Focused Update on Clinical Testing of Otolith Organs.

Sensing gravity through the otolith receptors is crucial for bipedal stability and gait. The overall contribution of the otolith organs to eye movements, postural control, and perceptual functions is the basis for clinical testing of otolith function. With such a wide range of contributions, it is important to recognize that the functional outcomes of these tests may vary depending on the specific method employed to stimulate the hair cells. In this article, we review common methods used for clinical evaluation of otolith function and discuss how different aspects of physiology may affect the functional measurements in these tests. We compare the properties and performance of various clinical tests with an emphasis on the newly developed video ocular counter roll (vOCR), measurement of ocular torsion on fundus photography, and subjective visual vertical or horizontal (SVV/SVH) testing.

The role of pain and interpretation bias in fear of disease progression in people with diabetes.

Research indicates that fear of progression (FoP) may be a transdiagnostic construct underlying anxiety in people with chronic health conditions. Theories propose that interpretation of illness-related symptoms (such as pain) might be an important mechanism driving the development of FoP. However, FoP has rarely been studied in diabetes. In this study, we assessed FoP, pain, health threat-related interpretation bias, emotional states, and treatment-adherence in 198 participants with Type 1 or Type 2 diabetes and an age and gender-matched control group. We hypothesised that 1) people with diabetes will be more likely to interpret ambiguous stimuli as health threat-related than people without diabetes, 2) amongst those with diabetes, pain severity and interpretation bias will be associated with more severe levels of FoP, and 3) interpretation bias will moderate the relationship between pain severity and FoP in people with diabetes, such that the positive association between pain and FoP will become stronger when people have greater interpretation bias. Our results confirmed that people with diabetes were more likely to interpret ambiguous information as health threat-related compared to people without diabetes, with a large effect (d=0.84). Moreover, people with diabetes who reported persistent pain were more likely to interpret ambiguous stimuli as health threat-related (d=0.49). Amongst people with diabetes, pain severity and interpretation bias were significantly associated with FoP. However, we did not find evidence that interpretation bias moderated the relationship between pain and FoP and these relationships could not be accounted for by general psychopathology. PERSPECTIVE: People with diabetes had greater health threat-related interpretation bias than people without diabetes, especially for those with persistent pain and more severe fear of progression (FoP). Both pain severity and interpretation bias were associated with greater FoP, but interpretation bias did not moderate the relationship between pain and FoP.

Tissue-specific and endogenous protein labeling with split fluorescent proteins.

The ability to label proteins by fusion with genetically encoded fluorescent proteins is a powerful tool for understanding dynamic biological processes. However, current approaches for expressing fluorescent protein fusions possess drawbacks, especially at the whole organism level. Expression by transgenesis risks potential overexpression artifacts while fluorescent protein insertion at endogenous loci is technically difficult and, more importantly, does not allow for tissue-specific study of broadly expressed proteins. To overcome these limitations, we have adopted the split fluorescent protein system mNeonGreen21-10/11 (split-mNG2) to achieve tissue-specific and endogenous protein labeling in zebrafish. In our approach, mNG21-10 is expressed under a tissue-specific promoter using standard transgenesis while mNG211 is inserted into protein-coding genes of interest using CRISPR/Cas-directed gene editing. Each mNG2 fragment on its own is not fluorescent, but when co-expressed the fragments self-assemble into a fluorescent complex. Here, we report successful use of split-mNG2 to achieve differential labeling of the cytoskeleton genes tubb4b and krt8 in various tissues. We also demonstrate that by anchoring the mNG21-10 component to specific cellular compartments, the split-mNG2 system can be used to manipulate protein localization. Our approach should be broadly useful for a wide range of applications.

Single-cell and spatial transcriptomics analysis of non-small cell lung cancer.

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional "reprogramming" of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

Functionalization of Supramolecular Polymers by Dynamic Covalent Boroxine Chemistry.

Molecular scaffolds that enable the combinatorial synthesis of new supramolecular building blocks are promising targets for the construction of functional molecular systems. Here, we report a supramolecular scaffold based on boroxine that enables the formation of chiral and ordered 1D supramolecular polymers, which can be easily functionalized for circularly polarized luminescence. The boroxine monomers are quantitatively synthesized in situ, both in bulk and in solution, from boronic acid precursors and cooperatively polymerize into 1D helical aggregates stabilized by threefold hydrogen-bonding and π-π stacking. We then demonstrate amplification of asymmetry in the co-assembly of chiral/achiral monomers and the co-condensation of chiral/achiral precursors in classical and in situ sergeant-and-soldiers experiments, respectively, showing fast boronic acid exchange reactions occurring in the system. Remarkably, co-condensation of pyrene boronic acid with a hydrogen-bonding chiral boronic acid results in chiral pyrene aggregation with circularly polarized excimer emission and g-values in the order of 10-3. Yet, the electron deficiency of boron in boroxine makes them chemically addressable by nucleophiles, but also sensitive to hydrolysis. With this sensitivity in mind, we provide first insights into the prospects offered by boroxine-based supramolecular polymers to make chemically addressable, functional, and adaptive systems.

Elastic films of single-crystal two-dimensional covalent organic frameworks.

The properties of polycrystalline materials are often dominated by defects; two-dimensional (2D) crystals can even be divided and disrupted by a line defect1-3. However, 2D crystals are often required to be processed into films, which are inevitably polycrystalline and contain numerous grain boundaries, and therefore are brittle and fragile, hindering application in flexible electronics, optoelectronics and separation1-4. Moreover, similar to glass, wood and plastics, they suffer from trade-off effects between mechanical strength and toughness5,6. Here we report a method to produce highly strong, tough and elastic films of an emerging class of 2D crystals: 2D covalent organic frameworks (COFs) composed of single-crystal domains connected by an interwoven grain boundary on water surface using an aliphatic bi-amine as a sacrificial go-between. Films of two 2D COFs have been demonstrated, which show Young's moduli and breaking strengths of 56.7 ± 7.4 GPa and 73.4 ± 11.6 GPa, and 82.2 ± 9.1 N m-1 and 29.5 ± 7.2 N m-1, respectively. We predict that the sacrificial go-between guided synthesis method and the interwoven grain boundary will inspire grain boundary engineering of various polycrystalline materials, endowing them with new properties, enhancing their current applications and paving the way for new applications.

AmplificationTimeR: an R package for timing sequential amplification events.

MOTIVATION: Few methods exist for timing individual amplification events in regions of focal amplification. Current methods are also limited in the copy number states that they are able to time. Here we introduce AmplificationTimeR, a method for timing higher level copy number gains and inferring the most parsimonious order of events for regions that have undergone both single gains and whole genome duplication. Our method is an extension of established approaches for timing genomic gains. RESULTS: We can time more copy number states, and in states covered by other methods our results are comparable to previously published methods. AVAILABILITY AND IMPLEMENTATION: AmplificationTimer is freely available as an R package hosted at https://github.com/Wedge-lab/AmplificationTimeR.

Genomic evolution shapes prostate cancer disease type.

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.

Tissue-specific and endogenous protein labeling with split fluorescent proteins.

The ability to label proteins by fusion with genetically encoded fluorescent proteins is a powerful tool for understanding dynamic biological processes. However, current approaches for expressing fluorescent protein fusions possess drawbacks, especially at the whole organism level. Expression by transgenesis risks potential overexpression artifacts while fluorescent protein insertion at endogenous loci is technically difficult and, more importantly, does not allow for tissue-specific study of broadly expressed proteins. To overcome these limitations, we have adopted the split fluorescent protein system mNeonGreen21-10/11 (split-mNG2) to achieve tissue-specific and endogenous protein labeling in zebrafish. In our approach, mNG21-10 is expressed under a tissue-specific promoter using standard transgenesis while mNG211 is inserted into protein-coding genes of interest using CRISPR/Cas-directed gene editing. Each mNG2 fragment on its own is not fluorescent, but when co-expressed the fragments self-assemble into a fluorescent complex. Here, we report successful use of split-mNG2 to achieve differential labeling of the cytoskeleton genes tubb4b and krt8 in various tissues. We also demonstrate that by anchoring the mNG21-10 component to specific cellular compartments, the split-mNG2 system can be used to manipulate protein function. Our approach should be broadly useful for a wide range of applications.

Giant Blue Energy Harvesting in Two-Dimensional Polymer Membranes with Spatially Aligned Charges.

Blue energy between seawater and river water is attracting increasing interest, as one of the sustainable and renewable energy resources that can be harvested from water. Within the reverse electrodialysis applied in blue energy conversion, novel membranes with nanoscale confinement that function as selective ion transport mediums are currently in high demand for realizing higher power density. The primary challenge lies in constructing well-defined nanochannels that allow for low-energy barrier transport. This work proposes a concept for nanofluidic channels with a simultaneous dual electrostatic effect that can enhance both ion selectivity and flux. To actualize this, this work has synthesized propidium iodide-based two-dimensional polymer (PI-2DP) membranes possessing both skeleton charge and intrinsic space charge, which are spatially aligned along the ion transport pathway. The dual charge design of PI-2DP significantly enhances the electrostatic interaction between the translocating anions and the cationic polymer framework, and a high anion selectivity coefficient (≈0.8) is reached. When mixing standard artificial seawater and river water, this work achieves a considerable power density of 48.4 W m-2, outperforming most state-of-the-art nanofluidic membranes. Moreover, when applied between the Mediterranean Sea and the Elbe River, an output power density of 42.2 W m-2 is achieved by the PI-2DP. This nanofluidic membrane design with dual-layer charges will inspire more innovative development of ion-selective channels for blue energy conversion that will contribute to global energy consumption.

A Cu3BHT-Graphene van der Waals Heterostructure with Strong Interlayer Coupling for Highly Efficient Photoinduced Charge Separation.

Two-dimensional van der Waals heterostructures (2D vdWhs) are of significant interest due to their intriguing physical properties critically defined by the constituent monolayers and their interlayer coupling. Synthetic access to 2D vdWhs based on chemically tunable monolayer organic 2D materials remains challenging. Herein, the fabrication of a novel organic-inorganic bilayer vdWh by combining π-conjugated 2D coordination polymer (2DCP, i.e., Cu3BHT, BHT = benzenehexathiol) with graphene is reported. Monolayer Cu3BHT with detectable µm2-scale uniformity and atomic flatness is synthesized using on-water surface chemistry. A combination of diffraction and imaging techniques enables the determination of the crystal structure of monolayer Cu3BHT with atomic precision. Leveraging the strong interlayer coupling, Cu3BHT-graphene vdWh exhibits highly efficient photoinduced interlayer charge separation with a net electron transfer efficiency of up to 34% from Cu3BHT to graphene, superior to those of reported bilayer 2D vdWhs and molecular-graphene vdWhs. This study unveils the potential for developing novel 2DCP-based vdWhs with intriguing physical properties.

Stimuli-Responsive Nanostructured Viologen-Siloxane Materials for Controllable Conductivity.

Spontaneous phase separation is a promising strategy for the development of novel electronic materials, as the resulting well-defined morphologies generally exhibit enhanced conductivity. Making these structures adaptive to external stimuli is challenging, yet crucial as multistate reconfigurable switching is essential for neuromorphic materials. Here, a modular and scalable approach is presented to obtain switchable phase-separated viologen-siloxane nanostructures with sub-5 nm features. The domain spacing, morphology, and conductivity of these materials can be tuned by ion exchange, repeated pulsed photoirradiation and electric stimulation. Counterion exchange triggers a postsynthetic modification in domain spacing of up to 10%. Additionally, in some cases, 2D to 1D order-order transitions are observed with the latter exhibiting a sevenfold decrease in conductivity with respect to their 2D lamellar counterparts. Moreover, the combination of the viologen core with tetraphenylborate counterions enables reversible and in situ reduction upon light irradiation. This light-driven reduction provides access to a continuum of conducting states, reminiscent of long-term potentiation. The repeated voltage sweeps improve the nanostructures alignment, leading to increased conductivity in a learning effect. Overall, these results highlight the adaptivity of phase-separated nanostructures for the next generation of organic electronics, with exciting applications in smart sensors and neuromorphic devices.

On-Water Surface Synthesis of Vinylene-Linked Cationic Two-Dimensional Polymer Films as the Anion-Selective Electrode Coating.

Vinylene-linked two-dimensional polymers (V-2DPs) and their layer-stacked covalent organic frameworks (V-2D COFs) featuring high in-plane π-conjugation and robust frameworks have emerged as promising candidates for energy-related applications. However, current synthetic approaches are restricted to producing V-2D COF powders that lack processability, impeding their integration into devices, particularly within membrane technologies reliant upon thin films. Herein, we report the novel on-water surface synthesis of vinylene-linked cationic 2DPs films (V-C2DP-1 and V-C2DP-2) via Knoevenagel polycondensation, which serve as the anion-selective electrode coating for highly-reversible and durable zinc-based dual-ion batteries (ZDIBs). Model reactions and theoretical modeling revealed the enhanced reactivity and reversibility of the Knoevenagel reaction on the water surface. On this basis, we demonstrated the on-water surface 2D polycondensation towards V-C2DPs films that show large lateral size, tunable thickness, and high chemical stability. Representatively, V-C2DP-1 presents as a fully crystalline and face-on oriented film with in-plane lattice parameters of a=b≈43.3 Å. Profiting from its well-defined cationic sites, oriented 1D channels, and stable frameworks, V-C2DP-1 film possesses superior bis(trifluoromethanesulfonyl)imide anion (TFSI-)-transport selectivity (transference, t_=0.85) for graphite cathode in high-voltage ZDIBs, thus triggering additional TFSI--intercalation stage and promoting its specific capacity (from ~83 to 124 mAh g-1) and cycling life (>1000 cycles, 95 % capacity retention).

Thermal modeling of electrically-pumped continuous-wave microring resonator-based topological insulator lasers.

Deleterious effects caused by Joule heating in electrically-pumped continuous-wave InP-based topological insulator lasers based on two-dimensional microring resonator arrays are estimated in this theoretical study. Steady-state temperature distributions within such an array are developed using a full numerical solution. Thermal interactions between active gain regions and ring resonators pose significant operational and integration challenges, as these devices are extremely sensitive to temperature-induced changes in a material's index of refraction. Designing such an array benefits from clear understanding on the effects of systematic non-uniform heating profiles due to temperature variations among the rings. This paper first presents the thermal modeling of a single isolated ring under electrical pumping and then discusses its impact on an operational array composed of 10 × 10 such rings. The simulation results reported here were benchmarked against experimental measurements of the mircoring lasers, wherever possible. Calculations based on a tight-binding model for the array suggest that the laser exhibits single-mode optical output with the preservation of topological properties up to 4 times the threshold current. The useful operating range of the array is mainly limited by the thermal shifts of wavelengths in addition to the wavelength disorders due to fabrication imperfections.

Targeted rainfall enhancement as an objective of forestation.

Forestation efforts are accelerating across the globe in the fight against global climate change, in order to restore biodiversity, and to improve local livelihoods. Yet, so far the non-local effects of forestation on rainfall have largely remained a blind spot. Here we build upon emerging work to propose that targeted rainfall enhancement may also be considered in the prioritization of forestation. We show that the tools to achieve this are rapidly becoming available, but we also identify drawbacks and discuss which further developments are still needed to realize robust assessments of the rainfall effects of forestation in the face of climate change. Forestation programs may then mitigate not only global climate change itself but also its adverse effects in the form of drying.

Influence of chemical interactions on the electronic properties of BiOI/organic semiconductor heterojunctions for application in solution-processed electronics.

Bismuth oxide iodide (BiOI) has been viewed as a suitable environmentally-friendly alternative to lead-halide perovskites for low-cost (opto-)electronic applications such as photodetectors, phototransistors and sensors. To enable its incorporation in these devices in a convenient, scalable, and economical way, BiOI thin films were investigated as part of heterojunctions with various p-type organic semiconductors (OSCs) and tested in a field-effect transistor (FET) configuration. The hybrid heterojunctions, which combine the respective functionalities of BiOI and the OSCs were processed from solution under ambient atmosphere. The characteristics of each of these hybrid systems were correlated with the physical and chemical properties of the respective materials using a concept based on heteropolar chemical interactions at the interface. Systems suitable for application in lateral transport devices were identified and it was demonstrated how materials in the hybrids interact to provide improved and synergistic properties. These indentified heterojunction FETs are a first instance of successful incorporation of solution-processed BiOI thin films in a three-terminal device. They show a significant threshold voltage shift and retained carrier mobility compared to pristine OSC devices and open up possibilities for future optoelectronic applications.

Potential Application of Organic Electronics in Electrical Sensing of Insects and Integrated Pest Management towards Developing Ecofriendly Replacements for Chemical Insecticides.

Synthetic insecticides are widely used against plant pest insects to protect the crops. However, many insecticides have poor selectivity and are toxic also to beneficial insects, animals, and humans. In addition, insecticide residues can remain on fruits for many days, jeopardizing food safety. For these reasons, a reusable, low-cost electronic trap that can attract, detect, and identify, but attack only the pest while leaving beneficial insects unharmed could provide a sustainable, nature-friendly replacement. Here, for the first time, research results are presented suggesting the great potential and compatibility of organic electronic devices and technologies with pest management. Electrical characterizations confirm that an insect's body has relatively high dielectric permittivity. Adaptive memcapacitor circuits can track the impedance change for insect detection. Other experiments show that printed polymer piezoelectric transducers on a plastic substrate can collect information about the weight and activity of insects for identification. The breakdown voltage of most insects´ integument is measured to be <200 V. Long channel organic transistors easily work at such high voltages while being safe to touch for humans thanks to their inherent low current. This feasibility study paves the way for the future development of organic electronics for physical pest control and biodiversity protection.

Tailoring the Morphology of a Diketopyrrolopyrrole-based Polymer as Films or Wires for High-Performance OFETs using Solution Shearing.

Conjugated polymers often show efficient charge carrier transport along their backbone which is a primary factor in the electrical behavior of Organic Field Effect Transistor (OFETs) devices fabricated from these materials. Herein, a solution shearing procedure is reported to fabricate micro/nano wires from a diketopyrrolopyrrole (DPP)-based polymer. Millimeter to nanometer long polymer wires orientated in the coating direction are developed after a thorough analysis of the deposition conditions. It shows several morphological regimes-film, transition, and wires and experimentally derive a phase diagram for the parameters coating speed and surface energy of the substrate. The as-fabricated wires are isolated, which is confirmed by optical, atomic force, and scanning electron microscopy. Beside the macroscopic alignment of wires, cross-polarized optical microscopy images show strong birefringence suggesting a high degree of molecular orientation. This is further substantiated by polarized UV-Vis-NIR spectroscopy, selected area electron diffraction transmission electron microscopy, and grazing-incidence wide-angle X-ray scattering. Finally, an enhanced electrical performance of single wire OFETs is observed with a 15-fold increase in effective charge carrier mobility to 1.57 cm2 V-1 s-1 over devices using films (0.1 cm2 V-1 s-1 ) with similar values for on/off current ratio and threshold voltage.

Using within-person change in three large panel studies to estimate personality age trajectories.

How does personality change when people get older? Numerous studies have investigated this question, overall supporting the idea of so-called personality maturation. However, heterogeneous findings have left open questions, such as whether maturation continues in old age and how large the effects are. We suggest that the heterogeneity is partly rooted in methodological issues. First, studies may have failed to recover age effects as they did not stringently separate within-person changes from confounding between-person differences. Second, items supposedly belonging to the same trait may show different individual trajectories, thus rendering results sensitive to the specific set of items used. We analyzed panel data from Australia (N = 15,268; Study 1), Germany (N = 22,833; Study 2), and the Netherlands (N = 10,163; Study 3) to investigate age trends in the Big Five on the levels of both scores and items. We applied a fixed effects approach that incorporates only within-person changes over time. Developmental trends in the Big Five scores were generally moderate to large and broadly confirmed personality maturation at younger ages. At older ages, maturation consistently continued for Neuroticism, whereas we found mixed evidence for such changes in Conscientiousness and Agreeableness. Furthermore, in each study, individual items showed age trends that diverged from the rest of the corresponding trait, and these differential patterns could be partly replicated across the three studies. Our results highlight the importance of items in the study of personality development and provide an explanation for previously unaccounted for variability in age trends. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

[Urinary diversion with or without simple cystectomy as a salvage option for benign diseases of the lower urinary tract]. / Harnableitungen mit oder ohne simple Zystektomie in der Salvage-Therapie benigner Erkrankungen des unteren Harntraktes.

Benign diseases of the lower urinary tract can occur as a result of oncological or neurological diseases or their respective therapies (e.g., surgery or radiation treatment) and can significantly reduce the quality of life for affected patients. Urinary diversion serves as a salvage option when all other therapeutic regimens have been carried out and proven unsuccessful. When selecting the suitable urinary diversion, a comprehensive clinical assessment of the patients is required in order to ensure long-term success. In some cases, a cutaneous, catheterizable pouch offers the last and only option for a long-term and definitive treatment of a patient's condition. Overall, a decreasing trend in the establishment of a continent urinary diversion is observed in Germany. Current data on benign indications for urinary diversion are limited. Therefore, further data collection and research are needed.