Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods

Scholarly publishing depends on peer reviewers

The peer-review crisis is posing a risk to the scholarly peer-reviewed journal system. Journals have to ask many potential peer reviewers to obtain a minimum acceptable number of peers accepting reviewing a manuscript. Several solutions have been suggested to overcome this shortage. From reimbursing for the job, to eliminating pre-publication reviews, one cannot predict which is more dangerous for the future of scholarly publishing. And, why not acknowledging their contribution to the final version of the article published? PubMed created two categories of contributors: authors [AU] and collaborators [IR]. Why not a third category for the peer-reviewer?Scopu

Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell-driven rejection of high-grade glioma

The promise of dendritic cell (DC)-based immunotherapy has been established by two decades of translational research. Of the four malignancies most targeted with clinical DC immunotherapy, high-grade glioma (HGG) has shown the highest susceptibility. HGG-induced immunosuppression is a roadblock to immunotherapy, but may be overcome by the application of T helper 1 (T(H)1) immunity-biased, next-generation, DC immunotherapy. To this end, we combined DC immunotherapy with immunogenic cell death (ICD; a modality shown to induce T(H)1 immunity) induced by hypericin-based photodynamic therapy. In an orthotopic HGG mouse model involving prophylactic/curative setups, both biologically and clinically relevant versions of ICD-based DC vaccines provided strong anti-HGG survival benefit. We found that the ability of DC vaccines to elicit HGG rejection was significantly blunted if cancer cell-associated reactive oxygen species and emanating danger signals were blocked either singly or concomitantly, showing hierarchical effect on immunogenicity, or if DCs, DC-associated MyD88 signal, or the adaptive immune system (especially CD8(+) T cells) were depleted. In a curative setting, ICD-based DC vaccines synergized with standard-of-care chemotherapy (temozolomide) to increase survival of HGG-bearing mice by ~300%, resulting in ~50% long-term survivors. Additionally, DC vaccines also induced an immunostimulatory shift in the brain immune contexture from regulatory T cells to T(H)1/cytotoxic T lymphocyte/T(H)17 cells. Analysis of the The Cancer Genome Atlas glioblastoma cohort confirmed that increased intratumor prevalence of T(H)1/cytotoxic T lymphocyte/T(H)17 cells linked genetic signatures was associated with good patient prognosis. Therefore, pending final preclinical checks, ICD-based vaccines can be clinically translated for glioma treatment.status: publishe

Relationship between adherence to remote monitoring and patient characteristics: observational study in women with pregnancy-induced hypertension

BACKGROUND: Pregnancy-induced hypertension (PIH) is associated with high levels of morbidity and mortality in mothers, fetuses, and newborns. New technologies, such as remote monitoring (RM), were introduced in 2015 into the care of patients at risk of PIH in Ziekenhuis Oost-Limburg (Genk, Belgium) to improve both maternal and neonatal outcomes. In developing new strategies for obstetric care in pregnant women, including RM, it is important to understand the psychosocial characteristics associated with adherence to RM in order to optimize care. OBJECTIVE: Therefore, the aim of this study was to explore the role of patients’ psychosocial characteristics (severity of depression or anxiety, cognitive factors, attachment styles, and personality traits) in their adherence to RM. METHODS: Questionnaires were sent by email to 108 mothers the day after they entered an RM program for pregnant women at risk of PIH. The Generalized Anxiety Disorder Assessment (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety and the severity of depression, respectively; an adaptation of the Pain Catastrophizing Scale (PCS) was used to assess cognitive factors; and attachment and personality were measured with the Experiences in Close Relationships-Revised Scale (ECR-R), and the Depressive Experiences Questionnaire (DEQ–A) and the Multidimensional Perfectionism Scale (MPS), respectively. RESULTS: The moderate adherence group showed significantly higher levels of anxiety and depression, negative cognitions and insecure attachment styles, especially compared with the high adherence group. The low adherence group scored significantly higher than the other groups on other-oriented perfectionism. There were no significant differences between the good and high adherence groups. CONCLUSIONS: This study demonstrates the relationships between adherence to RM and patient characteristics in women at risk of PIH. Alertness towards the group of women who show less than optimal adherence is essential. These findings call for further research on the management of PIH and the importance of individual tailoring of RM in this patient group

Data_Sheet_1_Sleep syncope—A systematic review.pdf

BackgroundSleep syncope is a subtype of vasovagal syncope in which patients experience syncope after awakening from their sleep. The aim was to investigate the association of clinical characteristics and gastrointestinal symptoms with syncope, as well as the body position in which symptoms began.MethodsA systematic search of studies was performed in MEDLINE and EMBASE without language restrictions, from inception to 9 January 2022. Studies were included if they reported data on the proportion of patients who experienced symptoms (nausea, vomiting, abdominal pain, and diarrhea) associated with syncope.ResultsData were included for 116 patients in 13 studies. Patients were 46.9 ± 4.3 years and 61.4% were female. In 52.5% of patients, a supine body position at the time of syncope was reported. A history of phobias was reported by 67.6% of patients, and 96.5% of patients also had typical daytime vasovagal syncope. In the 5 studies reporting the results of head-up tilt testing (n = 77), 90.9% of patients had positive tests. Gastrointestinal symptoms were present in the majority of patients with reported rates of 65.6% for upper gastrointestinal symptoms and 86.0% for lower gastrointestinal symptoms.ConclusionPatients with sleep syncope patients are predominantly female with a history of daytime vasovagal syncope. Gastrointestinal symptoms are present in the majority of patients and is therefore an important feature of sleep syncope.</p

Supplementary Material for: eEduHeart I: A Multicenter, Randomized, Controlled Trial Investigating the Effectiveness of a Cardiac Web-Based eLearning Platform - Rationale and Study Design

<p><b><i>Objectives:</i></b> Cardiac telerehabilitation includes, in its most comprehensive format, telemonitoring, telecoaching, social interaction, and eLearning. The specific role of eLearning, however, was seldom assessed. The aim of eEduHeart I is to investigate the medium-term effectiveness of the addition of a cardiac web-based eLearing platform to conventional cardiac care. <b><i>Methods:</i></b> In this prospective, multicenter randomized, controlled trial, 1,000 patients with coronary artery disease will be randomized 1:1 to an intervention group (receiving 1-month unrestricted access to the cardiac eLearning platform in addition to conventional cardiac care) or to conventional cardiac care alone. The primary endpoint is health-related quality of life, assessed by the HeartQoL questionnaire at the 1- and 3-month follow-ups. Secondary endpoints include pathology-specific knowledge and self-reported eLearning platform user experience. Data on the eLearning platform usage will be gathered through web logging during the study period. <b><i>Results:</i></b> eEduHeart I will be one of the first studies to report on the added value of eLearning. <b><i>Conclusions:</i></b> If the intervention is proven effective, current cardiac telerehabilitation programs can be augmented by including eLearning, too. The platform can then be used as a model for other chronic diseases in which patient education plays a key role.</p