Explore the vast range of titles available.

In this paper, a simple yet interpretable, probabilistic model is proposed for the prediction of reported case counts of infectious diseases. A spatio-temporal kernel is derived from training data to capture the typical interaction effects of reported infections across time and space, which provides insight into the dynamics of the spread of infectious diseases. Testing the model on a one-week-ahead prediction task for campylobacteriosis and rotavirus infections across Germany, as well as Lyme borreliosis across the federal state of Bavaria, shows that the proposed model performs on-par with the state-of-the-art hhh4 model. However, it provides a full posterior distribution over parameters in addition to model predictions, which aides in the assessment of the model. The employed Bayesian Monte Carlo regression framework is easily extensible and allows for incorporating prior domain knowledge, which makes it suitable for use on limited, yet complex datasets as often encountered in epidemiology.

Phosphoinositides are important regulators of intracellular membrane traffic, and although the role of PI(4,5)P 2 has been well characterised, the function of PI(3,4)P 2 remains unclear; here the formation of PI(3,4)P 2 by the class II phosphatidylinositol-3-kinase C2α enzyme is shown to control clathrin-mediated endocytosis. Endocytosis control by lipid switch Phosphoinositides are important regulators of intracellular membrane traffic. Although the role of phosphatidylinositol-4,5-bisphosphate has been well characterized, that of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) remains unclear. In this study, Volker Haucke and colleagues show that formation of PI(3,4)P 2 by the class II phosphatidylinositol-3-kinase C2α (PI(3)K C2α) enzyme spatiotemporally controls clathrin-mediated endocytosis. These findings present a novel function of PI(3,4)P 2 in membrane traffic. Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic 1 , 2 . Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits 3 , 4 , 5 , 6 . No phosphatidylinositol other than PI(4,5)P 2 has been implicated in clathrin-mediated endocytosis, whereas the subsequent endosomal stages of the endocytic pathway are dominated by phosphatidylinositol-3-phosphates(PI(3)P) 7 . How phosphatidylinositol conversion from PI(4,5)P 2 -positive endocytic intermediates to PI(3)P-containing endosomes is achieved is unclear. Here we show that formation of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) by class II phosphatidylinositol-3-kinase C2α (PI(3)K C2α) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P 2 or PI(3)K C2α impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P 2 by PI(3)K C2α is required for selective enrichment of the BAR domain protein SNX9 at late-stage endocytic intermediates. These findings provide a mechanistic framework for the role of PI(3,4)P 2 in endocytosis and unravel a novel discrete function of PI(3,4)P 2 in a central cell physiological process.

Clathrin-mediated endocytosis (CME) involves membrane-associated scaffolds of the bin-amphiphysin-rvs (BAR) domain protein family as well as the GTPase dynamin, and is accompanied and perhaps triggered by changes in local lipid composition. How protein recruitment, scaffold assembly and membrane deformation is spatiotemporally controlled and coupled to fission is poorly understood. We show by computational modelling and super-resolution imaging that phosphatidylinositol 3,4-bisphosphate [PI(3,4)P 2 ] synthesis within the clathrin-coated area of endocytic intermediates triggers selective recruitment of the PX-BAR domain protein SNX9, as a result of complex interactions of endocytic proteins competing for phospholipids. The specific architecture induces positioning of SNX9 at the invagination neck where its self-assembly regulates membrane constriction, thereby providing a template for dynamin fission. These data explain how lipid conversion at endocytic pits couples local membrane constriction to fission. Our work demonstrates how computational modelling and super-resolution imaging can be combined to unravel function and mechanisms of complex cellular processes. The spatiotemporal regulation of membrane scaffolds recruitment and coupling between membrane deformation and fission in endocytosis are unclear. Here the authors show that lipid conversion at endocytic pits recruits SNX9, which couples local membrane constriction to fission in endocytosis.

Background During the COVID-19 pandemic and associated public health and social measures, decreasing patient numbers have been described in various healthcare settings in Germany, including emergency care. This could be explained by changes in disease burden, e.g. due to contact restrictions, but could also be a result of changes in utilisation behaviour of the population. To better understand those dynamics, we analysed routine data from emergency departments to quantify changes in consultation numbers, age distribution, disease acuity and day and hour of the day during different phases of the COVID-19 pandemic. Methods We used interrupted time series analyses to estimate relative changes for consultation numbers of 20 emergency departments spread throughout Germany. For the pandemic period (16-03-2020 – 13-06-2021) four different phases of the COVID-19 pandemic were defined as interruption points, the pre-pandemic period (06-03-2017 – 09-03-2020) was used as the reference. Results The most pronounced decreases were visible in the first and second wave of the pandemic, with changes of − 30.0% (95%CI: − 32.2%; − 27.7%) and − 25.7% (95%CI: − 27.4%; − 23.9%) for overall consultations, respectively. The decrease was even stronger for the age group of 0–19 years, with − 39.4% in the first and − 35.0% in the second wave. Regarding acuity levels, consultations assessed as urgent, standard, and non-urgent showed the largest decrease, while the most severe cases showed the smallest decrease. Conclusions The number of emergency department consultations decreased rapidly during the COVID-19 pandemic, without extensive variation in the distribution of patient characteristics. Smallest changes were observed for the most severe consultations and older age groups, which is especially reassuring regarding concerns of possible long-term complications due to patients avoiding urgent emergency care during the pandemic.

According to the World Health Organization (WHO), around 60% of all outbreaks are detected using informal sources. In many public health institutes, including the WHO and the Robert Koch Institute (RKI), dedicated groups of public health agents sift through numerous articles and newsletters to detect relevant events. This media screening is one important part of event-based surveillance (EBS). Reading the articles, discussing their relevance, and putting key information into a database is a time-consuming process. To support EBS, but also to gain insights into what makes an article and the event it describes relevant, we developed a natural language processing framework for automated information extraction and relevance scoring. First, we scraped relevant sources for EBS as done at the RKI (WHO Disease Outbreak News and ProMED) and automatically extracted the articles’ key data: disease , country , date , and confirmed-case count . For this, we performed named entity recognition in two steps: EpiTator, an open-source epidemiological annotation tool, suggested many different possibilities for each. We extracted the key country and disease using a heuristic with good results. We trained a naive Bayes classifier to find the key date and confirmed-case count, using the RKI’s EBS database as labels which performed modestly. Then, for relevance scoring, we defined two classes to which any article might belong: The article is relevant if it is in the EBS database and irrelevant otherwise. We compared the performance of different classifiers, using bag-of-words, document and word embeddings. The best classifier, a logistic regression, achieved a sensitivity of 0.82 and an index balanced accuracy of 0.61. Finally, we integrated these functionalities into a web application called EventEpi where relevant sources are automatically analyzed and put into a database. The user can also provide any URL or text, that will be analyzed in the same way and added to the database. Each of these steps could be improved, in particular with larger labeled datasets and fine-tuning of the learning algorithms. The overall framework, however, works already well and can be used in production, promising improvements in EBS. The source code and data are publicly available under open licenses.

Daily COVID-19 data reported by WHO may provide the basis for political ad hoc decisions including travel restrictions. Data reported by countries, however, are heterogeneous and metrics to evaluate its quality are scarce. In this work, we analysed COVID-19 case counts provided by WHO and developed tools to evaluate country-specific reporting behaviours. In this retrospective cross-sectional study, COVID-19 data reported daily to WHO from 3 January 2020 until 14 June 2021 were analysed. We proposed the concepts of binary reporting rate and relative reporting behaviour and performed descriptive analyses for all countries with these metrics. We developed a score to evaluate the consistency of incidence and binary reporting rates. Further, we performed spectral clustering of the binary reporting rate and relative reporting behaviour to identify salient patterns in these metrics. Our final analysis included 222 countries and regions. Reporting scores varied between -0.17, indicating discrepancies between incidence and binary reporting rate, and 1.0 suggesting high consistency of these two metrics. Median reporting score for all countries was 0.71 (IQR 0.55-0.87). Descriptive analyses of the binary reporting rate and relative reporting behaviour showed constant reporting with a slight 'weekend effect' for most countries, while spectral clustering demonstrated that some countries had even more complex reporting patterns. The majority of countries reported COVID-19 cases when they did have cases to report. The identification of a slight 'weekend effect' suggests that COVID-19 case counts reported in the middle of the week may represent the best data basis for political ad hoc decisions. A few countries, however, showed unusual or highly irregular reporting that might require more careful interpretation. Our score system and cluster analyses might be applied by epidemiologists advising policy makers to consider country-specific reporting behaviours in political ad hoc decisions.

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges.

Particle-based reaction-diffusion algorithms facilitate the modeling of the diffusional motion of individual molecules and the reactions between them in cellular environments. A physically realistic model, depending on the system at hand and the questions asked, would require different levels of modeling detail such as particle diffusion, geometrical confinement, particle volume exclusion or particle-particle interaction potentials. Higher levels of detail usually correspond to increased number of parameters and higher computational cost. Certain systems however, require these investments to be modeled adequately. Here we present a review on the current field of particle-based reaction-diffusion software packages operating on continuous space. Four nested levels of modeling detail are identified that capture incrementing amount of detail. Their applicability to different biological questions is discussed, arching from straight diffusion simulations to sophisticated and expensive models that bridge towards coarse grained molecular dynamics.

Synaptic vesicle fusion is mediated by SNARE proteins forming in between synaptic vesicle (v-SNARE) and plasma membrane (t-SNARE), one of which is Syntaxin-1A. Although exocytosis mainly occurs at active zones, Syntaxin-1A appears to cover the entire neuronal membrane. By using STED super-resolution light microscopy and image analysis of Drosophila neuro-muscular junctions, we show that Syntaxin-1A clusters are more abundant and have an increased size at active zones. A computational particle-based model of syntaxin cluster formation and dynamics is developed. The model is parametrized to reproduce Syntaxin cluster-size distributions found by STED analysis, and successfully reproduces existing FRAP results. The model shows that the neuronal membrane is adjusted in a way to strike a balance between having most syntaxins stored in large clusters, while still keeping a mobile fraction of syntaxins free or in small clusters that can efficiently search the membrane or be traded between clusters. This balance is subtle and can be shifted toward almost no clustering and almost complete clustering by modifying the syntaxin interaction energy on the order of only 1 kBT. This capability appears to be exploited at active zones. The larger active-zone syntaxin clusters are more stable and provide regions of high docking and fusion capability, whereas the smaller clusters outside may serve as flexible reserve pool or sites of spontaneous ectopic release.

Emergency department (ED) routine data offer a unique opportunity for syndromic surveillance of communicable and noncommunicable diseases (NCDs). In 2020, the Robert Koch Institute established a syndromic surveillance system using ED data from the AKTIN registry. The system provides daily insights into ED utilization for infectious diseases. Adding NCD indicators to the surveillance is of great public health importance, especially during acute events, where timely monitoring enables targeted public health responses and communication. This study aimed to develop and validate syndrome definitions for the NCD indicators of acute coronary syndrome (ACS), myocardial infarction (MI), and stroke (STR). First, syndrome definitions were developed with clinical experts combining ED diagnosis, chief complaints, diagnostic certainty, and discharge information. Then, using the multicenter retrospective routine ED data provided by the AKTIN registry, we conducted internal validation by linking ED cases fulfilling the syndrome definition with the hospital discharge diagnoses and calculating sensitivity, specificity, and accuracy. Lastly, external validation comprised the comparison of the ED cases fulfilling the syndrome definition with the federal German hospital diagnosis statistic. Ratios comparing the relative number of cases for all syndrome definitions were calculated and stratified by age and sex. We analyzed data from 9 EDs, totaling 704,797 attendances from January 1, 2019, to March 5, 2021. Syndrome definitions were based on ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision-German Modification) diagnoses, chief complaints, and discharge information. We identified 4.3% of all cases as ACS, 0.6% as MI, and 3.2% as STR. Patients with ACS and MI were more likely to be male (58.3% and 64.7%), compared to the overall attendances (52.7%). For all syndrome definitions, the prevalence was higher in the older age groups (60-79 years and >80 years), and the highest proportions of cases were assigned an urgency level (3=urgent or 2=very urgent). The internal validation showed accuracy and specificity levels above 96% for all syndrome definitions. The sensitivity was 85.3% for ACS, 56.6% for MI, and 80.5% for STR. The external validation showed high levels of correspondence between the ED data and the German hospital statistics, with most ratios ranging around 1, indicating congruence, particularly in older age groups. The highest differences were noted in younger age groups, with the highest ratios in women aged between 20 and 39 years (4.57 for MI and 4.17 for ACS). We developed NCD indicators for ACS, MI, and STR that showed high levels of internal and external validity. The integration of these indicators into the syndromic surveillance system for EDs could enable daily monitoring of NCD patterns and trends to enhance timely public health surveillance in Germany.