AimsIn May 2020, a nationwide, web-based system for remote entry of patient-reported outcomes (PROs) in inflammatory rheumatic diseases was launched and implemented in routine care ...(DANBIO-from-home). After 1.5 years of use, we explored clinical characteristics of patients who did versus did not use the system, and the time to first entry of PROs.MethodsAll patients followed in DANBIO were informed about DANBIO-from-home by electronic invitations or when attending their clinic. Characteristics of patients who did/did not use DANBIO-from-home in the period after implementation were explored by multivariable logistic regression analyses including demographic and clinical variables (gender, age group, diagnosis, disease duration, use of biological disease-modifying agent (bDMARD), Health Assessment Questionnaire (HAQ), Patient Acceptable Symptom Scale (PASS)). Time from launch to first entry was presented as cumulative incidence curves by age group (<40/40–60/61–80/>80 years).ResultsOf 33 776 patients, 68% entered PROs using DANBIO-from-home at least once. Median (IQR) time to first entry was 27 (11–152) days. Factors associated with data entry in multivariate analyses (OR (95% CI)) were: female gender (1.19 (1.12 to 1.27)), bDMARD treatment (1.41 (1.33 to 1.50)), age 40–60 years (1.79 (1.63 to 1.97)), 61–80 years (1.87 (1.70 to 2.07), or age >80 years (0.57 (0.50 to 0.65)) (reference: age <40 years), lower HAQ (0.68 (0.65 to 0.71)) and PASS ‘no’ (1.09 (1.02 to 1.17). Diagnosis was not associated. Time to first entry of PROs was longest in patients <40 years of age (119 (24–184) days) and shortest in the 61–80 years age group (25 (8–139) days).ConclusionA nationwide online platform for PRO in rheumatology achieved widespread use. Higher age, male gender, conventional treatment and disability were associated with no use.
Post-transcriptional regulation of gene expression by small RNAs and RNA binding proteins is of fundamental importance in development of complex organisms, and dysregulation of regulatory RNAs can ...influence onset, progression and potentially be target for treatment of many diseases. Post-transcriptional regulation by small RNAs is mediated through partial complementary binding to messenger RNAs leaving nucleotide signatures or motifs throughout the entire transcriptome. Computational methods for discovery and analysis of sequence motifs in high-throughput mRNA expression profiling experiments are becoming increasingly important tools for the identification of post-transcriptional regulatory motifs and the inference of the regulators and their targets.
cWords is a method designed for regulatory motif discovery in differential case-control mRNA expression datasets. We have improved the algorithms and statistical methods of cWords, resulting in at least a factor 100 speed gain over the previous implementation. On a benchmark dataset of 19 microRNA (miRNA) perturbation experiments cWords showed equal or better performance than two comparable methods, miReduce and Sylamer. We have developed rigorous motif clustering and visualization that accompany the cWords analysis for more intuitive and effective data interpretation. To demonstrate the versatility of cWords we show that it can also be used for identification of potential siRNA off-target binding. Moreover, cWords analysis of an experiment profiling mRNAs bound by Argonaute ribonucleoprotein particles discovered endogenous miRNA binding motifs.
cWords is an unbiased, flexible and easy-to-use tool designed for regulatory motif discovery in differential case-control mRNA expression datasets. cWords is based on rigorous statistical methods that demonstrate comparable or better performance than other existing methods. Rich visualization of results promotes intuitive and efficient interpretation of data. cWords is available as a stand-alone Open Source program at Github https://github.com/simras/cWords and as a web-service at: http://servers.binf.ku.dk/cwords/.
The primary treatment of the common malignancy squamous cell carcinoma is surgical removal. In this process, sufficient tissue removal is balanced against unnecessary mutilation. We recently ...presented a remote photoplethysmography algorithm, which revealed significant differences between processed video recordings of cancer biopsy areas and surrounding tissue. The aim of this study was to investigate whether spatial analyses of photoplethysmography data correlate with post-excision pathological analyses and thus have potential to assist in tumour delineation. Based on high speed video recordings of 11 patients with squamous cell carcinoma, we examined different parameters derived from temporal remote photoplethysmography variations. Signal characteristics values in sites matching histological sections were compared with pathological measures. Values were ranked and statistically tested with a Kendall correlation analysis. A moderate, negative correlation was found between signal oscillations and the width and transversal area of squamous cell carcinoma in the frequencies below 1 Hz and specifically from 0.02 to 0.15 Hz. We have presented a correlation between frequency content and prevalence of cancer based on regular video recordings of squamous cell carcinoma. We believe this is supported by published findings on malignant melanoma. Our findings indicate that photoplethysmography can be used to distinguish SCC from healthy skin.
Abstract
Background
Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have ...reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.
Methods
We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-
A, B, C, DPB1, DQA1, DQB1
and
DRB1
). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.
Results
Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with “other” infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of
HLA-C
alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.
Conclusions
Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.
Colorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and ...CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection.
We conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC.
None of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5.
Individual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.
Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well ...understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned.
We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study.
Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods.
Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the ...recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment.
A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults.
The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer.
The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.
The World Health Organization has expressed concerns that some workers may be at higher risk of developing severe COVID-19 illness because of age or pre-existing medical conditions.4 Despite being a ...topic on the political agenda, in social media and patient organisations, surprisingly little is known regarding the impact of the ongoing pandemic on anxiety and concerns related to the work situation, and in a review of the medical literature, we found no previous research publications regarding patients with IRD. Demographic and clinical factors associated with work-related concerns were explored with multivariable logistic regression (mostly or completely agree vs other responses) including gender, age (<40/40–60/>60 years), diagnosis (RA/PsA/AxSpA/other), educational level (higher/lower), other comorbidities (yes/no/missing), biological DMARD (bDMARD) treatment (yes/no) and health-related QoL (EQ-5D) (below/above median). Among 14 758 respondents (38% of eligible patients), 5950 patients (40%) were working (60% full time/31% part time/9% self-employed), 61% were female, median age was 55 (IQR 47–60) years, 53% had RA/19% PsA/20% AxSpA/9% other IRD, 53% had higher educational level, 47% reported other comorbidities, 36% received bDMARDs, and self-reported EQ-5D was median 0.80 (IQR 0.74–0.86). In multivariable logistic regression analyses including respondents with complete data (n=5878), factors associated with being concerned about being in the work environment were female gender (odds ratio (OR) (95% CI) 1.96 (1.68 to 2.28)), higher educational level (1.34 (1.17 to 1.54)), other comorbidities (yes vs no, 1.37 (1.19 to 1.58)), treatment with bDMARDs (1.46 (1.27 to 1.68)) and poorer EQ-5D (2.71 (2.35 to 3.13)) (all p<0.001).
The innate immune system constitutes the first line of defense against infections and is also important for initiating the development of an adaptive immune response. The innate immune system ...recognizes microbial infection through germline-encoded pattern recognition receptors, which are responsible for decoding the microbial fingerprint and activating an appropriate response against the invading pathogen. In this review, we present and discuss current knowledge on how the innate immune system recognizes intracellular pathogens, activates intracellular signaling, induces gene expression, and orchestrates the microbicidal response against pathogens with a habitat within host cells.
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