Proton Transport Scenarios in Sulfuric Acid Explored via Ab Initio Molecular Dynamics Simulations.

Sulfuric acid (H2SO4), a highly reactive reagent containing intrinsic protonic charge carriers, has been studied via ab initio molecular dynamics simulations. Specifically, we explore the solvation shell structure of the protonic defects, H1SO4- and H3SO4+, as well as the underlying proton transport mechanisms in both the neat and hydrated H2SO4 solutions. Our findings reveal a significant contraction of the dynamic hydrogen-bonded network around the protonic defects, which resembles features seen in water. The simulations provide estimates of the structural relaxation time scales for proton release from both the covalent O-H bonds (∼23 ps) and the hydrogen bonds (∼0.4 ps). In contrast to water, our analysis of the proton transfer scenarios in sulfuric acid reveals correlated events mediated by the formation of longer (up to four) hydrogen-bonded Grotthuss chains.

State assault weapons bans are associated with fewer fatalities: analysis of US county mass shooting incidents (2014-2022).

BACKGROUND: The need for evidence to inform interventions to prevent mass shootings (MS) in the USA has never been greater. METHODS: Data were abstracted from the Gun Violence Archive, an independent online database of US gun violence incidents. Descriptive analyses consisted of individual-level epidemiology of victims, suspected shooters and weapons involved, trends and county-level choropleths of population-level incident and fatality rates. Counties with and without state-level assault weapons bans (AWB) were compared, and we conducted a multivariable negative binomial model controlling for county-level social fragmentation, median age and number of gun-related homicides for the association of state-level AWB with aggregate county MS fatalities. RESULTS: 73.3% (95% CI 72.1 to 74.5) of victims and 97.2% (95% CI 96.3 to 98.3) of shooters were males. When compared with incidents involving weapons labelled 'handguns', those involving a weapon labelled AR-15 or AK-47 were six times more likely to be associated with case-fatality rates greater than the median (OR=6.1, 95% CI 2.3 to 15.8, p<0.00001). MS incidents were significantly more likely to occur on weekends and during summer months. US counties in states without AWB had consistently higher MS rates throughout the study period (p<0.0001), and the slope for increase over time was significantly lower in counties with AWB (beta=-0.11, p=0.01). In a multivariable negative binomial model, counties in states with AWB were associated with a 41% lower incidence of MS fatalities (OR=0.58, 95% CI 0.37 to 0.97, p=0.02). CONCLUSIONS: Counties located in states with AWB were associated with fewer MS fatalities between 2014 and 2022.

Biobased self-healing thin film coatings based on poly(itaconic acid esters).

Paper used for packaging applications is often coated with thin polymer coatings to improve the properties, like printability and barrier properties, respectively. Today, these coatings are still often based on petroleum-based polymers. In this study, the fabrication of biobased thin film coatings is described. Poly(itaconic acid ester)s, which are prepared by emulsion poly-meri-zation, are used as water-based coatings for paper. The thermal properties of the polymers are tuned by the side chain of the monomers (diethyl itaconate vs. dibutyl itaconate). Different formulations based on the polymer emulsion and additives, like rheology modifiers, are prepared and their film formation is studied. The usage of Rheobyk-7420 CA as rheology modifier results in excellent film formation. These polymer coatings feature an additional function - they are capable of self-healing. The healing ability is studied in scratch healing tests, in which almost complete recovery can be observed after healing at 100 °C. Moreover, the restoration of optical properties / aesthetics is studied. In gloss measurements before and after damage as well as after a healing time the complete recovery of the gloss can be observed. Furthermore, the barrier properties against fat are studied.

Understanding Strain and Failure of a Knot in Polyethylene Using Molecular Dynamics with Machine-Learned Potentials.

A neural network potential (NNP) has been developed by fitting to ab initio electronic structure data on hydrocarbons and is used to study failure of linear and knotted polyethylene (PE) chains. A linear PE chain must be highly strained before breaking as the stress is equally distributed across the chain. In contrast, the stress in a PE chain with a 31 or overhand knot, accumulates at the knot's entrance/exit. We find the strain energy is greatest when the bond length and angle are strained simultaneously, and that the knot weakens the chain by increasing the variance of the C-C-C angle, thereby allowing rupture at lower bond strains. We extend our analysis to both 51 and 52 knots and find that both break at the entrance/exit of a loop. Notably, molecular scale PE knots exhibit many of the same characteristics as knots in a macroscopic rope, with stick-slip phenomena upon tightening and similar points of failure.

A widespread electrical brain network encodes anxiety in health and depressive states.

In rodents, anxiety is charactered by heightened vigilance during low-threat and uncertain situations. Though activity in the frontal cortex and limbic system are fundamental to supporting this internal state, the underlying network architecture that integrates activity across brain regions to encode anxiety across animals and paradigms remains unclear. Here, we utilize parallel electrical recordings in freely behaving mice, translational paradigms known to induce anxiety, and machine learning to discover a multi-region network that encodes the anxious brain-state. The network is composed of circuits widely implicated in anxiety behavior, it generalizes across many behavioral contexts that induce anxiety, and it fails to encode multiple behavioral contexts that do not. Strikingly, the activity of this network is also principally altered in two mouse models of depression. Thus, we establish a network-level process whereby the brain encodes anxiety in health and disease.

DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

BACKGROUND: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS. METHODS: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing. RESULT: Our study shows high-grade CFOS demonstrate highly complex and heterogenous genomic alterations and harbor frequently mutated tumor suppressor genes TP53, CDKN2A/B, and PTEN, similar to conventional osteosarcomas. Potentially actionable gene amplifications involving CCNE1, AKT2, MET, NTRK1, PDGFRA, KDR, KIT, MAP3K14, FGFR1, and AURKA were seen in 43% of cases. GNAS hotspot activating mutations were also identified in a subset of CFOS cases, with one case representing malignant transformation from fibrous dysplasia, suggesting a role for GNAS mutation in the development of CFOS. CONCLUSION: High-grade CFOS demonstrate highly complex and heterogenous genomic alterations, with amplification involving receptor tyrosine kinase genes, and frequent mutations involving tumor suppressor genes.

Osteoblastoma of the thumb with a novel PRSS44::ALK fusion and literature review of osteoblastoma of hands and feet bones.

Osteoblastomas (OBs) are benign neoplasms constituting approximately 1% of primary bone tumors with a predilection for the spine and sacrum. We describe an OB of the proximal phalanx of the left thumb in a 38-year-old female. MRI of left hand demonstrated a 29-mm mildly expansile enhancing lesion involving the entire proximal phalanx of the first digit. Histology displayed a bone-forming tumor consisting of trabeculae of remodeled woven bone framed by plump osteoblasts in a vascularized background. Next-generation sequencing analysis identified a PRSS44::ALK fusion gene.

Synchronous Low-Grade Central Osteosarcoma and Ewing Sarcoma: A Rare Case Report.

A 23-year-old female patient presented with radicular back pain, perineal numbness, and urinary retention. The patient was diagnosed with cauda equina syndrome and magnetic resonance imaging (MRI) of the spine revealed an enhancing osseous lumbar lesion causing severe central stenosis. A core needle biopsy of the lumbar spine showed microscopic features compatible with a small round blue cell tumor. CD99 and FLI1 were positive in the tumor cells. Next-generation sequencing demonstrated a EWSR1::FLI1 fusion. Given these findings, the spine lesion was diagnosed as Ewing sarcoma. The patient underwent surgical decompression of L2. On further workup, an MRI revealed an ill-defined enhancing mass of the right distal femur. This area was biopsied, demonstrating a fibro-osseous lesion with osteoblast proliferation containing nuclear atypia, low mitotic activity, and SATB2 positivity, diagnosed as low-grade central osteosarcoma (LGCOS). The patient underwent resection, which showed a classic LGCOS by histomorphology. Although fluorescence in-situ hybridization study for MDM2 gene amplification was negative, the overall findings are most consistent with LGCOS. These neoplasms are considered to be synchronous due to the presentation of each entity within 6 months. Considering the aggregate yearly incidence of Ewing sarcoma (approximately 1 case per 750 000 per year) and LGCOS (approximately 1 case per 10 million per year), the aggregate yearly probability of developing both of these genetically unrelated tumors in a single individual is 1 per 7.5 trillion per year, and it is likely such an event has never happened in the past.

Non-neoplastic bone, joint, and soft tissue pathology: What every pathologist should know.

The diagnosis of bone and soft tissue tumors is a skill which requires experience across multiple disciplines while their incidence is small. By contrast, the numbers of patients with non-tumorous diseases of bones, soft tissues, and joints dwarfs primary tumors by several orders of magnitude. The ability to successfully diagnose non-neoplastic diseases requires a knowledge of bone development, structure, remodeling, imaging, and tissue processing. This review summarizes the alterations of bones, joints, and to a lesser extent soft tissues that are encountered in the practice of everyday surgical pathology.

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration.

Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a 2 d differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7 tesla (7 T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS-. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting postacquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.

Sclerosing epithelioid fibrosarcoma of bone with hybrid features: clinicopathologic, radiologic, and molecular analysis of three cases.

Sclerosing epithelioid fibrosarcoma (SEF) occurring as a primary bone tumor is exceptionally uncommon. Even more rare are cases of SEF that show morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Such hybrid lesions arising within the bone have only rarely been reported in the literature. Due to their variegated histomorphology and non-specific radiologic features, these tumors may pose diagnostic difficulties. Herein we describe three molecularly confirmed primary bone cases of sclerosing epithelioid fibrosarcoma that demonstrated prominent areas showing the features of LGFMS and with areas resembling so-called hyalinizing spindle cell tumor with giant rosettes (HSCTGR). Two patients were female and one was male aged 26, 47, and 16, respectively. The tumors occurred in the femoral head, clavicle, and temporal bone. Imaging studies demonstrated relatively well-circumscribed radiolucent bone lesions with enhancement on MRI. Cortical breakthrough and soft tissue extension were present in one case. Histologically the tumors all demonstrated hyalinized areas with SEF-like morphology as well as spindled and myxoid areas with LGFMS-like morphology. Two cases demonstrated focal areas with rosette-like architecture as seen in HSCTGR. The tumors were all positive for MUC4 by immunohistochemistry and cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing studies identified EWSR1 gene rearrangements confirming the diagnosis in all three cases.Hybrid SEF is exceedingly rare as a primary bone tumor and can be difficult to distinguish from other low-grade spindled and epithelioid lesions of bone. MUC4 positivity and identification of underlying EWSR1 gene rearrangements help support this diagnosis and exclude other tumor types.

Glycan-Driven Formation of Raft-Like Domains with Hierarchical Periodic Nanoarrays on Dendrimersome Synthetic Cells.

The accurate spatial segregation into distinct phases within cell membranes coordinates vital biochemical processes and functionalities in living organisms. One of nature's strategies to localize reactivity is the formation of dynamic raft domains. Most raft models rely on liquid-ordered L0 phases in a liquid-disordered Ld phase lacking correlation and remaining static, often necessitating external agents for phase separation. Here, we introduce a synthetic system of bicomponent glycodendrimersomes coassembled from Janus dendrimers and Janus glycodendrimers (JGDs), where lactose-lactose interactions exclusively drive lateral organization. This mechanism results in modulated phases across two length scales, yielding raft-like microdomains featuring nanoarrays at the nanoscale. By varying the density of lactose and molecular architecture of JGDs, the nanoarray type and size, shape, and spacing of the domains were controlled. Our findings offer insight into the potential primordial origins of rudimentary raft domains and highlight the crucial role of glycans within the glycocalyx.

Sequencing by avidity enables high accuracy with low reagent consumption.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer-nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

Diabetic Ketoacidosis and Acute Kidney Injury Associated With Enfortumab Vedotin for Urothelial Carcinoma: A Case Report.

Enfortumab vedotin is a novel breakthrough therapy that received accelerated US Food and Drug Administration approval in 2019 for the treatment of metastatic urothelial carcinoma in patients who have failed other lines of treatment. The characteristics of its adverse effects are not well understood. Diabetic ketoacidosis has been reported in 2 postmarketing reports presented as abstracts at the 2020 American Thoracic Society Conference and the 2021 American Society of Nephrology Conference. Both cases progressed rapidly and expired in <3 days. We present a similar case of a man in his late 50s with no history of diabetes who was diagnosed with urothelial carcinoma 2 years prior. Despite several lines of treatment, including platinum-based chemotherapy and immune checkpoint inhibitors, he developed metastasis and was started on enfortumab vedotin. After his second dose of enfortumab vedotin, he was admitted to the intensive care unit for diabetic ketoacidosis with an initial A1C level of 7.7%. He was intubated for airway protection, started on pressors, and developed oliguric acute kidney injury requiring continuous venovenous hemodialysis. Despite aggressive treatment, the patient died on hospital day 2. The lethality of this aggressive diabetic ketoacidosis despite therapy suggests some other effect of enfortumab vedotin on glucose metabolism in addition to insulin resistance and the need for prior diabetes screening.

Full-arch restoration with the NEXUS IOS® system: A retrospective clinical evaluation of 37 restorations after a one year of follow-up.

OBJECTIVES: Report the results with a novel workflow of digital restoration for completely edentulous patients with implant supported full arch fixed dental prostheses (ISFDP). METHODS: This multicenter retrospective clinical study was based on the evaluation from a cohort of 29 patients restored with 37 ISFDP designed and manufactured from the data captured by a direct intraoral scan, using a novel full digital system (NEXUS IOS®, Osteon Medical, a Keystone Dental Group company, Melbourne, Australia). Data was collected over a 3-year period, in six different dental centers. This study reported on the clinical parameters including: precision of marginal fit, functional and aesthetic integration of Nexus ISFDP. All patients were followed for a period of one year post delivery. Implant survival, biologic and prosthetic complications were assessed, at one year. A statistical analysis was conducted. RESULTS: All 37 ISFDP were deemed clinically acceptable on insertion. Implant survival at one year was 100 %. The biologic and prosthetic complications were minimal during the follow-up period. CONCLUSIONS: ISFDP, designed and manufactured using the NEXUS IOS® system, are clinically acceptable, with a low incidence of complications at one year. Long-term clinical studies are needed. STATEMENT OF CLINICAL RELEVANCE: Within the limitations of this study (retrospective design, small patient sample, limited follow-up) the NEXUS IOS® system seems to represent a viable solution for the restoration of completely edentulous patients with ISFDP, in a full digital workflow.

Understanding the Anomalous Diffusion of Water in Aqueous Electrolytes Using Machine Learned Potentials.

The diffusivity of water in aqueous cesium iodide solutions is larger than that in neat liquid water and vice versa for sodium chloride solutions. Such peculiar ion-specific behavior, called anomalous diffusion, is not reproduced in typical force field based molecular dynamics (MD) simulations due to inadequate treatment of ion-water interactions. Herein, this hurdle is tackled by using machine learned atomic potentials (MLPs) trained on data from density functional theory calculations. MLP based atomistic MD simulations of aqueous salt solutions reproduce experimentally determined thermodynamic, structural, dynamical, and transport properties, including their varied trends in water diffusivities across salt concentration. This enables an examination of their intermolecular structure to unravel the microscopic underpinnings of the differences in their transport properties. While both ions in CsI solutions contribute to the faster diffusion of water molecules, the competition between the heavy retardation by Na ions and the slight acceleration by Cl ions in NaCl solutions reduces their water diffusivity.

Why Dissolving Salt in Water Decreases Its Dielectric Permittivity.

The dielectric permittivity of salt water decreases on dissolving more salt. For nearly a century, this phenomenon has been explained by invoking saturation in the dielectric response of the solvent water molecules. Herein, we employ an advanced deep neural network (DNN), built using data from density functional theory, to study the dielectric permittivity of sodium chloride solutions. Notably, the decrease in the dielectric permittivity as a function of concentration, computed using the DNN approach, agrees well with experiments. Detailed analysis of the computations reveals that the dominant effect, caused by the intrusion of ionic hydration shells into the solvent hydrogen-bond network, is the disruption of dipolar correlations among water molecules. Accordingly, the observed decrease in the dielectric permittivity is mostly due to increasing suppression of the collective response of solvent waters.