Surgeon preference for maximizing medical care is associated with recommending more extensive surgery for low-risk thyroid cancer.

BACKGROUND: While patient-level determinants of total thyroidectomy use have been well described, surgeon-level drivers of more extensive surgery are present and less well described. This survey sought to examine the associations between surgeons' operative recommendations, their beliefs about cancer, and their attitudes about medical maximizing-minimizing. METHODS: A mixed-mode, cross-sectional survey was administered in September 2020 via mail and email to 222 thyroid surgeons identified in the Centers for Medicare & Medicaid Services (CMS) Provider Utilization and Payment Physician and Other Practitioners dataset. Participants were asked their treatment recommendation for a healthy 45-year-old woman with a solitary 2.0-cm PTC. Surgeons were assessed with the Brief Worry Scale and a validated, single-item measure of cancer-related worry. The Clinician Maximizer-Minimizer scale was used to assess the extent of medical care that physicians tend to favor with their patients. Participants were categorized into terciles based on their responses to the Maximizer-Minimizer scale. The highest scoring tercile ("Maximizers") was compared to the two lower terciles by Student's t-tests, Chi-square, ANOVA, and logistic regression. RESULTS: Of the 149 surgeons (response rate 67.1%), 34.9% recommended total thyroidectomy with or without CND and 65.1% recommended lobectomy. Overall, the medical Maximizer-Minimizer scale had an average score of 24.6 (SD 6.8). There were no differences between surgeons' age, race, annual thyroidectomy volume, or practice setting by their Maximizer-Minimizer classification. Participants who recommended total thyroidectomy with or without CND had significantly higher Maximizer-Minimizer scores than those recommending lobectomy (25.9±7.2 vs. 23.8±6.4, p=0.03). Those classified as maximizers also had more cancer-related worry on both the single-item and Brief Worry Scales (p=0.02). On logistic regression controlling for age, sex, race, specialty training, practice setting, and annual thyroidectomy volume, maximizers were still more likely to recommend total thyroidectomy with or without a CND (OR 2.4, 95% C.I. 1.01 - 5.55, p=0.047). CONCLUSIONS: Medical maximizing-minimizing tendencies represent one of potentially many unmeasured surgeon characteristics that may explain persistent patterns of over-diagnosis, over-treatment, and over-screening. Surgeons may benefit from awareness of how their own tendencies influence their surgical recommendations in patients with low-risk thyroid cancer.

TIR domains of TLR family-from the cell culture to the protein sample for structural studies.

Toll-like receptors (TLRs) are key players in the innate immune system. Despite the great efforts in TLR structural biology, today we know the spatial structures of only four human TLR intracellular TIR domains. All of them belong to one of five subfamilies of receptors. One of the main bottlenecks is the high-level production of correctly folded proteins in soluble form. Here we used a rational approach to find the optimal parameters to produce TIR domains of all ten human TLR family members in soluble form in E. coli cells. We showed that dozens of milligrams of soluble His-tagged TLR2/3/6/7TIR and MBP-tagged TLR3/5/7/8TIR can be produced. We also developed the purification protocols and demonstrated by CD and NMR spectroscopy that purified TLR2/3/7TIR demonstrate a structural organization inherent to TIR domains. This illustrates the correct folding of produced proteins and their suitability for further structural and functional investigations.

Fluorescence lifetime multiplexing with fluorogen activating protein FAST variants.

In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling.

Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.

Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes.

Retrospective for the Dynamic Sensorium Competition for predicting large-scale mouse primary visual cortex activity from videos.

Understanding how biological visual systems process information is challenging because of the nonlinear relationship between visual input and neuronal responses. Artificial neural networks allow computational neuroscientists to create predictive models that connect biological and machine vision. Machine learning has benefited tremendously from benchmarks that compare different model on the same task under standardized conditions. However, there was no standardized benchmark to identify state-of-the-art dynamic models of the mouse visual system. To address this gap, we established the Sensorium 2023 Benchmark Competition with dynamic input, featuring a new large-scale dataset from the primary visual cortex of ten mice. This dataset includes responses from 78,853 neurons to 2 hours of dynamic stimuli per neuron, together with the behavioral measurements such as running speed, pupil dilation, and eye movements. The competition ranked models in two tracks based on predictive performance for neuronal responses on a held-out test set: one focusing on predicting in-domain natural stimuli and another on out-of-distribution (OOD) stimuli to assess model generalization. As part of the NeurIPS 2023 competition track, we received more than 160 model submissions from 22 teams. Several new architectures for predictive models were proposed, and the winning teams improved the previous state-of-the-art model by 50%. Access to the dataset as well as the benchmarking infrastructure will remain online at www.sensorium-competition.net.

Transient Covalency in Molten Uranium(III) Chloride.

Uranium is arguably the most essential element in the actinide series, serving as a crucial component of nuclear fuels. While U is recognized for engaging the 5f orbitals in chemical bonds under normal conditions, little is known about its coordination chemistry and the nature of bonding interactions at extreme conditions of high temperature. Here we report experimental and computational evidence for the shrinkage of the average U-ligand distance in UCl3 upon the solid-to-molten phase transition, leading to the formation of a significant fraction of short, transient U-Cl bonds with the enhanced involvement of U 5f valence orbitals. These findings reveal that extreme temperatures create an unusual heterogeneous bonding environment around U(III) with distinct inner- and outer-coordination subshells.

Genomics and taxonomy of the glyphosate-degrading, copper-tolerant rhizospheric bacterium Achromobacter insolitus LCu2.

A rhizosphere strain, Achromobacter insolitus LCu2, was isolated from alfalfa (Medicago sativa L.) roots. It was able to degrade of 50% glyphosate as the sole phosphorus source, and was found resistant to 10 mM copper (II) chloride, and 5 mM glyphosate-copper complexes. Inoculation of alfalfa seedlings and potato microplants with strain LCu2 promoted plant growth by 30-50%. In inoculated plants, the toxicity of the glyphosate-copper complexes to alfalfa seedlings was decreased, as compared with the noninoculated controls. The genome of A. insolitus LCu2 consisted of one circular chromosome (6,428,890 bp) and encoded 5843 protein genes and 76 RNA genes. Polyphasic taxonomic analysis showed that A. insolitus LCu2 was closely related to A. insolitus DSM23807T on the basis of the average nucleotide identity of the genomes of 22 type strains and the multilocus sequence analysis. Genome analysis revealed genes putatively responsible for (1) plant growth promotion (osmolyte, siderophore, and 1-aminocyclopropane-1-carboxylate deaminase biosynthesis and auxin metabolism); (2) degradation of organophosphonates (glyphosate oxidoreductase and multiple phn clusters responsible for the transport, regulation and C-P lyase cleavage of phosphonates); and (3) tolerance to copper and other heavy metals, effected by the CopAB-CueO system, responsible for the oxidation of copper (I) in the periplasm, and by the efflux Cus system. The putative catabolic pathways involved in the breakdown of phosphonates are predicted. A. insolitus LCu2 is promising in the production of crops and the remediation of soils contaminated with organophosphonates and heavy metals.

Dynamic Ion Gels from the Complex Coacervation of Oppositely Charged Poly(ionic liquid)s.

A cationic poly(ionic liquid) (PIL) with pendent butyl imidazolium cations and free bis(trifluoromethylsulfonyl)imide (TFSI) anions and an anionic PIL with pendent TFSI anions and free 1-butyl-3-methylimidazolium cations are synthesized by postpolymerization chemical modification and reversible addition-fragmentation chain-transfer radical copolymerization, respectively. Upon mixing solutions of these two PILs in acetone with stoichiometric amounts of ion pairs, ionic exchanges induce coacervation and, after solvent evaporation, lead to the formation of a dynamic ion gel (DIG) and the concomitant release of free [1-methyl-3-butyl imidazolium]TFSI ionic liquid (IL). A comparison of thermal (Tg), ion conducting (σDC), and viscoelastic (elastic moduli (G')) properties for DIGs and their parent polyelectrolytes, as well as extracted and IL-doped DIGs, demonstrates the formation of ionic cross-links and the ability to easily produce polymer electrolytes with enhanced ionic conductivity (σDC up to 4.5 × 10-5 S cm-1 at 30 °C) and higher elastic moduli (G' up to 4 kPa at 25 °C and 1 rad s-1), making them highly desirable in many electrochemical applications, including supercapacitors, soft robotics, electrochromic devices, sensors, and solar cells.

SACCHARIS v2: Streamlining Prediction of Carbohydrate-Active Enzyme Specificities Within Large Datasets.

Carbohydrates are chemically and structurally diverse, composed of a wide array of monosaccharides, stereochemical linkages, substituent groups, and intermolecular associations with other biological molecules. A large repertoire of carbohydrate-active enzymes (CAZymes) and enzymatic activities are required to form, dismantle, and metabolize these complex molecules. The software SACCHARIS (Sequence Analysis and Clustering of CarboHydrate Active enzymes for Rapid Informed prediction of Specificity) provides a rapid, easy-to-use pipeline for the prediction of potential CAZyme function in new datasets. We have updated SACCHARIS to (i) simplify its installation by re-writing in Python and packaging for Conda; (ii) enhance its usability through a new (optional) interactive GUI; and (iii) enable semi-automated annotation of phylogenetic tree output via a new R package or the commonly-used webserver iTOL. Significantly, SACCHARIS v2 has been developed with high-throughput omics in mind, with pipeline automation geared toward complex (meta)genome and (meta)transcriptome datasets to reveal the total CAZyme content ("CAZome") of an organism or community. Here, we outline the development and use of SACCHARIS v2 to discover and annotate CAZymes and provide insight into complex carbohydrate metabolisms in individual organisms and communities.

Electrospun Composites of Chitosan with Cerium Oxide Nanoparticles for Wound Healing Applications: Characterization and Biocompatibility Evaluation In Vitro and In Vivo.

Cerium oxide nanoparticles (CeONPs), as part of tissue regeneration matrices, can protect cells from reactive oxygen species and oxidative stress. In addition, they can influence the properties of the scaffold, including its electrospinnability and mechanical strength. In this work, we prepared electrospun fiber mats from a chitosan and polyethylene oxide blend (CS-PEO) with the addition of ceria nanoparticles (CS-PEO-CeONP). The addition of CeONPs resulted in a smaller fiber diameter and higher swelling compared to CS-PEO fiber mats. CeONP-modified fiber mats also had a higher Young's modulus due to the reinforcing effect of the nanoparticles. Both mats had comparable adhesion and cytocompatibility to mesenchymal stem cells, which had a more rounded morphology on CS-PEO-CeONP compared to elongated cells on the CS-PEO mats. Biocompatibility in an in vivo rat model showed no acute toxicity, no septic or allergic inflammation, and no rough scar tissue formation. The degradation of both mats passed the stage of matrix swelling. CS-PEO-CeONP showed significantly slower biodegradation, with most of the matrix remaining in the tissue after 90 days. The reactive inflammation was aseptic in nature with the involvement of multinucleated foreign-body type giant cells and was significantly reduced by day 90. CeONPs induced the formation of the implant's connective tissue capsule. Thus, the introduction of CeONPs influenced the physicochemical properties and biological activity of CS-PEO nanofiber mats.

Forecasting the need for palliative and hospice care using the creeping trend method with segment smoothing.

OBJECTIVE: Aim: To determine the limits of refinement of the forecast of the need for palliative and hospice care (PHC) among adults and children, made by the methods of linear, logarithmic and exponential trends, using the improved forecasting method. PATIENTS AND METHODS: Materials and Methods: Based on the calculated demand for 2018-2020, a demand forecast was made using the linear trend method for 2021 and 2022, which was verified by comparing it with the calculation based on available statistical data for 2022. To improve the forecasting result, the creeping trend method with a smoothing segment was used. RESULTS: Results: The estimated need for PHC by the linear trend method for 2022 was 87,254 adults and 46,122 children. The predicted need for this year by the linear trend method was 172,303 for adults and 45,517 for children. The prediction using the sliding trend method with segment smoothing was found to be 4.7 times more accurate and reliable for adults and all age groups combined, but was less accurate and not reliable for children. It was found out that in order to achieve a reliable forecast, it is necessary to clarify the data of medical statistics regarding of malignant neoplasms and congenital malformations, as well as demographic statistics. CONCLUSION: Conclusions: The method of a creeping trend gave more accurate results and made it possible to determine the reliability of the forecast, allowed to take into account the simultaneous influence of various input parameters.

A general approach to construct selenopheno[3,2-b]indole-cored molecules using Fischer indolization.

A wide series of various selenopheno[3,2-b]indole-based compounds, including 2-aryl-substituted selenopheno[3,2-b]indoles as well as derivatives of benzo[4,5]selenopheno[3,2-b]indole, pyrido[3',2':4,5]selenopheno[3,2-b]indole, pyrazino[2',3':4,5]selenopheno[3,2-b]indole and chromeno[3',4':4,5]selenopheno[3,2-b]indol-6-one, were prepared from the appropriate 3-aminoselenophen-2-carboxylates via a one-pot two-step procedure based on the Fischer indole synthesis. The present synthetic strategy includes the conversion of 3-aminoselenophen-2-carboxylates into 2-unsubstituted 3-aminoselenophenes, their C-2 protonation to form selenophen-3(2H)-iminium cations, and the reaction of these iminium intermediates with arylhydrazines to obtain arylhydrazones of selenophen-3(2H)-ones followed by their Fischer indolization affording selenopheno[3,2-b]indole molecules.

Is nicotine vaping associated with subsequent initiation of cannabis or other substances from adolescence into young adulthood?

Prior studies estimating longitudinal associations between nicotine vaping and subsequent initiation of cannabis and other substances (e.g., cocaine, heroin) have been limited by short follow-up periods, convenience sampling, and possibly inadequate confounding control. We sought to address some of these gaps using the nationally representative Population Assessment of Tobacco and Health Study (PATH) to estimate longitudinal associations between nicotine vaping and the initiation of cannabis or other substances among adolescents transitioning to adulthood from2013 to 2019, adjusting for treatment-confounder feedback. Estimands like the longitudinal average treatment effect were not identified because of extensive practical positivity violations. Therefore, we estimated longitudinal incremental propensity score effects, which were identified. We found that reduced odds of nicotine vaping were associated with decreased risks of cannabis or other substance initiation; these associations strengthened over time. For example, by the final wave (2018-19), cannabis and other substance initiation risks were 6.2 (95%CI:4.6-7.7) and 1.8 (95%CI:0.4-3.2) percentage points lower when odds of nicotine vaping were reduced to be 90% lower in all preceding waves (2013-14 to 2016-18), as compared with observed risks. Strategies to lower nicotine vaping prevalence during this period may have resulted in fewer young people initiating cannabis and other substances.

Voriconazole successfully treats chytridiomycosis in frogs.

Chytridiomycosis is a devastating disease and is a key cause of amphibian population declines around the world. Despite active research on this amphibian disease system for over 2 decades, we still do not have treatment methods that are safe and that can be broadly used across species. Here, we show evidence that voriconazole is a successful method of treatment for 1 species of amphibian in captivity and that this treatment could offer benefits over other treatment options like heat or itraconazole, which are not able to be used for all species and life stages. We conducted 2 treatments of chytridiomycosis using voriconazole. The treatment was effective and resulted in 100% pathogen clearance, and mortality ceased. Additionally, treating frogs with voriconazole requires less handling than treatment methods like itraconazole and requires no specialized equipment, like heat treatment. We highlight that clinical treatment trials should be conducted to identify an optimum dosage and treatment time and that trials should test whether this treatment is safe and effective for tadpoles and other species.

Synthesis of Cs3Cu2I5 Nanocrystals in a Continuous Flow System.

Achieving the goal of generating all of the world's energy via renewable sources and significantly reducing the energy usage will require the development of novel, abundant, nontoxic energy conversion materials. Here, a cost-efficient and scalable continuous flow synthesis of Cs3Cu2I5 nanocrystals is developed as a basis for the rapid advancement of novel nanomaterials. Ideal precursor solutions are obtained through a novel batch synthesis, whose product served as a benchmark for the subsequent flow synthesis. Realizing this setup enabled a reproducible fabrication of Cs3Cu2I5 nanocrystals. The effect of volumetric flow rate and temperature on the final product's morphology and optical properties are determined, obtaining 21% quantum yield with the optimal configuration. Consequently, the size and morphology of the nanocrystals can be tuned with far more precision and in a much broader range than previously achievable. The flow setup is readily applicable to other relevant nanomaterials. It should enable a rapid determination of a material's potential and subsequently optimize its desired properties for renewable energy generation or efficient optoelectronics.

Synergistic Bactericidal Effect of Zn2+ Ions and Reactive Oxygen Species Generated in Response to Either UV or X-ray Irradiation of Zn-Doped Plasma Electrolytic Oxidation TiO2 Coatings.

Zn-containing TiO2-based coatings with Na, Ca, Si, and K additives were obtained by plasma electrolytic oxidation (PEO) of Ti in order to achieve an effective and broad bactericidal protection without compromising biocompatibility. A protocol has been developed for cleaning the coating surface from electrolyte residues, ensuring the preservation of the microstructure and composition of the surface layer. Using high-resolution transmission electron microscopy, three characteristic microstructural zones in the PEO-Zn coating are well documented: zone 1 with a TiO2-based nanocrystalline structure, zone 2 with an amorphous structure, and zone 3 around pores with an amorphous-nanocrystalline structure. The excellent cytocompatibility of PEO-Zn samples was confirmed by three different methods: monitoring the proliferation of MC3T3-E1 cells, assessing the viability of sheep osteoblast cells using calcein-AM staining and fluorescence microscopy, and incubation with spheroids based on primary osteoblast cells and mouse embryonic fibroblast NIH3T3 cells. The PEO-Zn coatings absorb >60% of the incident light over the UV and Vis-NIR spectral ranges. After 24 h, the PEO-Zn coatings completely inactivate four types of strains: Gram-positive Staphylococcus aureus CSA154 and ATCC29213 and Gram-negative Escherichia coli K261 and U20, and also prevent E. coli U20 and K261 biofilm formation. The superior antibacterial activity is associated with the synergistic effect of Zn2+ ions in safe concentration and reactive oxygen species (ROS) generated in response to either UV irradiation or soft short-term X-ray irradiation. The X-ray irradiation-induced ROS formation by a PEO coating is reported for the first time. The enhanced bactericidal activity after X-ray irradiation compared to UV illumination is attributed to the more intense ROS generation in the first few hours. The results obtained significantly expand the possibilities of using PEO coatings on the surfaces of titanium implants.

Palearctic flea beetle and pest of hops and Cannabis, Psylliodesattenuata (Coleoptera, Chrysomelidae, Galerucinae), new to North America.

Background: The univoltine leaf beetle Psylliodesattenuata (Koch, 1803) is a pest of Cannabis and Humulus (Cannabaceae) and native to the Palaearctic Region, known from eastern Asia to western Europe. New information: First North American records are presented for P.attenuata from Canada: Ontario and Québec. Adult beetle feeding damage to hops Humuluslupulus L. (Cannabacaea) plants is recorded from Québec. Diagnostic information is presented to distinguish P.attenuata from other North American Chrysomelidae and a preliminary assessment of its potential to spread in North America is presented. While our climate analysis is limited by a lack of data, it appears P.attenuata is physiologically capable of persisting throughout the range of Humulus in North America.The United States of America and Canada are now known to be home to 71 or more species of adventive Chrysomelidae.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.

The classification of hiatal shapes and their use as a marker for complexity, operative interventions, and recurrence.

BACKGROUND: Diaphragmatic reconstruction is a vital, but challenging component of hiatal hernia and antireflux surgery. Results are optimized by minimizing axial tension along the esophagus, assessed with intra-abdominal length, and radial tension across the hiatus, which has not been standardized. We categorized hiatal openings into 4 shapes, as a surrogate for radial tension, to correlate their association with operative interventions and recurrence. METHODS: We retrospectively reviewed all primary hiatal hernias (≥3 cm) repaired at a single center between 2010 and 2020. Patients with intraoperative hiatal photos with at least 1 year of follow-up were included. The hiatal openings were classified into 4 shapes: slit, inverted teardrop, "D," and oval, and ordered in this manner of hypothesized increased complexity and tension. RESULTS: A total of 239 patients were studied, with 113 (47%) having a recurrence. Age (P < .001), proportion of paraesophageal hernias (P < .001), hernia axial length (P < .001), and hiatal width (P < .001) all increased as shape progressed from slit to inverted teardrop to "D" to oval. Mesh (P = .003) and relaxing incisions (P < .001) were more commonly employed in more advanced shapes, "D" and ovals. However, recurrence (P = .88) did not correlate with hiatal shape. CONCLUSION: Four different hiatal shapes are commonly seen during hernia repair. These shapes represent a spectrum of hernia chronicity and complexity necessitating increased use of operative measures but not correlating with recurrence. Despite failing to be a direct marker for recurrence risk, hiatal shape may serve as an intraoperative tool to inform surgeons of the potential need for additional hiatal interventions.