There is no such thing as a Ministry of Truth and why it is important to challenge conventional "wisdom" - A personal view.
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ABSTRACT:
SUBMITTER: Brouqui P
PROVIDER: S-EPMC10320372 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
Publications
There is no such thing as a Ministry of Truth and why it is important to challenge conventional "wisdom" - A personal view.
Brouqui Philippe P Drancourt Michel M Raoult Didier D
New microbes and new infections 20230622
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Project description:Symbionts can substantially affect the evolution and ecology of their hosts. The investigation of the tissue-specific distribution of symbionts (tissue tropism) can provide important insight into host-symbiont interactions. Among other things, it can help to discern the importance of specific transmission routes and potential phenotypic effects. The intracellular bacterial symbiont Wolbachia has been described as the greatest ever panzootic, due to the wide array of arthropods that it infects. Being primarily vertically transmitted, it is expected that the transmission of Wolbachia would be enhanced by focusing infection in the reproductive tissues. In social insect hosts, this tropism would logically extend to reproductive rather than sterile castes, since the latter constitute a dead-end for vertically transmission. Here, we show that Wolbachia are not focused on reproductive tissues of eusocial insects, and that non-reproductive tissues of queens and workers of the ant Acromyrmex echinatior, harbour substantial infections. In particular, the comparatively high intensities of Wolbachia in the haemolymph, fat body, and faeces, suggest potential for horizontal transmission via parasitoids and the faecal-oral route, or a role for Wolbachia modulating the immune response of this host. It may be that somatic tissues and castes are not the evolutionary dead-end for Wolbachia that is commonly thought.
| S-EPMC4079706 | biostudies-literature
Project description:ObjectiveWithin the context of the Third i2b2 Workshop on Natural Language Processing Challenges for Clinical Records, the authors (also referred to as 'the i2b2 medication challenge team' or 'the i2b2 team' for short) organized a community annotation experiment.DesignFor this experiment, the authors released annotation guidelines and a small set of annotated discharge summaries. They asked the participants of the Third i2b2 Workshop to annotate 10 discharge summaries per person; each discharge summary was annotated by two annotators from two different teams, and a third annotator from a third team resolved disagreements.MeasurementsIn order to evaluate the reliability of the annotations thus produced, the authors measured community inter-annotator agreement and compared it with the inter-annotator agreement of expert annotators when both the community and the expert annotators generated ground truth based on pooled system outputs. For this purpose, the pool consisted of the three most densely populated automatic annotations of each record. The authors also compared the community inter-annotator agreement with expert inter-annotator agreement when the experts annotated raw records without using the pool. Finally, they measured the quality of the community ground truth by comparing it with the expert ground truth.Results and conclusionsThe authors found that the community annotators achieved comparable inter-annotator agreement to expert annotators, regardless of whether the experts annotated from the pool. Furthermore, the ground truth generated by the community obtained F-measures above 0.90 against the ground truth of the experts, indicating the value of the community as a source of high-quality ground truth even on intricate and domain-specific annotation tasks.
| S-EPMC2995684 | biostudies-literature
Project description:In November 1973, my colleagues A. C. Y. Chang, H. W. Boyer, R. B. Helling, and I reported in PNAS that individual genes can be cloned and isolated by enzymatically cleaving DNA molecules into fragments, linking the fragments to an autonomously replicating plasmid, and introducing the resulting recombinant DNA molecules into bacteria. A few months later, Chang and I reported that genes from unrelated bacterial species can be combined and propagated using the same approach and that interspecies recombinant DNA molecules can produce a biologically functional protein in a foreign host. Soon afterward, Boyer's laboratory and mine published our collaborative discovery that even genes from animal cells can be cloned in bacteria. These three PNAS papers quickly led to the use of DNA cloning methods in multiple areas of the biological and chemical sciences. They also resulted in a highly public controversy about the potential hazards of laboratory manipulation of genetic material, a decision by Stanford University and the University of California to seek patents on the technology that Boyer and I had invented, and the application of DNA cloning methods for commercial purposes. In the 40 years that have passed since publication of our findings, use of DNA cloning has produced insights about the workings of genes and cells in health and disease and has altered the nature of the biotechnology and biopharmaceutical industries. Here, I provide a personal perspective of the events that led to, and followed, our report of DNA cloning.
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Project description:Extracellular vesicles (EVs) are pivotal in intercellular communication, impacting diverse physiological and pathological processes. Current in vitro EV biogenesis studies often utilize pharmacological inhibitors, inducing off-target effects and overlooking cell-specific production nuances. Addressing these limitations, we utilized CRISPR/Cas9 to generate heterozygous full-body and conditional sphingomyelin phosphodiesterase 3 (Smpd3) knockout (KO) transgenic mice. Smpd3, also known as neutral sphingomyelinase 2 (nSMase2), triggers membrane curvature through sphingomyelin hydrolysis to ceramide, thereby influencing exosome release. Intriguingly, Smpd3 deficiency demonstrated no impact on EV release both in vitro and in vivo, underscoring its potential cell-type-specific role in EV biogenesis. Notably, bone marrow derived macrophages (BMDMs) did exhibit reduced EV release upon Alix deletion. Our findings open avenues for subsequent inquiries, enriching our knowledge of EV biogenesis and illuminating intercellular communication in health and disease.
| S-EPMC11544639 | biostudies-literature
Project description:BackgroundSepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis.MethodsIn the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient's condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived.ResultsWe analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the "worst" working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively.ConclusionsGTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.
| S-EPMC8760797 | biostudies-literature
Project description: Not available
| S-EPMC2864100 | biostudies-literature
Project description:The introduction of synchrotron radiation sources almost four decades ago has led to a revolutionary change in the way that diffraction data from macromolecular crystals are being collected. Here a brief history of the development of methodologies that took advantage of the availability of synchrotron sources are presented, and some personal experiences with the utilization of synchrotrons in the early days are recalled.
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Project description:ObjectivesTo explore patients' perceptions of the features of personal care and how far these are shared by healthcare providers; whether a continuing relationship between a health professional and a patient is essential for personal care; and the circumstances in which a continuing relationship is important.DesignQualitative analysis of semistructured interviews using the "framework" approach.SettingSix general practices in Leicestershire.Participants40 patients aged > or = 18 years, 13 general practitioners, 10 practice and community nurses, and six practice administrative staff, recruited through participating practices.ResultsPatients' and healthcare providers' accounts cited human communication, individualised treatment or management, and whole person care as features of personal care. Personal care was described in three different contexts-a continuing relationship, a single consultation, and from the practice as a whole. The extent to which a continuing relationship was important for personal care was determined by the reason for consulting, as well as patients' consulting history and lifestyle.ConclusionsPatients, general practitioners, primary care nurses, and administrative staff hold similar views on the meaning of personal care, despite differences of emphasis reflecting their different roles. Personal care is promoted by but not always dependent on a continuing provider-patient relationship; human communication and individualised care emerged as important in making care personal whatever the context. Most respondents valued relationships in primary care and had clear ideas about when care in the context of a relationship was most valuable.
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