Structural Requirements for the Outpatient Treatment of Benign Diseases of the Uterus.

In many cases, outpatient surgical treatment of benign diseases of the uterus has advantages over inpatient care. This has been demonstrated by the healthcare situation in other countries. However, the prerequisite for the provision of outpatient services is that this does not lead to any impairment in the quality of care or of patient safety. The ultimate goal should not be to reduce costs but rather to maintain and, ideally, improve the quality of care. This requires that services are not just defined by the surgical procedure but also by the entire treatment chain, including, for example, psychosocial support, and are remunerated accordingly. It is particularly worrying that the final decision as to whether an outpatient operation is possible is not the responsibility of the operating unit, but of the "Medizinischer Dienst," with the corresponding options and threats of sanctions. This situation is unique internationally and requires a paradigm shift. Furthermore, structural prerequisites must be maintained which currently only exist inadequately in Germany. Since a substantial proportion of planned outpatient operations require immediate or secondary inpatient treatment, there must be a barrier-free transition between the outpatient and inpatient sectors. This will require the creation of networks between outpatient service providers and one or more hospitals that are equipped and competent to manage even complex complications. It is important to create structures that, with intensive involvement of the operating unit, include adequate preoperative evaluation and patient education as well as needs-oriented postoperative care at home. The current separation of sectors is a significant hinderance. Moreover, when expanding and promoting outpatient surgery, the aspect of training and further education of specialist staff must be taken into account, as well as cross-sectoral quality assurance. Based on a review of the international literature, this article presents 13 recommendations for adequate structures when providing outpatient services which should serve as a prerequisite for the greatest possible guarantee of patient safety.

A concept of controlling Grover diffusion operator: a new approach to solve arbitrary Boolean-based problems.

A controlled-diffusion operator for Boolean oracles is designed as a new approach for Grover's algorithm to search for solutions for arbitrary logical structures of such oracles, since the Grover diffusion operator is not able to find correct solutions for some logical structures of Boolean oracles. We also show that the Phase oracles do not work sometimes correctly using the Grover diffusion operator. Our proposed controlled-diffusion operator relies on the states of output qubit, as the reflection of Boolean decisions from a Boolean oracle without relying on the phase kickback. We prove that on many examples of Boolean and Phase oracles the Grover diffusion operator is not working correctly. The oracles in these examples are constructed using different structures of POS, SOP, ESOP, CSP-SAT, and XOR-SAT. Our mathematical models and experiments prove that the proposed controlled-diffusion operator successfully searches for all solutions for all Boolean oracles regardless of their different logical structures.

Renal-Clearable Organic Probes From D-A-D Type Aza-BODIPY Fluorophores for Multiphoton Deep-Brain Imaging.

Bright near-infrared (NIR) fluorescent probes play an important role in in vivo optical imaging. Here, renal-clearable nanodots prepared from Aza-BODIPY are reported fluorophores for multiphoton brain imaging. The design of donor-acceptor-donor (D-A-D) type conjugated structures endowed the fluorophores with large three-photon absorption cross-section for both 1620 and 2200 nm excitation. The side chain modification and lipid encapsulation yield ultrasmall nanodots (≈4 nm) and a high fluorescence quantum yield (≈0.35) at 720 nm emission in the aqueous phase. The measured three-photon action cross-section of a single Aza-BODIPY fluorophore in the nanodots is ≈30 times higher than the commonly used Sulforhodamine 101 dye. Three-photon deep brain imaging of subcortical structures is demonstrated, reaching a depth of 1900 µm below the brain surface in a live mouse study. The nanodots enabled blood flow measurement at a depth of 1617 µm using line scanning three-photon microscopy (3PM). This work provides superior fluorescent probes for multiphoton deep-brain imaging.

Fluxional halogen bonds in linear complexes of tetrafluorodiiodobenzene with dinitrobenzene.

The fluxional nature of halogen bonds (XBs) in small molecular clusters, supramolecules, and molecular crystals has received considerable attention in recent years. In this work, based on extensive density-functional theory calculations and detailed electrostatic potential (ESP), natural bonding orbital (NBO), non-covalent interactions-reduced density gradient (NCI-RDG), and quantum theory of atoms in molecules (QTAIM) analyses, we unveil the existence of fluxional halogen bonds (FXBs) in a series of linear (IC6F4I)m(OONC6H4NOO)n (m + n = 2-5) complexes of tetrafluorodiiodobenzene with dinitrobenzene which appear to be similar to the previously reported fluxional hydrogen bonds (FHBs) in small water clusters (H2O)n (n = 2-6). The obtained GS ⇌ TS ⇌ GS ' $$ \mathrm{GS}\rightleftharpoons \mathrm{TS}\rightleftharpoons {\mathrm{GS}}^{\hbox{'}} $$ fluxional mechanisms involve one FXB in the systems which fluctuates reversibly between two linear CI···O XBs in the ground states (GS and GS') via a bifurcated CI O2N van der Waals interaction in the transition state (TS). The cohesive energies (Ecoh) of these complexes with up to four XBs exhibit an almost perfect linear relationship with the numbers of XBs in the systems, with the average calculated halogen bond energy of Ecoh/XB = 3.48 kcal·mol-1 in the ground states which appears to be about 55% of the average calculated hydrogen bond energy (Ecoh/HB = 6.28 kcal·mol-1) in small water clusters.

Chemistry/structural biology of psychedelic drugs and their receptor(s).

This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.

Tertiary lymphoid structure formation: A matter of tumor-immune co-evolution.

The immune make-up of human tumors is dynamic over the course of cancer progression. However, what factors drive spatiotemporal changes in the tumor-immune landscape is not well-known. In issue 3 of Cell Reports Medicine, Liu, You, Lan and Ren et al. demonstrate that the development of tertiary lymphoid structures (TLSs) is a stepwise process that co-occurs with tumor progression in patients with lung adenocarcinoma (LUAD).

Helmets with lattice liners can mitigate traumatic brain injury from impacts.

This study explores the effectiveness of architected lattice structures, specifically made of polyamide 12 (PA12) material, as potential helmet liners to mitigate traumatic brain injuries (TBI), with a focus on rotational acceleration. Evaluating three lattice unit cell topologies (simple cubic, dode-medium, and rhombic dodecahedron), the research builds upon prior investigations indicating that PA12 lattice liners may outperform conventional EPS liners. Employing a high-fidelity finite element male head model and utilizing direct and oblique impact scenarios, mechanical quantities, such as maximum principal strain (MPS) and shear strain, cumulative strain damage measure and intracranial pressure were measured at the tissue level in different brain regions. Results indicate that lattice liners, especially with dode-medium topology, exhibit promising reductions in brain tissue strains. On average, during oblique impacts, less than 1 % of the brain volume experienced an MPS level of 0.4 when the lattice liners were adopted, whereas that percentage was above 70 % with the expandable polystyrene (EPS) foam liners. Pressure-based assessments suggest that lattice liners may outperform EPS liners in oblique impacts, showcasing the limitations of EPS for effective TBI mitigation. Despite certain model limitations, this study emphasizes the need for advancements in helmet technology, particularly in the development of commercial lattice liners using additive manufacturing, to address the limitations of existing EPS liners in preventing rotational consequences of impacts and reducing TBI.

Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients.

Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a 'hot' tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.

Prognostic value of atypical B cells in breast cancer.

The impact of tumor-infiltrating B cells on breast cancer (BRCA) outcomes remains poorly understood. Recent findings from Yang et al. identify an atypical, clonally expanded population of activated Fc receptor-like 4 (FCRL4)+ B cells that is associated with improved overall survival in patients affected by various tumor types, including BRCA.

Improving the Lithography Sensitivity of Atomically Precise Tin-Oxo Nanoclusters via Heterometal Strategy.

Tin-oxo clusters are increasingly recognized as promising materials for nanolithography technology due to their unique properties, yet their structural impacts on lithography performance remain underexplored. This work explores the structural impacts of heterometal strategies on the performance of tin-oxo clusters in nanolithography, focusing on various metal dopants and their coordination geometries. Specifically, SnOC-1(In), SnOC-1(Al), SnOC-1(Fe), and SnOC-2 were synthesized and characterized. These clusters demonstrate excellent solubility, dispersibility, and stability, facilitating the preparation of high-quality films via spin-coating for lithographic applications. Notably, this work innovatively employs nano-infrared (nano-IR), neutron reflectivity (NR), and X-ray reflectivity (XRR) measurements to confirm film homogeneity. Upon electron beam lithography (EBL), all four materials achieve 50 nm line patterns, with SnOC-1(In) demonstrating the highest lithography sensitivity. This enhanced sensitivity is attributed to indium dopants, which possess superior EUV absorption capabilities and unsaturated coordination environments. Further studies on exposure mechanisms indicated that Sn-C bond cleavage generates butyl free radicals, promoting network formations that induce solubility-switching behaviors for lithography. These findings underscore the efficacy of tailored structural design and modulation of cluster materials through heterometal strategies in enhancing lithography performance, offering valuable insights for future material design and applications.

Towards dynamically configured databases for CIFs: the new modulated structures open database at the Bilbao Crystallographic Server.

This article presents a web-based framework to build a database without in-depth programming knowledge given a set of CIF dictionaries and a collection of CIFs. The framework consists of two main elements: the public site that displays the information contained in the CIFs in an ordered manner, and the restricted administrative site which defines how that information is stored, processed and, eventually, displayed. Thus, the web application allows users to easily explore, filter and access the data, download the original CIFs, and visualize the structures via JSmol. The modulated structures open database B-IncStrDB, the official International Union of Crystallography repository for this type of material and available through the Bilbao Crystallographic Server, has been re-implemented following the proposed framework.

SUBGROUPS: a computer tool at the Bilbao Crystallographic Server for the study of pseudo-symmetric or distorted structures.

SUBGROUPS is a free online program at the Bilbao Crystallographic Server (https://www.cryst.ehu.es/). It permits the exploration of all possible symmetries resulting from the distortion of a higher-symmetry parent structure, provided that the relation between the lattices of the distorted and parent structures is known. The program calculates all the subgroups of the parent space group which comply with this relation. The required minimal input is the space-group information of the parent structure and the relation of the unit cell of the distorted or pseudo-symmetric structure with that of the parent structure. Alternatively, the wavevector(s) observed in the diffraction data characterizing the distortion can be introduced. Additional conditions can be added, including filters related to space-group representations. The program provides very detailed information on all the subgroups, including group-subgroup hierarchy graphs. If a Crystallographic Information Framework (CIF) file of the parent high-symmetry structure is uploaded, the program generates CIF files of the parent structure described under each of the chosen lower symmetries. These CIF files may then be used as starting points for the refinement of the distorted structure under these possible symmetries. They can also be used for density functional theory calculations or for any other type of analysis. The power and efficiency of the program are illustrated with a few examples.

Revisiting the nature and pharmacodynamics of tacrolimus metabolites.

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers. To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo. In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers. Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction.

Cohomogeneity one solitons for the isometric flow of G 2 -structures.

We consider the existence of cohomogeneity one solitons for the isometric flow of G 2 -structures on the following classes of torsion-free G 2 -manifolds: the Euclidean R 7 with its standard G 2 -structure, metric cylinders over Calabi-Yau 3-folds, metric cones over nearly Kähler 6-manifolds, and the Bryant-Salamon G 2 -manifolds. In all cases we establish existence of global solutions to the isometric soliton equations, and determine the asymptotic behaviour of the torsion. In particular, existence of shrinking isometric solitons on R 7 is proved, giving support to the likely existence of type I singularities for the isometric flow. In each case, the study of the soliton equation reduces to a particular nonlinear ODE with a regular singular point, for which we provide a careful analysis. Finally, to simplify the derivation of the relevant equations in each case, we first establish several useful Riemannian geometric formulas for a general class of cohomogeneity one metrics on total spaces of vector bundles which should have much wider application, as such metrics arise often as explicit examples of special holonomy metrics.

The actin-binding protein palladin associates with the respiratory syncytial virus matrix protein.

The respiratory syncytial virus (RSV) matrix (M) protein plays an important role in infection as it can interact with viral components as well as the host cell actin microfilaments. The M-actin interaction may play a role in facilitating the transportation of virion components to the apical surface, where RSV is released. We show that M protein's association with actin is facilitated by palladin, an actin-binding protein. Cells were infected with RSV or transfected to express full-length M as a green fluorescent protein (GFP)-tagged protein, followed by removal of nuclear and cytosolic proteins to enrich for cytoskeleton and its associated proteins. M protein was present in inclusion bodies tethered to microfilaments in infected cells. In transfected cells, GFP-M was presented close to microfilaments, without association, suggesting the possible involvement of an additional protein in this interaction. As palladin can bind to proteins that also bind actin, we investigated its interaction with M. Cells were co-transfected to express GFP-M and palladin as an mCherry fluorescent-tagged protein, followed by cytoskeleton enrichment. M and palladin were observed to colocalize towards microfilaments, suggesting that palladin is involved in the M-actin interaction. In co-immunoprecipitation studies, M was found to associate with two isoforms of palladin, of 140 and 37 kDa. Interestingly, siRNA downregulation of palladin resulted in reduced titer of released RSV, while cell associated RSV titer increased, suggesting a role for palladin in virus release. Together, our data show that the M-actin interaction mediated by palladin is important for RSV budding and release.IMPORTANCERespiratory syncytial virus is responsible for severe lower respiratory tract infections in young children under 5 years old, the elderly, and the immunosuppressed. The interaction of the respiratory syncytial virus matrix protein with the host actin cytoskeleton is important in infection but has not been investigated in depth. In this study, we show that the respiratory syncytial virus matrix protein associates with actin microfilaments and the actin-binding protein palladin, suggesting a role for palladin in respiratory syncytial virus release. This study provides new insight into the role of the actin cytoskeleton in respiratory syncytial virus infection, a key host-RSV interaction in assembly. Understanding the mechanism by which the RSV M protein and actin interact will ultimately provide a basis for the development of therapeutics targeted at RSV infections.

CoNglyPred: Accurate Prediction of N-Linked Glycosylation Sites Using ESM-2 and Structural Features With Graph Network and Co-Attention.

N-Linked glycosylation is crucial for various biological processes such as protein folding, immune response, and cellular transport. Traditional experimental methods for determining N-linked glycosylation sites entail substantial time and labor investment, which has led to the development of computational approaches as a more efficient alternative. However, due to the limited availability of 3D structural data, existing prediction methods often struggle to fully utilize structural information and fall short in integrating sequence and structural information effectively. Motivated by the progress of protein pretrained language models (pLMs) and the breakthrough in protein structure prediction, we introduced a high-accuracy model called CoNglyPred. Having compared various pLMs, we opt for the large-scale pLM ESM-2 to extract sequence embeddings, thus mitigating certain limitations associated with manual feature extraction. Meanwhile, our approach employs a graph transformer network to process the 3D protein structures predicted by AlphaFold2. The final graph output and ESM-2 embedding are intricately integrated through a co-attention mechanism. Among a series of comprehensive experiments on the independent test dataset, CoNglyPred outperforms state-of-the-art models and demonstrates exceptional performance in case study. In addition, we are the first to report the uncertainty of N-linked glycosylation predictors using expected calibration error and expected uncertainty calibration error.

Octahedral vs Tiara-like Pd6(SR)12 Clusters.

Atomically precise Pd-thiolate clusters are well-known for their well-defined structures and diverse applications involving catalysis, sensors, and biomedicine. While many of these clusters have been studied, their molecular structures typically feature a tiara-like arrangement. In this study, we present the first example of a non-tiara-like Pd-thiolate cluster: the octahedral Pd6(SC6H11)12 (denoted as Pd6-Oct). The composition and geometric structure of the cluster were characterized using electrospray ionization mass spectrometry (ESI-MS) together with single-crystal X-ray diffraction (SXRD). Despite having a similar chemical composition to tiara-like Pd6(SC2H4Ph)12 (denoted as Pd6-Tia), Pd6-Oct exhibits a distinctly different geometric structure. Additionally, UV-vis-NIR absorption spectroscopy combined with quantum chemical calculations provided valuable insights into the electronic structures of these clusters. The excited-state dynamics, host-guest chemistry, and the catalytic properties of Pd6-Oct and Pd6-Tia were examined to compare their structure-property relationships. This research represents significant advances in the synthesis and understanding of structure-property correlations in Pd-thiolate clusters.

Exploring the impact of tertiary lymphoid structures maturity in NSCLC: insights from TLS scoring.

Tertiary Lymphoid Structures (TLS) are lymphoid structures commonly associated with improved survival of cancer patients and response to immunotherapies. However, conflicting reports underscore the need to consider TLS heterogeneity and multiple features such as TLS size, composition, and maturation status, when assessing their functional impact. With the aim of gaining insights into TLS biology and evaluating the prognostic impact of TLS maturity in Non-Small Cell Lung Carcinoma (NSCLC), we developed a multiplex immunofluorescent (mIF) panel including T cell (CD3, CD8), B cell (CD20), Follicular Dendritic cell (FDC) (CD21, CD23) and mature dendritic cell (DC-LAMP) markers. We deployed this panel across a cohort of primary tumor resections from NSCLC patients (N=406) and established a mIF image analysis workstream to specifically detect TLS structures and evaluate the density of each cell phenotype. We assessed the prognostic significance of TLS size, number, and composition, to develop a TLS scoring system representative of TLS biology within a tumor. TLS relative area, (total TLS area divided by the total tumor area), was the most prognostic TLS feature (C-index: 0.54, p = 0.04). CD21 positivity was a marker driving the favorable prognostic impact, where CD21+ CD23- B cells (C-index: 0.57, p = 0.04) and CD21+ CD23- FDC (C-index: 0.58, p = 0.01) were the only prognostic cell phenotypes in TLS. Combining the three most robust prognostic TLS features: TLS relative area, the density of B cells, and FDC CD21+ CD23- we generated a TLS scoring system that demonstrated strong prognostic value in NSCLC when considering the effect of age, sex, histology, and smoking status. This TLS Score also demonstrated significant association with Immunoscore, EGFR mutational status and gene expression-based B-cell and TLS signature scores. It was not correlated with PD-L1 status in tumor cells or immune cells. In conclusion, we generated a prognostic TLS Score representative of the TLS heterogeneity and maturity undergoing within NSCLC tissues. This score could be used as a tool to explore how TLS presence and maturity impact the organization of the tumor microenvironment and support the discovery of spatial biomarker surrogates of TLS maturity, that could be used in the clinic.

3D Tunnel Copper Tetrathiovanadate Nanocube Cathode Achieving Ultrafast Magnesium Storage Reactions through a Charge Delocalization and Displacement Mechanism.

Rechargeable magnesium batteries are attractive candidates for large-scale energy storage applications because of the low cost and high safety, but the scarcity and inferior performance of the cathode materials are hindering the development. In the present study, a kind of copper tetrathiovanadate (Cu3VS4) cathode is designed and developed with a comprehensive consideration of the chemical and electronic structures. The vanadium and sulfur atoms form chemical bonds with high covalent proportion, facilitating electron delocalization via the vanadium-sulfur bonds. This reduces the interaction with the bivalent magnesium cation and induces the coredox of vanadium and sulfur. The crystal structure of Cu3VS4 has interlaced 3D tunnels for solid-state magnesium cation transport. The Cu3VS4 cathode shows a high capacity of 350 mA h g-1 at 100 mA g-1, an outstanding rate performance of 67 mA h g-1 at 10 A g-1, and stable cycling for 1000 cycles at 5 A g-1 without obvious capacity fading. Prominently, a high areal mass load of 3.5 mg cm-2 could be achieved without obvious rate capability decay, which is quite favorable to pair with the high-capacity magnesium metal anode in practical application. The mechanism investigation and theoretical computation demonstrate that Cu3VS4 undergoes first a magnesium intercalation and then a displacement reaction, during which the crystal structure is maintained, assisting the reaction reversibility and cycling stability. All the copper, vanadium, and sulfur elements experience redox and contribute to the high capacity. Moreover, the weakened interaction with magnesium cations, well-kept 3D cation transport tunnels, and high electronic conductivity result in the superior rate performance and high areal active material loading. The present study develops a high-performance cathode for rechargeable magnesium batteries and reveal the design principle based on both of chemical and electronic structures.

Round robin experiment to detect, size, and characterize flaws in the welds of existing hydraulic steel structures using phased array ultrasonic testing.

Limited information exists on the ability of nondestructive testing techniques to detect, size, and characterize flaws in existing hydraulic steel structures (HSS). Round robin experiments were conducted using phased array ultrasonics to inspect welded steel specimens representing joints in existing HSS. Technicians detected 83% of the flaws scanned, but detection rates varied widely by flaw and technician. Uncertainty in flaw size estimates, represented by 90% confidence bounds on the ratio of estimated to actual length or height, ranged from 0.52 to 2.10 for length and 0.32 to 3.59 for height. Planar, volumetric and laminar flaws were accurately characterized 80% of the time.