Anomalous size dependence of the coercivity of nanopatterned CrGeTe3.

The coercivity of single-domain magnetic nanoparticles typically decreases with the nanoparticle size and reaches zero when thermal fluctuations overcome the magnetic anisotropy. Here, we used SQUID-on-tip microscopy to investigate the coercivity of square-shaped CrGeTe3 nanoislands with a wide range of sizes and width-to-thickness aspect ratios. The results reveal an anomalous size-dependent coercivity, with smaller islands exhibiting higher coercivity. The nonconventional scaling of the coercivity in CrGeTe3 nanoislands was found to be inversely proportional to the island width and thickness (1/wd). This scaling implies that the nanoisland magnetic anisotropy is proportional to the perimeter rather than the volume, suggesting a magnetic edge state. In addition, we observe that 1600 nm wide islands display multi-domain structures with zero net remnant field, corresponding to the magnetic properties of pristine CrGeTe3 flakes. Our findings highlight the significant influence of edge states on the magnetic properties of CrGeTe3 and deepen our understanding of low-dimensional magnetic systems.

Altering glycopeptide antibiotic biosynthesis through mutasynthesis allows incorporation of fluorinated phenylglycine residues.

Glycopeptide antibiotics (GPAs) are peptide natural products used as last resort treatments for antibiotic resistant bacterial infections. They are produced by the sequential activities of a linear nonribosomal peptide synthetase (NRPS), which assembles the heptapeptide core of GPAs, and cytochrome P450 (Oxy) enzymes, which perform a cascade of cyclisation reactions. The GPAs contain proteinogenic and nonproteinogenic amino acids, including phenylglycine residues such as 4-hydroxyphenylglycine (Hpg). The ability to incorporate non-proteinogenic amino acids in such peptides is a distinctive feature of the modular architecture of NRPSs, with each module selecting and incorporating a desired amino acid. Here, we have exploited this ability to produce and characterise GPA derivatives containing fluorinated phenylglycine (F-Phg) residues through a combination of mutasynthesis, biochemical, structural and bioactivity assays. Our data indicate that the incorporation of F-Phg residues is limited by poor acceptance by the NRPS machinery, and that the phenol moiety normally present on Hpg residues is essential to ensure both acceptance by the NRPS and the sequential cyclisation activity of Oxy enzymes. The principles learnt here may prove useful for the future production of GPA derivatives with more favourable properties through mixed feeding mutasynthesis approaches.

Isolation of a NHC-stabilized heavier nitrile and its conversion into an isonitrile analogue.

Nitriles (R-C≡N) have been investigated since the late eighteenth century and are ubiquitous encounters in organic and inorganic syntheses. In contrast, heavier nitriles, which contain the heavier analogues of carbon and nitrogen, are sparsely investigated species. Here we report the synthesis and isolation of a phosphino-silylene featuring an N-heterocyclic carbene-phosphinidene and a highly sterically demanding silyl group as substituents. Due to its unique structural motif, it can be regarded as a Lewis base-stabilized heavier nitrile. The Si-P bond displays multiple bond character and a bent R-Si-P geometry, the latter indicating fundamental differences between heavier and classical nitriles. In solution, a quantitative unusual rearrangement to a phosphasilenylidene occurs. This rearrangement is consistent with theoretical predictions of rearrangements from heavier nitriles to heavier isonitriles. Our preliminary reactivity studies revealed that both isomers exhibit highly nucleophilic silicon centres capable of oxidative addition and coordination to iron tetracarbonyl.

The chicken or the egg? Mycoplasma pneumoniae complicated by left ventricle thrombus and anterior myocardial infarction: a case report.

Background: Mycoplasma pneumoniae can be associated with extrapulmonary manifestations, including vasculitis, myocarditis, and thrombosis. In rare cases, it has also been implicated in intracardiac thrombus formation. Case Summary: A previously healthy 25-year-old male presented with worsening abdominal pain, an episode of acute chest pain, new lightheadedness, and gait instability in the setting of M. pneumoniae. Initial blood tests were notable for mild coagulopathy, thrombocytosis, transaminitis, and elevated high-sensitivity troponin. Further, workup revealed systematic emboli to the cerebellum, kidneys, spleen, anterior myocardial infarction, and a left ventricular multilobular mural mass. Due to the unknown composition of the mass with concern for further embolic events, the patient underwent successful surgical excision with the mass ultimately defined as a thrombus. Hypercoagulable workup was notably inconclusive and intraoperative myocardial biopsies revealed organizing infarction without inflammation or healed myocarditis. Post-operative course was complicated by left ventricular dysfunction and acute kidney injury, both with eventual improvement. Patient has remained on guideline-directed medical therapy and prophylactic anticoagulation. Discussion: We presume that the formation of the ventricular thrombus in this case was a result of transient thrombophilia in the setting of M. pneumonia resulting in coronary obstruction and subsequent myocardial injury. This case underscores the challenge of determining the pathophysiological sequence of events in patients with mycoplasma who develop systemic embolism and the management of a large residual thrombus, particularly in regard to surgical consideration.

Recent trends and disparities in 24-hour movement behaviors among US youth with mental, behavioral and neurodevelopmental conditions.

BACKGROUND: Meeting 24-h movement behaviors (24-HMB: physical activity [PA], screen time [ST], and sleep [SL]) recommendations may be associated with positive health outcomes among youth with specific mental, behavioral, and neurodevelopmental (MBD) conditions. However, temporal trends and disparities in meeting 24-HMB guidelines in these higher-risk groups have not been investigated, hampering the development of evidence-based clinical and public health interventions. METHODS: Serial, cross-sectional analyses of nationally National Survey of Children's Health (NSCH) data (including U.S. youth aged 6-17 years with MBD conditions) were conducted. The time-trends survey data was conducted between 2016 and 2021. The prevalence of 24-HMB adherence estimates were reported for the overall sample and for various sociodemographic subgroups. The subgroups analyzed included: age group (children[aged 6 to 13 years], adolescents[aged 14 to 17 years]), sex, socioeconomic status, and ethnicity. RESULTS: Data on 52,634 individuals (mean age, 12.0 years [SD,3.5]; 28,829 [58.0 %] boys) were analyzed. From 2016 to 2021 the estimated trend in meeting PA + ST + SL guidelines declined (-0.8 % [95%CI, -1.0 % to -0.5 %], P for trend <0.001), whereas meeting none of 24-HMB guidelines increased (2.2 % [1.8 % to 2.6 %], P for trend <0.001). White participants, children, and boys reported higher estimated prevalence of meeting full integrated (PA + ST + SL) guidelines. DISCUSSION: The temporal trends observed in this study highlight the importance of consistently monitoring movement behavior among MBD youth and identifying variations by sociodemographic groups in meeting 24-HMB guidelines for health promotion within these vulnerable groups.

Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation.

Background: The patterns of direct oral anticoagulant (DOAC) selection and switching to a different oral anticoagulant (OAC) in patients with atrial fibrillation (AF) are unknown. Objectives: To describe temporal patterns in first DOAC prescriptions, estimate the incidence, and identify predictors of switching to a different OAC within 1 year in OAC-naive AF patients. Methods: In this retrospective cohort study, using a near-nationwide prescription registry (IQVIA, the Netherlands), we determined the number of patients per month initiated on each DOAC and identified predictors of switching within 1 year with robust Poisson regression. Results: We included 94,874 patients. From November 2015 to November 2019, the monthly use of apixaban (n = 366 to n = 1066, +191%), rivaroxaban (n = 379 to n = 868, +129%), and edoxaban (n = 2 to n = 305, +15,150%) increased, whereas that of dabigatran decreased (n = 317 to n = 179, -44%). In the 66,090 patients with ≥1 year of available calendar time, 7% switched to a different OAC within 1 year. Strong predictors of switching to a different DOAC were using dabigatran (adjusted risk ratio [aRR], 3.33; 95% CI, 3.02-3.66) or edoxaban (aRR, 1.56; 95% CI, 1.34-1.82) rather than apixaban and using a standard DOAC dose (aRR, 2.54; 95% CI, 2.23-2.88). Strong predictors of switching to a vitamin K antagonist were using rivaroxaban (aRR, 1.36; 95% CI, 1.19-1.54 vs apixaban) and using a standard DOAC dose (aRR, 1.49; 95% CI, 1.26-1.77). Conclusion: In the Netherlands, factor Xa inhibitors are increasingly being selected for OAC-naive AF patients. Seven percent of patients switch to a different OAC within 1 year, and the initial DOAC type and dose are strong predictors of switching.

Phosphorylation of CRYAB Induces a Condensatopathy to Worsen Post-Myocardial Infarction Left Ventricular Remodeling.

Protein aggregates are emerging therapeutic targets in rare monogenic causes of cardiomyopathy and amyloid heart disease, but their role in more prevalent heart failure syndromes remains mechanistically unexamined. We observed mis-localization of desmin and sarcomeric proteins to aggregates in human myocardium with ischemic cardiomyopathy and in mouse hearts with post-myocardial infarction ventricular remodeling, mimicking findings of autosomal-dominant cardiomyopathy induced by R120G mutation in the cognate chaperone protein, CRYAB. In both syndromes, we demonstrate increased partitioning of CRYAB phosphorylated on serine-59 to NP40-insoluble aggregate-rich biochemical fraction. While CRYAB undergoes phase separation to form condensates, the phospho-mimetic mutation of serine-59 to aspartate (S59D) in CRYAB mimics R120G-CRYAB mutants with reduced condensate fluidity, formation of protein aggregates and increased cell death. Conversely, changing serine to alanine (phosphorylation-deficient mutation) at position 59 (S59A) restored condensate fluidity, and reduced both R120G-CRYAB aggregates and cell death. In mice, S59D CRYAB knock-in was sufficient to induce desmin mis-localization and myocardial protein aggregates, while S59A CRYAB knock-in rescued left ventricular systolic dysfunction post-myocardial infarction and preserved desmin localization with reduced myocardial protein aggregates. 25-Hydroxycholesterol attenuated CRYAB serine-59 phosphorylation and rescued post-myocardial infarction adverse remodeling. Thus, targeting CRYAB phosphorylation-induced condensatopathy is an attractive strategy to counter ischemic cardiomyopathy.

The neural signature of an erroneous thought.

The human brain detects errors in overt behavior fast and efficiently. However, little is known about how errors are monitored that emerge on a mental level. We investigate whether neural correlates of error monitoring can be found during inner speech and whether the involved neural processes differ between these non-motor responses and behavioral motor responses. Therefore, electroencephalographic data were collected while participants performed two versions of a decision task that only differed between these response modalities. Erroneous responses were identified based on participants' metacognitive judgments. Correlates of error monitoring in event-related potentials were analyzed by applying residue iteration decomposition on stimulus-locked activity. Non-motor responses elicited the same cascade of early error-related negativity and late error positivity as motor responses. An analysis of oscillatory brain activity showed a similar theta response for both error types. A multivariate pattern classifier trained on theta from the motor condition could decode theta from the non-motor condition, demonstrating the similarity of both neural responses. These results show that errors in inner speech are monitored and detected utilizing the same neural processes as behavioral errors, suggesting that goal-directed cognition and behavior are supported by a generic error-monitoring system.

Acute increase of protein O-GlcNAcylation in mice leads to transcriptome changes in the brain opposite to what is observed in Alzheimer's Disease.

Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) is explored as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the mechanistic path of using OGA inhibition to treat AD. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using OGA inhibitor Thiamet G (TG), on normal mouse brains. We hypothesized that the transcritome signature in respones to TG treatment provides a comprehensive view of the effect of OGA inhibition. We sacrificed the mice and dissected their brains after 3 hours of saline or 50 mg/kg TG treatment, and then performed mRNA sequencing using NovaSeq PE 150 (n=5 each group). We identified 1,234 significant differentially expressed genes with TG versus saline treatment. Functional enrichment analysis of the upregulated genes identified several upregulated pathways, including genes normally down in AD. Among the downregulated pathways were the cell adhesion pathway as well as genes normally up in AD and aging. When comparing acute to chronic TG treatment, protein autophosphorylation and kinase activity pathways were upregulated, whereas cell adhesion and astrocyte markers were downregulated in both datasets. Interestingly, mitochondrial genes and genes normally down in AD were up in acute treatment and down in chronic treatment. Data from this analysis will enable the evaluation of the mechanisms underlying the potential benefits of OGA inhibition in the treatment of AD. In particular, although OGA inhibitors are promising to treat AD, their downstream chronic effects related to bioenergetics may be a limiting factor.

Assessing the Quality of Solvent-Assisted Lipid Bilayers Formed at Different Phases and Aqueous Buffer Media: A QCM-D Study.

Supported lipid bilayers (SLBs) are low-complexity biomimetic membranes, serving as popular experimental platforms to study membrane organization and lipid transfer, membrane uptake of nanoparticles and biomolecules, and many other processes. Quartz crystal microbalance with dissipation monitoring has been utilized to probe the influence of several parameters on the quality of SLBs formed on Au- and SiO2-coated sensors. The influence of the aqueous medium (i.e., buffer type) and the adsorption temperature, above and below the lipid melting point, is neatly explored for SLBs of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine formed by a solvent exchange. Below the lipid melting temperature, quality variations are observed upon the formation on Au and SiO2 surfaces, with the SLBs being more homogeneous for the latter. We further investigate how the buffer affects the detection of lipid melting in SLBs, a transition that necessitates high-sensitivity and time-consuming surface-sensitive techniques to be detected.

Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023.

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.

The third symposium on treatment-induced neuroendocrine prostate cancer: insights and future directions.

Neuroendocrine prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer (PCa), emerging from advanced treatments and characterized by loss of androgen receptor (AR) signaling and neuroendocrine features, leading to rapid progression and treatment resistance. The third symposium on treatment-induced NEPC, held from 21 to 23 June 2024, at Harrison Hot Springs Resort, BC, Canada, united leading global researchers and clinicians. Sponsored by the Vancouver Prostate Centre (VPC), Canadian Institute of Health Research, Prostate Cancer Foundation Canada and Pharma Planter Inc, the event focused on the latest NEPC research and innovative treatment strategies. Co-chaired by Drs. Yuzhuo Wang and Martin Gleave, the symposium featured sessions on NEPC's historical context, molecular pathways, epigenetic regulation and the role of the tumor microenvironment and metabolism in its progression. Keynotes from experts like Dr. Himisha Beltran and Dr. Martin Gleave highlighted the complexity of NEPC. The Emerging Talent session showcased new research, pointing to the future of NEPC treatment. The symposium concluded with a consensus on the need for early detection, targeted therapies and personalized medicine to effectively combat NEPC, emphasizing the importance of global collaboration in advancing NEPC understanding and treatment.

Cine-MRI and T1TSE Sequence for Mediastinal Mass.

Background/Objectives: Contrast-enhanced computed tomography (CT) is the standard radiologic examination for evaluating the extent of mediastinal tumors. If tumor infiltration into the large central thoracic vessels, the pericardium, or the myocardium is suspected, cine magnetic resonance imaging (cine-MRI) can provide additional valuable information. Methods: We conducted a retrospective study of patients with mediastinal tumors who were staged with CT, cine-MRI, and a T1-weighted turbo spin echo (T1TSE) prior to surgical resection. Imaging was re-evaluated regarding tumor infiltration into the pericardium, myocardium, superior vena cava, aorta, pulmonary arteries, and atria and compared with intraoperative findings and postoperative histopathological reports (gold standard). Unclear CT findings were further investigated. Results: Forty-seven patients (29 female and 18 male patients; median age: 58 years) met the inclusion criteria. Cine-MRI was able to predict infiltration of the aorta in 86%, pulmonary arteries in 85%, and atria in 80% of unclear CT cases. Aortic tumor infiltration in unclear CT cases was significantly more often correctly diagnosed with cine-MRI than with T1TSE sequence. Conclusions: Additional cine-MRI is of crucial benefit in unclear CT cases. We recommend performing cine-MRI if infiltration into the large central vessels and atria is suspected. T1TSE sequence is of very limited additional value.

[Metabolic, clinical and body composition changes in Mexican adults undergoing bariatric surgery]. / Cambios metabólicos, clínicos y de composición corporal en adultos mexicanos sometidos a cirugía bariátrica.

BACKGROUND: morbid obesity is a major public health problem that is increasing. Currently, there are a limited number of studies carried out in the Mexican population that describe the effects of bariatric surgery. OBJECTIVE: to establish in people undergoing a bariatric procedure the metabolic and body composition difference before and after bariatric surgery. MATERIAL AND METHODS: an observational, analytical, and longitudinal study was carried out in 50 patients with morbid obesity who underwent laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Roux-en-Y gastric bypass (LRYGB). Body composition and metabolic markers in blood were measured. Differences in the metabolic profile before and after surgery were analyzed in the entire study group and a subanalysis was performed by bariatric surgical technique, determining the percentage of remission of comorbidities. RESULTS: after the intervention, there is a significant decrease in all metabolic and body composition markers, except HDL cholesterol, which showed a tendency to increase without being significant. Women with LRYGB have a greater decrease in fat-free mass. LRYGB decreased the prevalence of fatty liver, gastroesophageal reflux, insulin resistance, and hypercholesterolemia more, while LSG decreased the prevalence of hypertension, osteoarthritis, hypothyroidism, and hypertriglyceridemia more. CONCLUSION: bariatric surgery induces metabolic changes that could contribute to improving comorbidities associated with obesity. In general, metabolic improvement is greater in LRYGB compared to LSG.

Incidental Pulmonary Nodules: Differential Diagnosis and Clinical Management.

BACKGROUND: According to data from the USA, the incidence of incidentally discovered pulmonary nodules is 5.8 per 100 000 person-years for women and 5.2 per 100 000 person-years for men. Their management as recommended in the pertinent guidelines can substantially improve clinical outcomes. More than 95% of all pulmonary nodules revealed by computed tomography (CT) are benign, but many cases are not managed in conformity with the guidelines. In this article, we summarize the appropriate clinical approach and provide an overview of the pertinent diagnostic studies and when they should be performed. METHODS: This review is based on relevant publications retrieved by a selective search in PubMed. The authors examined English-language recommendations issued since 2010 for the management of pulmonary nodules, supplemented by comments from the German lung cancer guideline. RESULTS: In general, the risk that an incidentally discovered pulmonary nodule is malignant is low but rises markedly with increasing size and the presence of risk factors. When such a nodule is detected, the further recommendation, depending on size, is either for follow-up examinations with chest CT or else for an extended evaluation with positron emission tomography-CT and biopsy for histology. The diagnostic evaluation should include consideration of any earlier imaging studies that may be available as an indication of possible growth over time. Single nodules measuring less than 6 mm, in patients with few or no risk factors, do not require any follow-up. Lung cancer is diagnosed in just under 10% of patients with a nodule measuring more than 8 mm. CONCLUSION: The recommendations of the guidelines for the management of incidentally discovered pulmonary nodules are intended to prevent both over- and undertreatment. If a tumor is suspected, further care should be provided by an interdisciplinary team.

Pollution gradients shape microbial communities associated with ae. albopictus larval habitats in urban community gardens.

The Asian tiger mosquito Aedes albopictus is well adapted to urban environments and takes advantage of the artificial containers that proliferate in anthropized landscapes. Little is known about the physicochemical, pollutant and microbiota compositions of Ae. albopictus-colonized aquatic habitats and whether these properties differ with noncolonized habitats. We specifically addressed this question in French community gardens by investigating whether pollution gradients (characterized either by water physicochemical properties combined with pollution variables or by the presence of organic molecules in water) influence water microbial composition and then the presence/absence of Ae. albopictus mosquitoes. Interestingly, we showed that the physicochemical and microbial compositions of noncolonized and colonized waters did not significantly differ, with the exception of N2O and CH4 concentrations, which were higher in noncolonized water samples. Moreover, the microbial composition of larval habitats covaried differentially along the pollution gradients according to colonization status. This study opens new avenues on the impact of pollution on mosquito habitats in urban areas and raises questions on the influence of biotic and abiotic interactions on adult life history traits and their ability to transmit pathogens to humans.

Impact of O -GlcNAcylation elevation on mitophagy and glia in the dentate gyrus.

O -GlcNAcylation is a dynamic and reversible protein post-translational modification of serine or threonine residues which modulates the activity of transcriptional and signaling pathways and controls cellular responses to metabolic and inflammatory stressors. We and others have shown that O -GlcNAcylation has the potential to regulate autophagy and mitophagy to play a critical role in mitochondrial quality control, but this has not been assessed in vivo in the brain. This is important since mitochondrial dysfunction contributes to the development of neurodegenerative disease. We used mito-QC reporter mice to assess mitophagy in diverse cells in the dentate gyrus in response to pharmacological inhibition of OGA with thiamet G which leads to elevation of protein O -GlcNAcylation. We demonstrate that mitophagy occurs predominantly in the GFAP positive astrocytes and is significantly decreased in response to elevated O -GlcNAcylation. Furthermore, with increased O -GlcNAcylation, the levels of astrocyte makers GFAP and S100B, and microglial cell marker IBA1 were decreased in the dentate gyrus, while the levels of microglial cell marker TMEM119 were increased, indicating significant changes in glia homeostasis. These results provide strong evidence of the regulation of mitophagy and glia signatures by the O -GlcNAc pathway.

Knowledge and Perceptions about Diagnosis, Clinical Management, and Prevention of Dengue Fever among Physicians during the 2023 Outbreak: A Cross-Sectional Study in Peru.

The objective of this study was to evaluate the knowledge level and perception of dengue fever management among Peruvian physicians and to determine the factors associated with higher knowledge. We conducted an analytical cross-sectional study based on an online survey. To evaluate the factors associated with a high level of knowledge (≥70% of correct answers), we used crude (cPR) and adjusted (aPR) prevalence ratios by the Poisson regression model. Of 359 respondents (median age: 33 years; male: 56.5%), 78.8% achieved a high level of knowledge. Multivariable analysis showed an independent association with having read the Peruvian clinical practice guidelines for dengue management (aPR: 1.29; 95% CI: 1.12-1.49), having experience in treating patients (aPR: 1.32; 95% CI: 1.03-1.68), and having treated cases frequently (aPR: 1.22; 95% CI: 1.02-1.46). Residing in the eastern macroregion (aPR: 0.83; 95% CI: 0.71-0.97) was associated with a low level of knowledge. In conclusion, Peruvian physicians had a high level of knowledge about dengue fever. This was associated with having clinical experience in dengue management. However, given the low level of knowledge in the eastern macroregion, educational campaigns are necessary in this area.

Community assessment of methods to deconvolve cellular composition from bulk gene expression.

We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.