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Background: The COVID-19 pandemic has led to a flood of—often contradictory—evidence. HCWs had to develop strategies to locate information that supported their work. We investigated the information-seeking of different HCW groups in Germany. Methods: In December 2020, we conducted online surveys on COVID-19 information sources, strategies, assigned trustworthiness, and barriers—and in February 2021, on COVID-19 vaccination information sources. Results were analyzed descriptively; group comparisons were performed using χ2-tests. Results: For general COVID-19-related medical information (413 participants), non-physicians most often selected official websites (57%), TV (57%), and e-mail/newsletters (46%) as preferred information sources—physicians chose official websites (63%), e-mail/newsletters (56%), and professional journals (55%). Non-physician HCWs used Facebook/YouTube more frequently. The main barriers were insufficient time and access issues. Non-physicians chose abstracts (66%), videos (45%), and webinars (40%) as preferred information strategy; physicians: overviews with algorithms (66%), abstracts (62%), webinars (48%). Information seeking on COVID-19 vaccination (2700 participants) was quite similar, however, with newspapers being more often used by non-physicians (63%) vs. physician HCWs (70%). Conclusion: Non-physician HCWs more often consulted public information sources. Employers/institutions should ensure the supply of professional, targeted COVID-19 information for different HCW groups.

A large fraction of monogenic disorders causes craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this “supervised” approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 17,560 patients with 1,115 rare disorders to define a “Clinical Face Phenotype Space”. Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism, as well as enable the delineation of novel phenotypes.

Abstract. Staggered and linear multi-particle trains constitute characteristic structures in inertial microfluidics. Using lattice-Boltzmann simulations, we investigate their properties and stability, when flowing through microfluidic channels. We confirm the stability of cross-streamline pairs by showing how they contract or expand to their equilibrium axial distance. In contrast, same-streamline pairs quickly expand to a characteristic separation but even at long times slowly drift apart. We reproduce the distribution of particle distances with its characteristic peak as measured in experiments. Staggered multi-particle trains initialized with an axial particle spacing larger than the equilibrium distance contract non-uniformly due to collective drag reduction. Linear particle trains, similar to pairs, rapidly expand toward a value about twice the equilibrium distance of staggered trains and then very slowly drift apart non-uniformly. Again, we reproduce the statistics of particle distances and the characteristic peak observed in experiments. Finally, we thoroughly analyze the damped displacement pulse traveling as a microfluidic phonon through a staggered train and show how a defect strongly damps its propagation. Graphical abstract

Schmidt et al. propose a new concept for colon cancer therapy that advocates specific and simultaneous targeting of different tumor cell subpopulations with high NOTCH- and MAPK-signaling pathway activity. This overcomes treatment resistance by tumor cell plasticity and strongly improves therapy response., In colorectal cancer, signaling pathways driving tumor progression are promising targets for systemic therapy. Besides WNT and MAPK signaling, activation of NOTCH signaling is found in most tumors. Here, we demonstrate that high NOTCH activity marks a distinct colon cancer cell subpopulation with low levels of WNT and MAPK activity and with a pronounced epithelial phenotype. Therapeutic targeting of MAPK signaling had limited effects on tumor growth and caused expansion of tumor cells with high NOTCH activity, whereas upon targeting NOTCH signaling, tumor cells with high MAPK activity prevailed. Lineage-tracing experiments indicated high plasticity between both tumor cell subpopulations as a mechanism for treatment resistance. Combined targeting of NOTCH and MAPK had superior therapeutic effects on colon cancer growth in vivo. These data demonstrate that tumor cells may evade systemic therapy through tumor cell plasticity and provide a new rationale for simultaneous targeting of different colon cancer cell subpopulations.

Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.

A flowing pair of particles in inertial microfluidics gives important insights into understanding and controlling the collective dynamics of particles like cells or droplets in microfluidic devices. They are applied in medical cell analysis and engineering. We study the dynamics of a pair of solid particles flowing through a rectangular microchannel using lattice Boltzmann simulations. We determine the inertial lift force profiles as a function of the two particle positions, their axial distance, and the Reynolds number. Generally, the profiles strongly differ between particles leading and lagging in flow and the lift forces are enhanced due to the presence of a second particle. At small axial distances, they are determined by viscous forces, while inertial forces dominate at large separations. We identify cross-streamline pairs as stable fixed points in the lift force profiles and argue that same-streamline configurations are only one-sided stable. Depending on the initial conditions, the two-particle lift forces in combination with the Poiseuille flow give rise to three types of unbound particle trajectories, called moving-apart, passing, and swapping, and one type of bound trajectory, where the particles perform damped oscillations towards the cross-stream line configuration. The damping rate scales with Reynolds number squared, since inertial forces are responsible for driving the particles to their steady-state positions.

We report the onset of elastic turbulence in a two-dimensional Taylor-Couette geometry using numerical solutions of the Oldroyd-B model generated with the program OpenFOAM®. Beyond a critical Weissenberg number, an elastic instability causes a supercritical transition from the laminar Taylor-Couette flow to a turbulent flow. The order parameter, the time average of secondary-flow strength, follows the scaling law with and . Additionally, the flow resistance increases beyond Wi c . The temporal power spectra of the velocity fluctuations show a power-law decay with a characteristic exponent in the range , which strongly depends on the radial position. The characteristic exponent β for the spatial power spectra obeys the necessary condition , associated with elastic turbulence, for all .

This corrects the article DOI: 10.1038/gim.2016.18.

The mechanical deformability of single cells is an important indicator for various diseases such as cancer, blood diseases and inflammation. Lab-on-a-chip devices allow to separate such cells from healthy cells using hydrodynamic forces. We perform hydrodynamic simulations based on the lattice-Boltzmann method and study the behavior of an elastic capsule in a microfluidic channel flow in the inertial regime. While inertial lift forces drive the capsule away from the channel center, its deformability favors migration in the opposite direction. Balancing both migration mechanisms, a deformable capsule assembles at a specific equilibrium distance depending on its size and deformability. We find that this equilibrium distance is nearly independent of the channel Reynolds number and falls on a single master curve when plotted versus the Laplace number. We identify a similar master curve for varying particle radius. In contrast, the actual deformation of a capsule strongly depends on the Reynolds number. The lift-force profiles behave in a similar manner as those for rigid particles. Using the Saffman effect, the capsule's equilibrium position can be controlled by an external force along the channel axis. While rigid particles move to the center when slowed down, very soft capsules show the opposite behavior. Interestingly, for a specific control force particles are focused on the same equilibrium position independent of their deformability.

Zusammenfassung Die Weiterbildung in der Klinischen Chemie und Laboratoriumsmedizin ist in Europa heterogen. Mediziner, Naturwissenschaftler und Pharmazeuten können sich in Europa in der Klinischen Chemie und Laboratoriumsmedizin weiterbilden. Die Weiterbildungszeiten und -inhalte sowie Abschlussmodalitäten unterscheiden sich jedoch voneinander. Mit dem Ziel der Harmonisierung und Qualitätssicherung der Weiterbildung in Europa veröffentlichten sowohl die Sektion „Laboratory Medicine/Medical Biopathology“ der „European Union of Medical Specialists“ (UEMS) als auch die „European Federation of Clinical Chemistry and Laboratory Medicine“ (EFLM) 2012 ein überarbeitetes Curriculum für die postgraduale Weiterbildung in der Klinischen Chemie und Laboratoriumsmedizin. Die EFLM führte die Berufsbezeichnung „Specialist in Laboratory Medicine“ (ehemals „European Specialist in Clinical Chemistry and Laboratory Medicine“) ein. Die UEMS vergibt den polyvalenten Titel „Specialist in General Laboratory Medicine – Polyvalent Medical Biopathology“ sowie 4 monovalente Titel. Die vorliegende Arbeit gibt eine Übersicht zum aktuellen Stand der Weiterbildung in der Klinischen Chemie und Laboratoriumsmedizin in den EU-Staaten im Vergleich zu Deutschland. Die Ziele der UEMS und EFLM als Dachorganisationen der Klinischen Chemie und Laboratoriumsmedizin in der EU werden diskutiert.

Autism spectrum disorder is a clinically heterogeneous condition, characterized by social deficits, language impairment, repetitive behaviors, and restricted interest. Autism displays significant genetic heterogeneity. In the past one and a half decades, next generation sequencing has enabled identification of many variants that predispose to autism. These discoveries have improved understanding of the disease etiology of autism spectrum disorder. In this review article, we will address how development of next generation sequencing has helped answer the following questions: 1. What are the modes of transmission/inheritance of autism? 2. What is the nature of genetic mutations that contribute to autism? 3. Why is there a higher prevalence of autism in males than females?

In einem Zeitalter, in dem Megabyte an Daten innerhalb weniger Sekunden uber den ganzen Globus geschickt werden konnen und sogenannte 3D-Drucker es praktisch jedermann ermoglichen, beliebige Bauteile mit geringem Aufwand nachzufertigen, wird der Schutz des Geistigen Eigentums (engl. Intellectual Property, kurz IP) immer schwieriger. Das Knowhow uber moglichst effektive Fertigungsprozesse sowie die Innovationsfahigkeit der Ingenieurinnen und Ingenieure bei der Entwicklung neuer Losungen sind jedoch Schlusselfaktoren zum Erfolg jeder Wirtschaft.

We calculate the local dielectric function ɛ(r) inside the hydration layer around a spherical solute (i) from molecular dynamics simulations including explicit solutes and (ii) theoretically using the nonlocal dielectric function of bulk water which includes the radial electric field, but not the explicit solute. The observed agreement between the two concepts shows that while ɛ(r) is strongly different from bulk, this difference is not due to restructuring of the hydrogen bond network but is mostly a consequence of the field geometry. The dielectric response differs for anions and cations, yielding a natural explanation for the well-known charge asymmetry of ionic solvation in agreement with experimental data.

We use molecular dynamics simulations to compute the spatially resolved static dielectric constant of water in cylindrical and spherical nanopores as occurring, e.g., in protein water pockets or carbon nanotubes. For this, we derive a linear-response formalism which correctly takes into account the dielectric boundary conditions in the considered geometries. We find that in cylindrical confinement, the axial component behaves similar as the local density akin to what is known near planar interfaces. The radial dielectric constant shows some oscillatory features when approaching the surface if their radius is larger than about 2 nm. Most importantly, however, the radial component exhibits pronounced oscillations at the center of the cavity. These surprising features are traced back quantitatively to the non-local dielectric nature of bulk water.