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38096389

[Questionnaire survey of patients of medical dental organizations in different regions of the Russian Federation on the issues of individual and professional oral hygiene].

To analyze the respondents' attitudes to oral hygiene and to assess the need for professional oral hygiene in different regions of the Russian Federation based on the data of questionnaire analysis.

38096390

[The spread of aerosols and splashes during the removal of dental deposits with an ultrasonic scaler].

There is an increased prevalence of respiratory infections among dentists, which is associated with a heavily polluted breathing area in the dental office. Patients and dentists are at high risk of cross-infection due to the spread of aerosols in the form of droplets suspended in the air. The ultrasonic scaler is the largest source of aerosols and spatter in the dental office. Aerosols remain in the air for a long time even after the completion of a dental procedure and have a potential risk of inhalation.

38096391

[Assessment of microhaemodynamics and oxygenation in tissues after the vestibuloplasty with the use of a free dermal autograft in patients after the reconstructive jaw surgery with the use of the revascularized autografts].

Purpose of the study: to study the features of microhaemodynamics and oxygenation in soft tissues in the area of the plastically reconstructed jaw after the vestibuloplasty.

38096392

[Functional and aesthetic significance of the uvula in cleft palate repair].

To investigate functional and aesthetic role of uvula in cleft palate repair.

38096393

[Duration of splint therapy in patients with temporomandibular joint disorders].

Studying the duration of treatment in patients with temporomandibular joint pain dysfunction syndrome, and the relationship of the duration of treatment with the age of the patient at the beginning of therapy.

38096395

[Measuring methods of volumetric changes of soft tissues at dental implants site and tooth recessions site].

The article is a review of literature on various methods for measuring gingival thickness at implant site and tooth recession. The purpose of the study was to analyze existing methods for assessing volumetric changes in soft tissues based on literature data and give recommendations on the choice of methods. The authors analyzed available methods and identified limitations and recommendations for the use of different methods. The literature review is also helpful to identify promising methods for assessing changes in soft tissue volume, which may help authors of future studies with method selection.

38096394

[Ultrasound anatomy of masticatory muscles. (Experimental and clinical study)].

To describe the ultrasound anatomy of the masticatory muscles based on a comparison of the results of macroscopic and ultrasound studies of the masticatory muscles in vitro.

38096397

[The use of modern dressings after complex treatment of malignant tumors of the maxillofacial region].

The number of patients with malignant tumors of the head and neck is constantly growing. However, after a favorable outcome of complex treatment patients may experience adverse consequences. Surgeon should understand conditions of surrounding tissues that have undergone radiation therapy. It is necessary for special management because regenerative potential of postoperative wounds decreased. The search and development of effective wound dressings are aimed at reducing the risks of postoperative complications and improving the quality of life of this group of patients.

38096396

[Models of bone defects in rabbits used to evaluate the bone graft materials efficacy].

The review deals with the main types of experimental models of bone defects of the skull in rabbits. The information about the types of critical defects, methods of their modeling and the possibilities of application of the described models in the studies of bone graft materials in dentistry and maxillofacial surgery is systematized.

38096398

[Post-Covid osteomyelitis of the facial bones].

The pandemic of coronavirus infection existed from 2019 to 2023. The World Health Organization (WHO) has announced on May 5, 2023 that the pandemic had ended. However, it does not cease to have an adverse effect on the health of the world population. Necrotic lesions of the bones of the facial skeleton are now a characteristic sign of a severe coronavirus infection. We conducted a review of scientific publications that reflected the relationship between coronavirus and necrotic processes of the skull bones, methods of treatment, prevention and the latest developments in this direction. The purpose of this article is to review existing studies on Post-Covid osteomyelitis of facial bones, its impact, features of the clinical picture of this disease, analysis of methods and means of treatment of this group of patients. Analysis of literature data has shown that the search for an ideal dressing material continues, especially the developments of native developers stand emphasized. The advantages of modern materials over traditional ones have become unquestionable, but further research in this direction is required.

38096399

Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified MSCs or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process was demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nano-star loaded with triamcinolone are conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nano-star significantly elevate the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, was downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell was inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nano-star promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain and improve general locomotor activity, and more importantly, induced cartilage regeneration even for severe stages of arthritis model. This article is protected by copyright. All rights reserved.

38096400

Probing Spin-Dependent Ballistic Charge Transport at Single-Nanometer Length Scales.

The coherent transport of charge and spin is a key requirement of future devices for quantum computing and communication. Scattering at defects or impurities may significantly reduce the coherence of quantum-mechanical states, thereby affecting the device functionality. While numerous methods exist to experimentally assess charge transport, the real-space detection of a material's ballistic spin transport properties with nanometer resolution remains a challenge. Here we report on a novel approach that utilizes a combination of spin-polarized scanning tunneling microscopy (SP-STM) and the recently introduced molecular nanoprobe (MONA) technique. It relies on the local injection of spin-polarized charge carriers from a magnetic STM tip and their detection by a single surface-deposited phthalocyanine molecule via reversible electron-induced tautomerization events. Based on the particular electronic structure of the Rashba alloy BiAg₂, which is governed by a spin-momentum-locked surface state, we prove that the current direction inverses upon tip magnetization reversal.

38096401

Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts.

Repeated blast-traumatic brain injury (blast-TBI) has been hypothesized to cause persistent and unusual neurological and psychiatric symptoms in service members returning from war zones. Blast-wave primary effects have been supposed to induce damage and molecular alterations in the brain. However, the mechanisms through which the primary effect of an explosive-driven blast wave generate brain lesions and induce brain consequences are incompletely known. Prior findings from rat brains exposed to two consecutive explosive-driven blasts showed molecular changes (hyperphosphorylated-Tau, AQP4, S100β, PDGF, and DNA-polymerase-β) that varied in magnitude and direction across different brain regions. We aimed to compare, in an unbiased manner, the proteomic profile in the hippocampus of double blast vs sham rats using mass spectrometry (MS). Data showed differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs sham rats. Tandem mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before in blast studies, such as increases in MAGI3, a scaffolding protein at cell-cell junctions, which were confirmed by Western blotting analyses. Due to the absence of behavioral and obvious histopathological changes as described in our previous publications, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the hippocampus of rats repeatedly expsosed to blast waves generated by explosive-driven detonations.

38096402

Efficacy and Safety of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease.

Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1 developed as treatment for inflammatory bowel disease.

38096403

When Who Matters: Interviewer Effects and Survey Modality.

When and how to survey potential respondents is often determined by budgetary and external constraints, but choice of survey modality may have enormous implications for data quality. Different survey modalities may be differentially susceptible to measurement error attributable to interviewer assignment, known as interviewer effects. In this paper, we leverage highly similar surveys, one conducted face-to-face (FTF) and the other via phone, to examine variation in interviewer effects across survey modality and question type. We find that while there are no cross-modality differences for simple questions, interviewer effects are markedly higher for sensitive questions asked over the phone. These findings are likely explained by the enhanced ability of in-person interviewers to foster rapport and engagement with respondents. We conclude with a thought experiment that illustrates the potential implications for power calculations, namely, that using FTF data to inform phone surveys may substantially underestimate the necessary sample size for sensitive questions.

38096404

Pediatric Posterior Infectious Uveitis.

To describe the most important cause of infectious posterior uveitis in pediatric patients.

38096405

Disease of the Year for 2023: Pediatric Uveitis.

38096407

A cGAL-UAS bipartite expression toolkit for <i>Caenorhabditis elegans</i> sensory neurons.

Animals integrate sensory information from the environment and display various behaviors in response to external stimuli. In <i>Caenorhabditis elegans</i> hermaphrodites, 33 types of sensory neurons are responsible for chemosensation, olfaction, and mechanosensation. However, the functional roles of all sensory neurons have not been systematically studied due to the lack of facile genetic accessibility. A bipartite cGAL-UAS system has been previously developed to study tissue- or cell-specific functions in <i>C. elegans</i>. Here, we report a toolkit of new cGAL drivers that can facilitate the analysis of a vast majority of the 60 sensory neurons in <i>C. elegans</i> hermaphrodites. We generated 37 sensory neuronal cGAL drivers that drive cGAL expression by cell-specific regulatory sequences or intersection of two distinct regulatory regions with overlapping expression (split cGAL). Most cGAL-drivers exhibit expression in single types of cells. We also constructed 28 UAS effectors that allow expression of proteins to perturb or interrogate sensory neurons of choice. This cGAL-UAS sensory neuron toolkit provides a genetic platform to systematically study the functions of <i>C. elegans</i> sensory neurons.

38096408

Tradeoffs in bacterial physiology determine the efficiency of antibiotic killing.

Antibiotic effectiveness depends on a variety of factors. While many mechanistic details of antibiotic action are known, the connection between death rate and bacterial physiology is poorly understood. A common observation is that death rate in antibiotics rises linearly with growth rate; however, it remains unclear how other factors, such as environmental conditions and whole-cell physiological properties, affect bactericidal activity. To address this, we developed a high-throughput assay to precisely measure antibiotic-mediated death. We found that death rate is linear in growth rate, but the slope depends on environmental conditions. Growth under stress lowers death rate compared to nonstressed environments with similar growth rate. To understand stress's role, we developed a mathematical model of bacterial death based on resource allocation that includes a stress-response sector; we identify this sector using RNA-seq. Our model accurately predicts the minimal inhibitory concentration (MIC) with zero free parameters across a wide range of growth conditions. The model also quantitatively predicts death and MIC when sectors are experimentally modulated using cyclic adenosine monophosphate (cAMP), including protection from death at very low cAMP levels. The present study shows that different conditions with equal growth rate can have different death rates and establishes a quantitative relation between growth, death, and MIC that suggests approaches to improve antibiotic efficacy.

38096409

Master regulators of biological systems in higher dimensions.

A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. We then generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., the <i>rbs</i> locus and <i>pykF</i>) and species (e.g., <i>Lactobacilli</i>) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions.

38096410

Neuromuscular basis of <i>Drosophila</i> larval rolling escape behavior.

When threatened by dangerous or harmful stimuli, animals engage in diverse forms of rapid escape behaviors. In <i>Drosophila</i> larvae, one type of escape response involves C-shaped bending and lateral rolling followed by rapid forward crawling. The sensory circuitry that promotes larval escape has been extensively characterized; however, the motor programs underlying rolling are unknown. Here, we characterize the neuromuscular basis of rolling escape behavior. We used high-speed, volumetric, Swept Confocally Aligned Planar Excitation (SCAPE) microscopy to image muscle activity during larval rolling. Unlike sequential peristaltic muscle contractions that progress from segment to segment during forward and backward crawling, muscle activity progresses circumferentially during bending and rolling escape behavior. We propose that progression of muscular contraction around the larva's circumference results in a transient misalignment between weight and the ground support forces, which generates a torque that induces stabilizing body rotation. Therefore, successive cycles of slight misalignment followed by reactive aligning rotation lead to continuous rolling motion. Supporting our biomechanical model, we found that disrupting the activity of muscle groups undergoing circumferential contraction progression leads to rolling defects. We use EM connectome data to identify premotor to motor connectivity patterns that could drive rolling behavior and perform neural silencing approaches to demonstrate the crucial role of a group of glutamatergic premotor neurons in rolling. Our data reveal body-wide muscle activity patterns and putative premotor circuit organization for execution of the rolling escape response.

38096411

<i>GRASSY TILLERS1</i> (<i>GT1</i>) and <i>SIX-ROWED SPIKE1</i> (<i>VRS1</i>) homologs share conserved roles in growth repression.

Crop engineering and de novo domestication using gene editing are new frontiers in agriculture. However, outside of well-studied crops and model systems, prioritizing engineering targets remains challenging. Evolution can guide us, revealing genes with deeply conserved roles that have repeatedly been selected in the evolution of plant form. Homologs of the transcription factor genes <i>GRASSY TILLERS1</i> (<i>GT1</i>) and <i>SIX-ROWED SPIKE1</i> (<i>VRS1</i>) have repeatedly been targets of selection in domestication and evolution, where they repress growth in many developmental contexts. This suggests a conserved role for these genes in regulating growth repression. To test this, we determined the roles of <i>GT1</i> and <i>VRS1</i> homologs in maize (<i>Zea mays</i>) and the distantly related grass brachypodium (<i>Brachypodium distachyon</i>) using gene editing and mutant analysis. In maize, <i>gt1; vrs1-like1</i> (<i>vrl1</i>) mutants have derepressed growth of floral organs. In addition, <i>gt1; vrl1</i> mutants bore more ears and more branches, indicating broad roles in growth repression. In brachypodium, <i>Bdgt1; <i>B</i>dvrl1</i> mutants have more branches, spikelets, and flowers than wild-type plants, indicating conserved roles for <i>GT1</i> and <i>VRS1</i> homologs in growth suppression over <i>ca.</i> 59 My of grass evolution. Importantly, many of these traits influence crop productivity. Notably, maize <i>GT1</i> can suppress growth in arabidopsis (<i>Arabidopsis thaliana</i>) floral organs, despite <i>ca</i>. 160 My of evolution separating the grasses and arabidopsis. Thus, <i>GT1</i> and <i>VRS1</i> maintain their potency as growth regulators across vast timescales and in distinct developmental contexts. This work highlights the power of evolution to inform gene editing in crop improvement.

38096412

Genetic and immune determinants of <i>E. coli</i> liver abscess formation.

Systemic infections can yield distinct outcomes in different tissues. In mice, intravenous inoculation of <i>Escherichia</i> <i>coli</i> leads to bacterial replication within liver abscesses, while other organs such as the spleen clear the pathogen. Abscesses are macroscopic necrotic regions that comprise the vast majority of the bacterial burden in the animal, yet little is known about the processes underlying their formation. Here, we characterize <i>E. coli</i> liver abscesses and identify host determinants of abscess susceptibility. Spatial transcriptomics revealed that liver abscesses are associated with heterogenous immune cell clusters comprised of macrophages, neutrophils, dendritic cells, innate lymphoid cells, and T-cells that surround necrotic regions of the liver. Abscess susceptibility is heightened in the C57BL lineage, particularly in C57BL/6N females. Backcross analyses demonstrated that abscess susceptibility is a polygenic trait inherited in a sex-dependent manner without direct linkage to sex chromosomes. As early as 1 d post infection, the magnitude of <i>E. coli</i> replication in the liver distinguishes abscess-susceptible and abscess-resistant strains of mice, suggesting that the immune pathways that regulate abscess formation are induced within hours. We characterized the early hepatic response with single-cell RNA sequencing and found that mice with reduced activation of early inflammatory responses, such as those lacking the LPS receptor TLR4 (Toll-like receptor 4), are resistant to abscess formation. Experiments with barcoded <i>E. coli</i> revealed that TLR4 mediates a tradeoff between abscess formation and bacterial clearance. Together, our findings define hallmarks of <i>E. coli</i> liver abscess formation and suggest that hyperactivation of the hepatic innate immune response drives liver abscess susceptibility.

38096413

The V-type H⁺-ATPase is targeted in antidiuretic hormone control of the Malpighian "renal" tubules.

Like other insects, secretion by mosquito Malpighian tubules (MTs) is driven by the V-type H⁺-ATPase (VA) localized in the apical membrane of principal cells. In <i>Aedes aegypti</i>, the antidiuretic neurohormone CAPA inhibits secretion by MTs stimulated by select diuretic hormones; however, the cellular effectors of this inhibitory signaling cascade remain unclear. Herein, we demonstrate that the VA inhibitor bafilomycin selectively inhibits serotonin (5HT)- and calcitonin-related diuretic hormone (DH₃₁)-stimulated secretion. VA activity increases in DH₃₁-treated MTs, whereas CAPA abolishes this increase through a NOS/cGMP/PKG signaling pathway. A critical feature of VA activation involves the reversible association of the cytosolic (V₁) and membrane (V_o) complexes. Indeed, higher V₁ protein abundance was found in membrane fractions of DH₃₁-treated MTs, whereas CAPA significantly decreased V₁ abundance in membrane fractions while increasing it in cytosolic fractions. V₁ immunolocalization was observed strictly in the apical membrane of DH₃₁-treated MTs, whereas immunoreactivity was dispersed following CAPA treatment. VA complexes colocalized apically in female MTs shortly after a blood meal consistent with the peak and postpeak phases of diuresis. Comparatively, V₁ immunoreactivity in MTs was more dispersed and did not colocalize with the V_o complex in the apical membrane at 3 h post blood meal, representing a time point after the late phase of diuresis has concluded. Therefore, CAPA inhibition of MTs involves reducing VA activity and promotes complex dissociation hindering secretion. Collectively, these findings reveal a key target in hormone-mediated inhibition of MTs countering diuresis that provides a deeper understanding of this critical physiological process necessary for hydromineral balance.

38096414

Self-similarity and vanishing diffusion in fluvial landscapes.

Complex topographies exhibit universal properties when fluvial erosion dominates landscape evolution over other geomorphological processes. Similarly, we show that the solutions of a minimalist landscape evolution model display invariant behavior as the impact of soil diffusion diminishes compared to fluvial erosion at the landscape scale, yielding complete self-similarity with respect to a dimensionless channelization index. Approaching its zero limit, soil diffusion becomes confined to a region of vanishing area and large concavity or convexity, corresponding to the locus of the ridge and valley network. We demonstrate these results using one dimensional analytical solutions and two dimensional numerical simulations, supported by real-world topographic observations. Our findings on the landscape self-similarity and the localized diffusion resemble the self-similarity of turbulent flows and the role of viscous dissipation. Topographic singularities in the vanishing diffusion limit are suggestive of shock waves and singularities observed in nonlinear complex systems.

38096415

Heteromultimeric sarbecovirus receptor binding domain immunogens primarily generate variant-specific neutralizing antibodies.

Vaccination will likely be a key component of strategies to curtail or prevent future sarbecovirus pandemics and to reduce the prevalence of infection and disease by future SARS-CoV-2 variants. A "pan-sarbecovirus" vaccine, that provides maximum possible mitigation of human disease, should elicit neutralizing antibodies with maximum possible breadth. By positioning multiple different receptor binding domain (RBD) antigens in close proximity on a single immunogen, it is postulated that cross-reactive B cell receptors might be selectively engaged. Heteromultimeric vaccines could therefore elicit individual antibodies that neutralize a broad range of viral species. Here, we use model systems to investigate the ability of multimeric sarbecovirus RBD immunogens to expand cross-reactive B cells and elicit broadly reactive antibodies. Homomultimeric RBD immunogens generated higher serum neutralizing antibody titers than the equivalent monomeric immunogens, while heteromultimeric RBD immunogens generated neutralizing antibodies recognizing each RBD component. Moreover, RBD heterodimers elicited a greater fraction of cross-reactive germinal center B cells and cross-reactive RBD binding antibodies than did homodimers. However, when serum antibodies from RBD heterodimer-immunized mice were depleted using one RBD component, neutralization activity against the homologous viral pseudotype was removed, but neutralization activity against pseudotypes corresponding to the other RBD component was unaffected. Overall, simply combining divergent RBDs in a single immunogen generates largely separate sets of individual RBD-specific neutralizing serum antibodies that are mostly incapable of neutralizing viruses that diverge from the immunogen components.

38096416

The primacy of temporal dynamics in driving spatial self-organization of soil iron redox patterns.

This study investigates mechanisms that generate regularly spaced iron-rich bands in upland soils. These striking features appear in soils worldwide, but beyond a generalized association with changing redox, their genesis is yet to be explained. Upland soils exhibit significant redox fluctuations driven by rainfall, groundwater changes, or irrigation. Pattern formation in such systems provides an opportunity to investigate the temporal aspects of spatial self-organization, which have been heretofore understudied. By comparing multiple alternative mechanisms, we found that regular iron banding in upland soils is explained by coupling two sets of scale-dependent feedbacks, the general principle of Turing morphogenesis. First, clay dispersion and coagulation in iron redox fluctuations amplify soil Fe(III) aggregation and crystal growth to a level that negatively affects root growth. Second, the activation of this negative root response to highly crystalline Fe(III) leads to the formation of rhythmic iron bands. In forming iron bands, environmental variability plays a critical role. It creates alternating anoxic and oxic conditions for required pattern-forming processes to occur in distinctly separated times and determines durations of anoxic and oxic episodes, thereby controlling relative rates of processes accompanying oxidation and reduction reactions. As Turing morphogenesis requires ratios of certain process rates to be within a specific range, environmental variability thus modifies the likelihood that pattern formation will occur. Projected changes of climatic regime could significantly alter many spatially self-organized systems, as well as the ecological functioning associated with the striking patterns they present. This temporal dimension of pattern formation merits close attention in the future.

38096417

Antimicrobial resistance level and conjugation permissiveness shape plasmid distribution in clinical enterobacteria.

Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR plasmids are widespread in clinical settings, but their distribution is not random, and certain associations between plasmids and bacterial clones are particularly successful. For example, the globally spread carbapenem resistance plasmid pOXA-48 can use a wide range of enterobacterial species as hosts, but it is usually associated with a small number of specific <i>Klebsiella pneumoniae</i> clones. These successful associations represent an important threat for hospitalized patients. However, knowledge remains limited about the factors determining AMR plasmid distribution in clinically relevant bacteria. Here, we combined in vitro and in vivo experimental approaches to analyze pOXA-48-associated AMR levels and conjugation dynamics in a collection of wild-type enterobacterial strains isolated from hospitalized patients. Our results revealed significant variability in these traits across different bacterial hosts, with <i>Klebsiella</i> spp. strains showing higher pOXA-48-mediated AMR and conjugation frequencies than <i>Escherichia coli</i> strains. Using experimentally determined parameters, we developed a simple mathematical model to interrogate the contribution of AMR levels and conjugation permissiveness to plasmid distribution in bacterial communities. The simulations revealed that a small subset of clones, combining high AMR levels and conjugation permissiveness, play a critical role in stabilizing the plasmid in different polyclonal microbial communities. These results help to explain the preferential association of plasmid pOXA-48 with <i>K. pneumoniae</i> clones in clinical settings. More generally, our study reveals that species- and strain-specific variability in plasmid-associated phenotypes shape AMR evolution in clinically relevant bacterial communities.

38096418

Batteryless implantable device with built-in mechanical clock for automated and precisely timed drug administration.

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration.

38096419

Correction for Cao et al., Salinity-mediated water self-purification via bond network distorting of H₂O molecules on DRC-surface.

38096420

An observed population of intermediate-mass helium stars that have been stripped in binaries.

The hydrogen-rich outer layers of massive stars can be removed by interactions with a binary companion. Theoretical models predict that this stripping produces a population of hot helium stars of ~2 to 8 solar masses (<i>M</i>_&#9737;), however, only one such system has been identified thus far. We used ultraviolet photometry to identify potential stripped helium stars then investigated 25 of them using optical spectroscopy. We identified stars with high temperatures (~60,000 to 100,000 kelvin), high surface gravities, and hydrogen-depleted surfaces; 16 stars also showed binary motion. These properties match expectations for stars with initial masses of 8 to 25 <i>M</i>_&#9737; that were stripped by binary interaction. Their masses fall in the gap between subdwarf helium stars and Wolf-Rayet stars. We propose that these stars could be progenitors of stripped-envelope supernovae.

38096421

Ultrafast and Broad-Band Graphene Heterojunction Photodetectors with High Gain.

Graphene possesses an exotic band structure that spans a wide range of important technological wavelength regimes for photodetection, all within a single material. Conventional methods aimed at enhancing detection efficiency often suffer from an extended response time when the light is switched off. The task of achieving ultrafast broad-band photodetection with a high gain remains challenging. Here, we propose a devised architecture that combines graphene with a photosensitizer composed of an alternating strip superstructure of WS₂-WSe₂. Upon illumination, n⁺-WS₂ and p⁺-WSe₂ strips create alternating electron- and hole-conduction channels in graphene, effectively overcoming the tradeoff between the responsivity and switch time. This configuration allows for achieving a responsivity of 1.7 &#215; 10⁷ mA/W, with an extrinsic response time of 3-4 &#956;s. The inclusion of the superstructure booster enables photodetection across a wide range from the near-ultraviolet to mid-infrared regime and offers a distinctive photogating route for high responsivity and fast temporal response in the pursuit of broad-band detection.

38096422

Ultrasound-Induced Cascade Amplification in a Mechanoluminescent Nanotransducer for Enhanced Sono-Optogenetic Deep Brain Stimulation.

Remote and genetically targeted neuromodulation in the deep brain is important for understanding and treatment of neurological diseases. Ultrasound-triggered mechanoluminescent technology offers a promising approach for achieving remote and genetically targeted brain modulation. However, its application has thus far been limited to shallow brain depths due to challenges related to low sonochemical reaction efficiency and restricted photon yields. Here we report a cascaded mechanoluminescent nanotransducer to achieve efficient light emission upon ultrasound stimulation. As a result, blue light was generated under ultrasound stimulation with a subsecond response latency. Leveraging the high energy transfer efficiency of focused ultrasound in brain tissue and the high sensitivity to ultrasound of these mechanoluminescent nanotransducers, we are able to show efficient photon delivery and activation of ChR2-expressing neurons in both the superficial motor cortex and deep ventral tegmental area after intracranial injection. Our liposome nanotransducers enable minimally invasive deep brain stimulation for behavioral control in animals via a flexible, mechanoluminescent sono-optogenetic system.

38096423

Microarray-Based CD38 Peptide Probe Screening for Multiple Myeloma Imaging.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 10⁵ peptide library with a dissociation constant (<i>K</i>_D) of 10^-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and ⁶⁸Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

38096424

Engineering of a Self-Regulatory Bidirectional DNA Assembly Circuit for Amplified MicroRNA Imaging.

The engineering of catalytic hybridization DNA circuits represents versatile ways to orchestrate a complex flux of molecular information at the nanoscale, with potential applications in DNA-encoded biosensing, drug discovery, and therapeutics. However, the diffusive escape of intermediates and unintentional binding interactions remain an unsolved challenge. Herein, we developed a compact, yet efficient, self-regulatory assembly circuit (SAC) for achieving robust microRNA (miRNA) imaging in live cells through DNA-templated guaranteed catalytic hybridization. By integrating the toehold strand with a preblocked palindromic fragment in the stem domain, the proposed miniature SAC system allows the reactant-to-template-controlled proximal hybridization, thus facilitating the bidirectional-sustained assembly and the localization-intensified signal amplification without undesired crosstalk. With condensed components and low reactant complexity, the SAC amplifier realized high-contrast intracellular miRNA imaging. We anticipate that this simple and template-controlled design can enrich the clinical diagnosis and prognosis toolbox.

38096425

Cytoplasmic Accumulation and Permeability of Antibiotics in Gram Positive and Gram Negative Bacteria Visualized in Real-Time via a Fluorogenic Tagging Strategy.

In this study, we describe the first real-time live cell assay for compound accumulation and permeability in both Gram positive and Gram negative bacteria. The assay utilizes a novel fluorogenic tagging strategy that permits direct visualization of compound accumulation dynamics in the cytoplasm of live cells, unobscured by washing or other processing steps. Quantitative differences could be reproducibly measured by flow cytometry at compound concentrations below the limit of detection for MS-based approaches. We establish the fluorogenic assay in <i>E. coli</i> and <i>B. subtilis</i> and compare the intracellular accumulation of two antibiotics, ciprofloxacin and ampicillin, with related pharmacophores in these bacteria.

38096426

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective.

Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.

38096427

Graphene-Based Nanomaterials and Their Interactions with Lipid Membranes.

Graphene-based nanomaterials (GNMs) have captured increasing attention in the recent advancement of materials science and nanotechnology owing to their excellent physicochemical properties. Despite having unquestionable advances, the application of GNMs in biological and medical sciences is still limited due to the lack of knowledge and precise control over their interaction with the biological milieu. The cellular membrane is the first barrier with which GNMs interact before entering a cell. Therefore, understanding how they interact with cell membranes is important from the perspective of safe use in biological and biomedical fields. In this review, we systematically summarize the recent efforts in predicting the interactions between GNMs and model cellular membranes. This review provides insights into how GNMs interact with lipid membranes and self-assemble in and around them. Both the computational simulations and experimental observations are summarized. The interactions are classified depending on the physicochemical properties (structure, chemistry, and orientation) of GNMs and various model membranes. The thermodynamic parameters, structural details, and supramolecular forces are listed to understand the interactions which would help circumvent potential risks and provide guidance for safe use in the future. At the end of this review, future prospective and emerging challenges in this research field are discussed.

38096428

Direct Fabrication of PET-Based Thermotolerant Separators for Lithium-Ion Batteries with Ion Irradiation Technology.

Lithium-ion batteries (LIBs) play a pivotal role as essential components in various applications, including mobile devices, energy storage power supplies, and electric vehicles. The widespread utilization of LIBs underscores their significance in the field of energy storage. High-performance LIBs should exhibit two key characteristics that have been persistently sought: high energy density and safety. The separator, a critical part of LIBs, is of paramount importance in ensuring battery safety, thus requiring its high thermal stability and uniform nanochannels. Here, the novel ion-track etched polyethylene terephthalate (ITE PET) separator is controllably fabricated with ion irradiation technology. Unlike conventional polypropylene (PP) separators, the ITE PET separator demonstrated vertically aligned nanochannels with uniform channel size and distribution. The remarkable characteristics of the ITE PET separator include not only high electrolyte wettability but also exceptional thermal stability, capable of withstanding temperatures as high as 180 °C. Furthermore, the ITE PET separator exhibits a higher lithium-ion transfer number (0.59), which is advantageous in enhancing battery performance. The structural and inherent advantages of ITE PET separators contribute to enhance the C-rate capacity, electrochemical, and long-term cycling (300 cycles) stability observed in the corresponding batteries. The newly developed method for fabricating ITE PET separators, which possess high thermal stability and a uniform channel structure, fulfills the demand for high-temperature-resistant separators without requiring any modification procedures. Moreover, this method can be easily scaled up using simple processes, making it a competitive strategy for producing thermotolerant separators.

38096429

Nickel-Catalyzed Reductive Arylation of α-Bromo Sulfoxide.

A nickel-catalyzed cross-electrophile coupling of aryl iodides with α-bromo sulfoxide to access a diverse array of aryl benzyl sulfoxides has been discovered. These reactions occurred under mild conditions with excellent functional group tolerance so that optically enriched sulfoxides could be coupled with aryl iodides, generating corresponding sulfoxides with excellent stereochemical integrity. Furthermore, the scalability of this transformation was demonstrated. Initial mechanistic studies revealed that the reaction undergoes a radical pathway.

38096431

A Feasibility Study to Test the NICU Paternal Needs Inventory.

There has been little research exploring paternal needs while experiencing a neonatal intensive care unit (NICU) stay. Some tools exist to measure paternal needs, but do not incorporate items to capture important information about how fathers cope with stress differently, and may have different needs. Therefore, an instrument is needed to measure and prioritize what needs are important to fathers to help facilitate the development of nursing interventions to help fathers cope with the NICU environment.

38096430

Influence of Interaction between Electrolyte with Side-Chain Free Conjugated Polymer on the Performance of Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) offer significant advantages in electrophysiological applications, primarily due to their ability to facilitate ionic-to-electronic conversion and establish a direct interface with the surrounding aqueous environments by using organic mixed ionic-electronic conductors. This study employs a side-chain free n-type conducting polymer, poly(benzodifurandione) (PBFDO), as the channel material in OECTs to scrutinize the interplay between various ion concentrations in electrolytes and the conjugated polymer and to assess their subsequent impact on device performance. Our findings reveal that PBFDO-based OECTs demonstrate superior transfer characteristics, attributed to their high conductivity and remarkable stability in aqueous solutions. Interestingly, the ion concentration does not alter the electronic band structure of PBFDO during the doping process, but a high-salt-concentration electrolyte could accelerate the electrochemical process compared to its counterparts. Furthermore, the diluted solution significantly enhances the surface roughness and decreases the crystalline coherence length of the film compared with concentrated solutions. A quantitative analysis utilizing an electrochemical quartz crystal microbalance discloses that the electrolyte ions penetrate the PBFDO film, inducing the absorption of a fraction of water molecules, which is pronounced in diluted solutions and negligible in their concentrated counterparts. This notable swelling of the polymer in diluted solutions potentially hampers the transport of charge carriers, consequently diminishing the OECT performance. This research elucidates a direct correlation between microstructure alterations and device performance during operation, paving the way for the optimization of ionic and electronic conductivity in polymers to foster the development of high-performance organic electronic devices.

38096432

Public health vandalism: new Government scraps world-leading smokefree legislation.

38096433

Audit of antimicrobial stewardship in medical inpatients in Waikato, New Zealand 2021.

Given the threat of rising antimicrobial resistance (AMR), 10 audit standards were selected to audit antimicrobial stewardship (AMS) in secondary care to assess guideline adherence and establish quality improvement initiatives in antimicrobial prescribing.

38096434

Considerations in the assessment and management of ADHD within the TGDNB population.

In this article we consider current literature around Attention Deficit Hyperactivity Disorder (ADHD) in the transgender, gender diverse and non-binary (TGDNB) population.

38096435

A diabetes registrar assisted workflow intervention in general practice for systematic initiation of cardiorenal medications for patients with type 2 diabetes and albuminuria in Aotearoa New Zealand.

To evaluate whether a weekly diabetes registrar clinic and case discussions conducted over 12 weeks in primary care improves guideline management of type 2 diabetes (T2D).

38096437

Raise the Flag I: the impact of a sepsis quality improvement programme on delivery of a sepsis resuscitation bundle at a tertiary hospital in New Zealand.

To study changes in sepsis resuscitation practice at a tertiary hospital before and after the introduction of a quality improvement programme, and to identify variables associated with its delivery.

38096436

Key informant perspectives on a centralised contact tracing system for sexually transmitted infections.

To meet the demand of contact tracing requirements associated with Aotearoa New Zealand's COVID-19 pandemic response, a national contact tracing service was established. Contact tracing for sexually transmitted infections (STIs) like chlamydia, gonorrhoea and syphilis is usually done at the clinic level, and evidence suggests it is under-resourced and often incomplete.

38096438

Who Australasians trusted during COVID-19: lessons from the pandemic response.

Public trust in authoritative information sources is a key element of a successful public health response to a pandemic. This study investigated which sources of COVID-19 advice were most trusted by a primarily New Zealand-based cohort and considers implications for policy and practice regarding future pandemics.

38096439

Robot-assisted general surgery in Aotearoa New Zealand.

Robot-assisted surgery refers to a surgeon controlling a robotic device that performs an operation. This viewpoint explores the current state of robot-assisted surgery in Aotearoa New Zealand using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, California, United States), the only currently available robotic surgical system for general surgery in the country. We describe the contemporary progress in Aotearoa New Zealand compared to Australia and globally, and present emerging high-level evidence from randomised controlled trials regarding the utility of the robot-assisted approach for general surgery procedures. From the available evidence, we suggest that the value of robot-assisted general surgery in the public healthcare system arises from its emerging clinical benefits for complex procedures and its potential to engender equitable access and outcomes, particularly for Māori and Pacific peoples, improve education and training and contribute towards quality assurance and workforce development. Therefore, its implementation aligns with the New Zealand Health Strategy's long-term goals and priority areas to achieve pae ora, healthy futures for all.

38096440

A case of imported rabies in Aotearoa New Zealand.

38096441

Wireless Deep Brain Stimulation by Ultrasound-Responsive Molecular Piezoelectric Nanogenerators.

Implantable neural stimulation devices are becoming prevalent in bioelectronic medicine for the precise treatment of various clinical diseases. Nevertheless, the limited lifespan and buckling size of the implanted devices remain significant obstacles for chronic clinical application. In this study, we developed an ultrasound-driven battery-free neurostimulator based on a high-performance mini-sized nanogenerator and demonstrated its successful application for the deep-brain-stimulation (DBS) therapy of Parkinson's disease in a rat model. This soft piezoelectric-triboelectric hybrid nanogenerators (PTNG) are made of porous thin-films of molecular piezoelectric materials, which have great advantages of facile, scalable, low-temperature, and flexible processing. Without any bucky accessory control circuits, the subcutaneously implanted soft PTNG can function as a wirelessly powered neurostimulator, allowing for the adjustment of stimulation parameters through external programmable ultrasound pulses. This DBS electroceutical application of energy-harvesting thin-film devices based on molecular piezoelectric materials provides valuable insight into the development of a soft high-performance bioelectronic device.

38096443

The Emerging Science of Interacting Minds.

For over a century, psychology has focused on uncovering mental processes of a single individual. However, humans rarely navigate the world in isolation. The most important determinants of successful development, mental health, and our individual traits and preferences arise from interacting with other individuals. Social interaction underpins who we are, how we think, and how we behave. Here we discuss the key methodological challenges that have limited progress in establishing a robust science of how minds interact and the new tools that are beginning to overcome these challenges. A deep understanding of the human mind requires studying the context within which it originates and exists: social interaction.

38096442

The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy.

Label="BACKGROUND" NlmCategory="BACKGROUND">Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new technique that enables the use of alpha particles for the treatment of solid tumors. Alpha DaRT employs interstitial sources carrying a few &#956;Ci of ²²⁴ Ra below their surface, designed to release a chain of short-lived atoms (progeny of ²²⁴ Ra) which emit alpha particles, along with beta, Auger, and conversion electrons, x- and gamma rays. These atoms diffuse around the source and create-primarily through their alpha decays-a lethal high-dose region measuring a few millimeters in&#160;diameter.

38096444

Advance Care Planning Engagement Strategies for Primary Care Providers Seeing Diverse Patient Populations: A Scoping Review.

Diverse patients are less likely than Whites to have advance care planning. The primary purpose of this scoping review was to summarize recent evidence about advance care planning engagement interventions for primary care providers working with diverse patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for Scoping Reviews (PRISMA-ScR) Checklist was followed. Peer-reviewed articles published in English since 2000 reporting the results of studies testing intervention programs in primary care to improve advance care planning with adult, racially diverse populations were included. Searches were conducted in 5 online databases and yielded 72 articles. Gray literature yielded 23 articles. Two authors independently reviewed the abstracts of 72 articles determining that 9 articles met the aim of this review. These studies were analyzed by communication tools and other resources, population, intervention, primary outcomes, instruments, and primary findings and organized into 3 categories: (a) provider-focused interventions, (b) patient-focused interventions, and (c) multilevel interventions. Improvement in advance care planning outcomes can be achieved for racially diverse populations by implementing targeted advance care planning engagement interventions for both providers and patients. These interventions can be used in primary care to increase advance care planning for diverse patients. More research is needed that evaluates best practices for integrating advance care planning into primary care workflows.

38096445

Capitalizing on the Value of the Clinical Nurse Specialist in Palliative Care.

The clinical nurse specialist (CNS) is 1 of the 4 advanced practice registered nurse roles and a vital component in palliative and hospice nursing care. The CNS is a specialty expert clinician capable of practicing in a variety of health care settings including acute care, primary care, and specialty ambulatory care. The CNS integrates palliative care standards across the 3 spheres of impact (patient, nurse, and system) to improve care patients receive at end of life, mentoring and coaching nurses in the unique aspects of palliative and hospice care (HPC), and serving as a clinical expert for the organization to ensure best practices and quality outcomes. Clinical nurse specialists are trained to diagnose, treat, and prescribe to provide holistic care to their patients. However, challenges exist for the CNS role due to variations in state regulations regarding title protection and scope of practice leading to inconsistency in and misperception of the CNS role. Clinical nurse specialists have a wealth of expertise that can lead to systematic improvement in patient outcomes, advances in hospice and palliative nursing practice, and management of HPC patients and their families. Clinical nurse specialists are a hidden treasure that should be integrated into HPC practice.

38096447

Impact of Air Pollution and MUC5B Genotype on Survival in Idiopathic Pulmonary Fibrosis.

38096448

Oral prosthetic rehabilitation in patients with Epidermolysis Bullosa Hereditaria: a systematic review.

Epidermolysis bullosa hereditaria (EBH) is a group of rare diseases characterized by a cutaneous-mucosal fragility with the formation of bullae, including the oral mucosa. Therapeutic choices, especially prosthetic rehabilitation, must anticipate the worsening of the limitation of oral opening while respecting the functional and aesthetic expectations of the patients. This review on the oral prosthetic rehabilitation of patients with epidermolysis bullosa hereditaria (EBH) to study the level of evidence and quality of the presented available articles and establish clinical recommendations for the prosthetic management of these patients.

38096446

Thai Nurses' and Midwives' Perceptions Regarding Barriers, Facilitators, and Competence in Neonatal Pain Management.

Effective neonatal pain management is reliant upon the expert care of nurses and midwives working in neonatal intensive care units (NICUs). Previous research has explored barriers, facilitators, and some aspects of nurse competence in managing neonatal pain; however, this research has been predominantly performed in Western countries. To date, little is known about the barriers, facilitators, and perceived competence of Thai nurses and midwives in relation to neonatal pain management in NICUs. Exploring Thai nurses' and midwives' perceptions in these areas is crucial for understanding the contextual nuances of neonatal pain management, which can guide the provision of care for these high-risk neonates.

38096449

Older Adults' Perceptions of the Technology Influence on Interpersonal Communication: A Cross-Sectional Study.

This study aimed to understand the association between the online experience of older adults, their socio-demographic background, and their perceptions regarding the influence of the new technologies on their interpersonal communication. Technology familiarity and grey digital divide approaches served as the study's theoretical framework. The data were obtained from the 2020 Israel Social Survey and analyzed using multinomial logistic regression models. The sample included adults aged 60 years and older (<i>N</i> = 1,607). The findings show that online group participation and general Internet use, though to a varying extent, corresponded to more positive perceptions of influence of the new technologies on both family and peer communication. Female gender, tertiary education, and belonging to ethnic majority group were associated with more positive perceptions in the studied context. The results imply that online experience of older adults is more dominant than their background with respect to perceptions regarding the influence of new technologies on interpersonal communication. The findings imply that older adults should engage in various activities on the Internet, especially in the online group participation, in order to have better perceptions regarding the new technology influence on interpersonal communication.

38096451

Author Index to Volume 35.

38096450

Nurse-Led, Telephone-Based Primary Palliative Care Intervention for Patients With Lung Cancer: Domains of Quality Care.

Palliative care is traditionally delivered by specialty-trained palliative care teams. Because of a national workforce shortage of palliative care specialists, there is an urgent need to explore alternative models of palliative care delivery to meet the needs of patients living with serious illness. As part of a multisite randomized controlled trial, 2 registered nurses without previous palliative care experience were trained to deliver a primary palliative care intervention to patients with newly diagnosed lung cancer. The intervention focused on assessing and managing symptoms, psychosocial needs, education, and initiating goals-of-care discussions. The primary outcome, improved symptom burden and quality of life, was not statistically significant. Despite this finding, nurses addressed 5 of the 8 National Consensus Project Guidelines domains of quality palliative care: structure and processes of care; physical, psychological, and social aspects of care; and ethical and legal aspects. Patients' engagement in goals-of-care discussions, a measure of high-quality palliative care, increased. Clinical recommendations offered by the nurses to the patients' clinicians were addressed and accepted on a timely basis. Most patients rated satisfaction with the intervention as "very or extremely" satisfied. These findings may inform future nurse-led palliative care interventions on the specific quality domains of palliative care.

38096452

"I Want to Be Really Clear": What Male Sex Workers Want to Clarify With Prospective Clients Before Agreeing to Meet for Sex.

Men who have sex with men (MSM) and engage in sex work (MSW) frequently meet clients through dating/hookup apps. This provides an opportunity to discuss the parameters of the exchange prior to meeting and to learn things about the prospective client and the risks he might pose. Limited research has examined the specific issues or topics MSWs discuss with clients before agreeing to meet. We analyzed interview data from a sample of 180 MSWs from eight U.S. cities who engaged in exchange sex with clients they had primarily met through dating/hookup apps and websites. Participants typically asked about clients' sexual interests and expectations regarding what will transpire when they meet to make sure they were compatible with their own boundaries and limitations. Most participants inquired about clients' sexual health and often discussed condom use. Assertiveness and communication skills training might help MSWs negotiate encounters with clients that promote health and safety.

38096453

Primary Care Providers' Information Needs for Prescribing Adolescents HIV Pre-Exposure Prophylaxis.

Although knowledge is a salient determinant in primary care providers (PCPs) prescribing HIV pre-exposure prophylaxis (PrEP) to adolescents, we know little about what information PCPs want about PrEP. We conducted an online mixed-method study to explore the PrEP information needs of a national sample of 351 PCPs. We analyzed data with deductive content analysis and compared themes between respondents who were aware and not aware of PrEP, knowledgeable and not knowledgeable of the prescribing guidelines, and prescribed and never prescribed PrEP to an adolescent. PCPs who were unknowledgeable about PrEP and never prescribed PrEP to an adolescent mentioned manufacturing information, indications and dosing, and contraindications and adverse reactions more so than PCPs who were aware of and prescribed PrEP. A better understanding of the information needs of PCPs could inform provider education interventions. Future research must examine the facilitators and barriers to integrating PrEP information into medical education and clinical settings.

38096454

Exploring Individual and Contextual Factors Associated With Sexual Risk and Substance Use Among Underserved GBQMSM and Transgender and Nonbinary Persons in South Central Appalachia.

Gay, bisexual, queer, and other men who have sex with men (GBQMSM) and transgender and nonbinary persons are at elevated risk for HIV, sexually transmitted infections (STIs), and hepatitis C (HCV); in Appalachia, these communities experience more disease burden. However, little is known about the factors influencing risk. Sixteen semistructured in-depth interviews were conducted examining factors influencing prevention and care. Data were analyzed using constant comparison methodology. Fifteen themes emerged within four domains: social environment (e.g., microaggressions across gender, sexual orientation, and racial identities), substance use (e.g., high prevalence, use as coping mechanism), sexual health (e.g., misinformation and denial of risk for HIV and STIs), and access to health care (e.g., cost and transportation barriers, lack of local respectful care). Findings highlighted salient barriers and assets influencing prevention and care and suggest that multilevel interventions are needed to improve access to and use of HIV, STI, and HCV prevention and care services.

38096455

"What Is the Benefit?": Perceptions and Preferences for Long-Acting Injectable Antiretroviral Therapy Among People Living With HIV.

Long-acting injectable antiretroviral therapy (LA-ART) expands treatment options for people living with HIV (PLWH). This qualitative study characterizes LA-ART awareness, perceptions, and preferences among PLWH engaged in HIV care. From 2019 through 2021, we conducted semistructured in-depth interviews with 71 PLWH sampled from three clinics in three U.S. settings (North Carolina, Washington, DC, Massachusetts). Transcripts were analyzed using narrative and thematic techniques. Participant mean age was 46 years (range 24-72); most were cisgender men (55%) and virally suppressed (73%). Most participants had not heard of LA-ART and reacted with a mix of excitement and cautiousness. Potential LA-ART benefits included easier adherence, privacy, and effectiveness; concerns included effectiveness, side effects, costs, and increased clinic visits. Participants appreciated that LA-ART could support achieving and sustaining viral suppression. To inform their decision, participants wanted more information and convenient access and administration. Findings indicated that a shared decision-making approach and economic and logistical support for PLWH could facilitate LA-ART uptake.

38096456

<i>Infecci&#243;n de Amor</i> (Infectious Love): Development and Acceptability of a Telenovela/Soap Opera Intervention for HIV Prevention For Latinas.

Latinas continue to be disproportionately affected by HIV in the United States. Effective interventions to address HIV-related disparities among Latinas are available; however, they have not achieved widespread dissemination due to implementation challenges for real-world settings. A culturally tailored intervention that increases access to HIV prevention is urgently needed. The objective of this study was to develop a culturally tailored telenovela (i.e., a soap opera) to promote HIV prevention behaviors (condom use; HIV testing; and pre-exposure prophylaxis awareness, access, and use) among Latinas. The study was conducted in community organizations throughout South Florida. A total of 44 Spanish-speaking Latinas, 18-35 years old, and sexually active with a man in the past 6 months participated in the study. The final product was an HIV prevention telenovela that incorporated Latinas' ideas and feedback and was produced as four 10-minute filmed episodes. This study aimed to develop innovative approaches to reduce HIV-related disparities for Latinas.

38096457

Development of a Video-Delivered Serial Drama Designed to Reduce Community Homophobia and HIV Stigma, Decrease Sexual Risk Behavior, and Increase HIV Testing Among Black Youth.

This article describes the development of a video serial drama intervention that was designed to address factors that influence HIV in the United States among Black youth. These include HIV testing, sexual behaviors not protected by condoms, negative attitudes towards sexual minorities, and HIV stigma. Behavior-change principles (social learning theory and education-entertainment) and input from members of the priority audience formed the basis of this 27-episode (3 minutes each) drama for dissemination on multiple platforms, including in public spaces or privately online. The developmental process, specifically involving members of the population of interest and use of behavioral theory, enriched the narrative elements and likely ensured intervention acceptability, enhancing effectiveness. Public health practitioners and prevention programmers may want to consider using this intervention and/or the narrative communication approach when intervening to change behavior.

38096458

Exploring the Dynamics of Athletes' Enjoyment and Self-Determined Motivation, and of the Motivational Climate in Youth Football: A Longitudinal Perspective.

We aimed to explore a short period longitudinal interplay between athletes' enjoyment and their self-determined motivation and motivational climate in youth football. We recruited 109 youth football athletes (79 males, 30 females) through a convenient sampling method. We included individuals within the 12-17-year-old age range, with a mean age of 14.31 (<i>SD</i> = 1.46) years. To examine these proposed associations, we performed hierarchical multiple regression analyses and found that enjoyment at pre-season assessment (T1) and self-determined motivation and a task-involving sport climate at mid-season (T2) were significant predictors of mid-season enjoyment (at T2). However, self-determined motivation and task-involving climate at T1 did not significantly contribute to the model. These findings emphasize the importance of initial enjoyment and an evolved self-determined motivation, and task-involving climate in understanding later enjoyment in sport. Coaches, practitioners, and policymakers should prioritize strategies that enhance intrinsic motivation, provide opportunities for autonomy, and cultivate a supportive and growth-oriented environment.

38096459

Dissecting components of the <i>Campylobacter jejuni fetMP-fetABCDEF</i> gene cluster under iron limitation.

Label="IMPORTANCE" NlmCategory="OBJECTIVE"> <i>Campylobacter jejuni</i> is a bacterium that is prevalent in the ceca of farmed poultry such as chickens. Consumption of ill-prepared poultry is thus the most common route by which <i>C. jejuni</i> infects the human gut to cause a typically self-limiting but severe gastrointestinal illness that can be fatal to very young, old, or immunocompromised people. The lack of a vaccine and an increasing resistance to current antibiotics highlight a need to better understand the mechanisms that make <i>C. jejuni</i> a successful human pathogen. This study focused on the functional components of one such mechanism-a molecular system that helps <i>C. jejuni</i> thrive despite the restriction on growth-available iron by the human body, which typically defends against pathogens. In providing a deeper understanding of how this system functions, this study contributes toward the goal of reducing the enormous global socioeconomic burden caused by <i>C. jejuni</i>.

38096460

Sleep Health amongst Patients Attending Adult Neurology Clinic in Abakaliki, Nigeria.

Sleep health indicates how well an individual or population sleeps. Good sleep health is characterized by subjective satisfaction, sustained alertness during waking hours, appropriate timing, high efficiency, and adequate duration. Poor sleep health is associated with many short-term and long-term health consequences. There are limited data on the pattern of sleep health in Nigeria. Against this backdrop, we embarked on this study to determine the Pattern of Sleep Health among patients attending the Adult Neurology clinic in a Federal Teaching Hospital, in Abakaliki, Nigeria.

38096461

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial.

38096463

Cancer Research in Vulnerable Populations: A Call for Collaboration and Sustainability From MENAT Countries.

Cancer is a major burden across Middle East, North Africa, Türkiye (MENAT). Many MENAT countries experience multiple conflicts that compound vulnerabilities, but little research investigates the linkages between vulnerability and cancer research. This study examines the current level and the potential for cancer research among vulnerable populations in the MENAT region, aiming to provide direction toward developing a research agenda on the region's vulnerable populations.

38096462

Four Additional Doses of PEG-L-Asparaginase During the Consolidation Phase in the AIEOP-BFM ALL 2009 Protocol Do Not Improve Outcome and Increase Toxicity in High-Risk ALL: Results of a Randomized Study.

The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome.

38096464

Evaluating the Quality of Pain Management Satisfaction Among Oncology Patients in a Hospital Setting: Psychometric Properties of the Arabic Version of Pain Care Quality Survey.

The purpose of this mixed-methods psychometric study was to translate and adapt the Arabic Pain Care Quality (APainCQ) Survey to Arabic and to measure the quality of pain care provided to Arab patients.

38096465

Population-Level Access to Breast Cancer Early Detection and Diagnosis in Nigeria.

Mammography, breast ultrasound (US), and US-guided breast biopsy are essential services for breast cancer early detection and diagnosis. This study undertook a comprehensive evaluation to determine population-level access to these services for breast cancer early detection and diagnosis in Nigeria using a previously validated geographic information system (GIS) model.

38096466

<i>In memoriam -</i> David Ernest Minnikin (1939- 2021).

38096467

Developing the POTOMAC Model: A Novel Prediction Model to Study the Impact of Lymphopenia Kinetics on Survival Outcomes in Head and Neck Cancer Via an Ensemble Tree-Based Machine Learning Approach.

Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline versus treatment-related lymphopenia, a robust analysis is necessary to investigate the relative importance of various lymphopenia metrics (LMs) in predicting survival outcomes.

38096468

Breaking Barriers: Integrating Germline Testing With Oncology Care.

38096469

Computing the Cost of Care per Patient per Day for Patients With Metastatic Neuroendocrine Neoplasms.

Patients with well-differentiated, low-grade metastatic neuroendocrine neoplasms (NENs) usually have a long median survival and require complex, expensive care over many years at multidisciplinary centers. The cost burden for patients and institutions serves as a barrier to care. Understanding the drivers of these costs and whether intense monitoring adds value will help to optimize value-based care.

38096470

Sensitivity to ALK-Directed Therapy in Osteosarcoma With an Acquired <i>ALK</i> Rearrangement.

38096471

Treating Early and Often: Targeted Therapeutics in the Adjuvant Setting.

38096472

Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With <i>BRAF</i> Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Label="PURPOSE" NlmCategory="OBJECTIVE">The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with <i>BRAF</i> mutations treated with cobimetinib plus vemurafenib are reported.

38096473

Efficacy and Tolerability of Osimertinib and Sotorasib Combination Treatment for Osimertinib Resistance Caused by <i>KRAS</i> G12C Mutation: A Report of Two Cases.

38096474

Prospective Characterization of Circulating Tumor Cell Kinetics in Patients With Oligometastatic Disease Receiving Definitive Intent Radiation Therapy.

There are currently no predictive molecular biomarkers to identify patients with oligometastatic disease (OMD) who will benefit from definitive-intent radiation therapy (RT). We prospectively characterized circulating tumor cell (CTC) kinetics in patients with OMD undergoing definitive-intent RT.

38096475

Patient Experience, Adverse Event Reporting, and Clinical Trial Design.

38096477

A high-quality pseudo-phased genome for Melaleuca quinquenervia shows allelic diversity of NLR-type resistance genes.

Melaleuca quinquenervia (broad-leaved paperbark) is a coastal wetland tree species that serves as a foundation species in eastern Australia, Indonesia, Papua New Guinea, and New Caledonia. While extensively cultivated for its ornamental value, it has also become invasive in regions like Florida, USA. Long-lived trees face diverse pest and pathogen pressures, and plant stress responses rely on immune receptors encoded by the nucleotide-binding leucine-rich repeat (NLR) gene family. However, the comprehensive annotation of NLR encoding genes has been challenging due to their clustering arrangement on chromosomes and highly repetitive domain structure; expansion of the NLR gene family is driven largely by tandem duplication. Additionally, the allelic diversity of the NLR gene family remains largely unexplored in outcrossing tree species, as many genomes are presented in their haploid, collapsed state.

38096476

Management of Scaphotrapeziotrapezoid Osteoarthritis: A Critical Analysis Review.

» The scaphotrapeziotrapezoid (STT) joint is a common location of degenerative osteoarthritis (OA) in the wrist.» STT OA may occur in isolation or with concomitant thumb carpometacarpal joint (CMCJ) OA or scapholunate advanced collapse (SLAC) and other wrist OA patterns.» Nonoperative management strategies include activity modification, bracing, anti-inflammatory medications, occupational therapy, and injections.» Surgical treatment may be determined by whether the STT OA occurs in isolation or with concomitant thumb CMCJ or SLAC OA and includes STT arthrodesis, distal scaphoid excision with or without interposition or implant arthroplasty, trapeziectomy with proximal trapezoid excision, four-corner fusion in combination with scaphoid/radial column excision, and proximal row carpectomy.

38096478

Tf₂O-Mediated Tandem Reaction of Enaminones for the Synthesis of Functionalized Conjugated-Enals/&#946;-Naphthalaldehydes.

A highly efficient and regioselective method for constructing functionalized conjugated enals <i>via</i> the Tf₂O-mediated tandem reaction of enaminones with thiophenols has been described. Chain products with excellent stereoselectivity could be obtained through substrate regulation. Additionally, a feasible method for synthesizing &#946;-naphthalaldehydes through PhSO₂Na/DABCO promoting hydrogen atom transfer process has also been reported here. Mechanism studies have shown that 2-formyl vinyl triflate <b>8</b> and sulfonylated enal <b>9</b> were the key intermediates in this process.

38096479

Stem-cell-expressed DEVIL-like small peptides maintain root growth under abiotic stress via abscisic acid signaling.

Stem cells are essential to plant growth and development. Through data mining, we identified five DEVIL-like (DVL) small peptide genes that are preferentially expressed in the quiescent center (QC) of Arabidopsis (Arabidopsis thaliana) root but whose functions are unknown. When overexpressed, these genes caused a dramatic decrease in root length and pleiotropic phenotypes in the shoot. No root growth defect was observed in the single gene mutants, but the quintuple mutant exhibited slightly longer roots than the wild type. Through transcriptome analysis with DVL20-overexpressing plants, we found that many genes involved in abscisic acid (ABA) signaling were regulated by these peptides. Consistent with this finding, we demonstrated that, relative to the wild type, DVL20-overexpressing plants were more tolerant whereas the quintuple mutant was more sensitive to ABA. Using RT-qPCR, we showed that ABA signaling-associated genes were affected in an opposite manner when the plants were grown in normal or ABA-containing medium. Strikingly, ectopic expression of ABA signaling genes such as PYRABACTIN RESISTANCE 1-LIKE (PYL) 4, 5 or 6 or suppression of HIGHLY ABA INDUCED 2 (HAI2) and MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 18 (MAPKKK18) not only largely rescued the root growth defects in DVL20-overexpressing plants in normal growth condition but also conferred tolerance to ABA. Based on these results, we propose that DVL1, 2, 5, 8 and 20 function redundantly in root stem-cell maintenance under abiotic stress, and this role is achieved via ABA signaling.

38096480

Overcoming Radical Stability Order via DABCO-Triggered Desulfurization: Visible-Light-Promoted 1,2,4-Trifunctionalization of Butenyl Benzothiazole Sulfone with Thiosulfonate.

A radical 1,2,4-trifunctional reaction of thiosulfonate to unactivated olefin is achieved by a migration strategy under mild conditions. In this reaction, the more unstable primary free radicals are in situ generated after the migration of heteroaryl groups in the presence of DABCO. This trifunctionalization of unactivated olefins involves two C-S bond formations and one C-C bond formation.

38096481

Channel Activities of the Full-Length Prion and Truncated Proteins.

Prion diseases are fatal neurodegenerative disorders characterized by the conversion of the cellular prion protein (PrP^C) into a misfolded prion form, which is believed to disrupt the cellular membranes. However, the exact mechanisms underlying prion toxicity, including the formation of membrane pores, are not fully understood. The prion protein consists of two domains: a globular domain (GD) and a flexible N-terminus (FT) domain. Although a proximal polybasic amino acid (FT(23-31) sequence of FT is a prerequisite for cellular membrane permeabilization, other functional domain regions may modulate its effects. Through single-channel electrical recordings and cryo-electron microscopy (cryo-EM), we discovered that the FT(23-50) fragment forms pore-shaped oligomers and plays a dominant role in membrane permeabilization within the full-length mouse prion protein (mPrP(23-230)). In contrast, the FT(51-110) domain or the C-terminal domain downregulate the channel activity of FT(23-50) and mPrP(23-230). The addition of prion mimetic antibody, POM1 significantly amplifies mPrP(23-230) membrane permeabilization, whereas POM1_Y104A, a mutant that binds to PrP but cannot elicit toxicity, has a negligible effect on membrane permeabilization. Additionally, the anti-N-terminal antibody POM2 or Cu²⁺ binds to the FT domain, subsequently enhancing the FT(23-110) channel activity. Importantly, our setup provides a novel approach without an external fused protein to examine the channel activity of truncated PrP in the lipid membranes. We therefore propose that the primary N-terminal residues are essential for membrane permeabilization, while other functional segments of PrP play a vital role in modulating the pathological effects of PrP-mediated neurotoxicity.

38096482

The Power of Poetry: Rethinking How We Use Language in Global Health Research.

38096483

Cancer stem cells as a therapeutic target: current clinical development and future prospective.

The key role of cancer stem cells (CSCs) in tumor development and therapy resistance makes them essential biomarkers and therapeutic targets. Numerous agents targeting CSCs, either as monotherapy or as part of combination therapy, are currently being tested in clinical trials to treat solid tumors and hematologic malignancies. Data from ongoing and additional clinical trials testing novel approaches to target tumor stemness-related biomarkers and pathways may pave the way for further clinical development of CSC-targeted treatments and CSC-guided selection of therapeutic regimens. In this concise review, we discuss recent progress in developing CSC-directed treatment approaches, focusing on clinical trials testing CSC-directed therapies. We also consider the further development of CSC-assay-guided patient stratification and treatment personalization.

38096484

Identification of genetic and environmental factors influencing aerial root traits that support biological nitrogen fixation in sorghum.

Plant breeding and genetics play a major role in the adaptation of plants to meet human needs. The current requirement to make agriculture more sustainable can be partly met by a greater reliance on biological nitrogen fixation (BNF) by symbiotic diazotrophic microorganisms that provide crop plants with ammonium. Select accessions of the cereal crop sorghum (Sorghum bicolor (L.) Moench) form mucilage-producing aerial roots that harbor nitrogen-fixing bacteria. Breeding programs aimed at developing sorghum varieties that support diazotrophs will benefit from a detailed understanding of the genetic and environmental factors contributing to aerial root formation. A genome-wide association study (GWAS) of the sorghum minicore, a collection of 242 landraces, and 30 accessions from the sorghum association panel (SAP) was conducted in Florida and Wisconsin and under two fertilizer treatments to identify loci associated with the number of nodes with aerial roots and aerial root diameter. Sequence variation in genes encoding transcription factors that control phytohormone signaling and root system architecture showed significant associations with these traits. In addition, the location had a significant effect on the phenotypes. Concurrently, we developed F2 populations from crosses between bioenergy sorghums and a landrace that produced extensive aerial roots to evaluate the mode of inheritance of the loci identified by the GWAS. Furthermore, the mucilage collected from aerial roots contained polysaccharides rich in galactose, arabinose, and fucose, whose composition displayed minimal variation among 10 genotypes and two fertilizer treatments. These combined results support the development of sorghums with the ability to acquire nitrogen via BNF.

38096485

Combined Quantum Mechanical and Quasi-Classical State-to-State Dynamical Study on the Isotopic Effect in H/D + LiH⁺/LiD⁺ &#8594; H₂/HD/D₂ + Li⁺ Reactions.

Coriolis-coupled quantum mechanical (QM-CC) and quasi-classical trajectory (QCT) calculations are carried out to investigate the dynamics of the H(D) + LiH⁺(<i>v</i> = 0, <i>j</i> = 0) &#8594; H₂(HD) (<i>v</i>', <i>j</i>') + Li⁺ reactions on the ground electronic state potential energy surface reported by Martinazzo et al. (Martinazzo et al., <i>J. Chem. Phys.</i> <b>2003</b>, <i>119</i>, 11241). The QM-CC and QCT results at the initial state-selected and state-to-state levels are used to investigate the validity and accuracy of the QCT method for these exoergic barrierless reactions. Furthermore, the QCT method is used to understand the isotopic effects on reaction observables like total and state-to-state integral cross section, differential cross section, product energy disposal, and rate constants of H(D) + LiH⁺(<i>v</i> = 0, <i>j</i> = 0) &#8594; H₂(HD) (<i>v</i>', <i>j</i>') + Li⁺ and H(D) + LiD⁺(<i>v</i> = 0, <i>j</i> = 0) &#8594; HD(D₂) (<i>v</i>', <i>j</i>') + Li⁺ reactions. Attempts are also made to understand the impact of the isotopic substitution on the reaction mechanism. It is observed that QM-CC and QCT results closely follow each other at the initial state-selected and state-to-state levels. Noticeable kinematic effects of reagents on the reactivity and mechanism of the reactions are also observed.

38096486

Controlling the 2D Magnetism of CrBr₃ by van der Waals Stacking Engineering.

The manipulation of two-dimensional (2D) magnetic order is of significant importance to facilitate future 2D magnets for low-power and high-speed spintronic devices. van der Waals stacking engineering makes promises for controllable magnetism via interlayer magnetic coupling. However, directly examining the stacking order changes accompanying magnetic order transitions at the atomic scale and preparing device-ready 2D magnets with controllable magnetic orders remain elusive. Here, we demonstrate the effective control of interlayer stacking in exfoliated CrBr₃ via thermally assisted strain engineering. The stable interlayer ferromagnetic (FM), antiferromagnetic (AFM), and FM-AFM coexistent ground states confirmed by the magnetic circular dichroism measurements are realized. Combined with the first-principles calculations, the atomically resolved imaging technique reveals the correlation between magnetic order and interlayer stacking order in CrBr₃ flakes unambiguously. A tunable exchange bias effect is obtained in the mixed phase of FM and AFM states. This work will introduce new magnetic properties by controlling the stacking order and sequence of 2D magnets, providing ample opportunities for their application in spintronic devices.

38096487

Computational Characterization of the Reactivity of Compound I in Unspecific Peroxygenases.

Unspecific peroxygenases (UPOs) are emerging as promising biocatalysts for selective oxyfunctionalization of unactivated C-H bonds. However, their potential in large-scale synthesis is currently constrained by suboptimal chemical selectivity. Improving the selectivity of UPOs requires a deep understanding of the molecular basis of their catalysis. Recent molecular simulations have sought to unravel UPO's selectivity and inform their design principles. However, most of these studies focused on substrate-binding poses. Few researchers have investigated how the reactivity of CpdI, the principal oxidizing intermediate in the catalytic cycle, influences selectivity in a realistic protein environment. Moreover, the influence of protein electrostatics on the reaction kinetics of CpdI has also been largely overlooked. To bridge this gap, we used multiscale simulations to interpret the regio- and enantioselective hydroxylation of the <i>n</i>-heptane substrate catalyzed by <i>Agrocybe aegerita</i> UPO (<i>Aae</i>UPO). We comprehensively characterized the energetics and kinetics of the hydrogen atom-transfer (HAT) step, initiated by CpdI, and the subsequent oxygen rebound step forming the product. Notably, our approach involved both free energy and potential energy evaluations in a quantum mechanics/molecular mechanics (QM/MM) setting, mitigating the dependence of results on the choice of initial conditions. These calculations illuminate the thermodynamics and kinetics of the HAT and oxygen rebound steps. Our findings highlight that both the conformational selection and the distinct chemical reactivity of different substrate hydrogen atoms together dictate the regio- and enantio-selectivity. Building on our previous study of CpdI's formation in <i>Aae</i>UPO, our results indicate that the HAT step is the rate-limiting step in the overall catalytic cycle. The subsequent oxygen rebound step is swift and retains the selectivity determined by the HAT step. We also pinpointed several polar and charged amino acid residues whose electrostatic potentials considerably influence the reaction barrier of the HAT step. Notably, the Glu196 residue is pivotal for both the CpdI's formation and participation in the HAT step. Our research offers in-depth insights into the catalytic cycle of <i>Aae</i>UPO, which will be instrumental in the rational design of UPOs with enhanced properties.

38096488

Tuning the Fluorometric Sensing of Phosphate on UiO-66-NH₂(Zr, Ce, Hf) Metal Nodes.

Metal-organic frameworks (MOFs) with intrinsic luminescent properties, modular structure, and tunable electronic properties, provide unique opportunities for designing target-specific molecular sensors by systematically choosing their constituent building blocks. We report a simple one-step MOF-based sensing platform for phosphate (P) detection that combines the luminescent properties of 2-aminoterephthalic acid (ATA) with the affinity of rationally selected nodes in UiO-66-NH₂ to bind with P. This MOF possesses an electron-donating amine group that controls the light-harvesting characteristics of the linkers. Substituting Zr₆ node with Ce₆ or Hf₆ results in a series of isostructural MOFs with distinct optical properties that are nonexistent in the unsubstituted MOF. We have utilized these MOFs to quantitatively measure P, using its ability to bind strongly to metal nodes inhibiting the LMCT process and altering the linker's photon emission. Using this system, detection limits of 4.5, 7.2 and 10.5 &#956;M were obtained for the UiO-66-NH₂(Ce), UiO-66-NH₂, and UiO-66-NH₂(Hf) respectively, adopting a straightforward single step procedure. These results demonstrate that the selection of metal nodes in a series of isostructural MOFs can be used to modulate their electronic properties and create sensing probes possessing the desired characteristics needed for the detection of environmental contaminants.

38096489

The dementia severity rating scale: A potential community screening tool for dementia in low- and middle-income countries.

The Dementia Severity Rating Scale (DSRS) is an informant report, dementia staging tool that is quick to administer and has previous been shown to differentiate between people with dementia and healthy controls. However, it is not clear how accurate the tool is screening against diagnostic criteria in middle-income settings.