We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors.

Results

In the initial survey, individuals reporting a chronic disease had stronger both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls.

Conclusions

It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized.