Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Rich essential properties of silicon-substituted graphene nanoribbons: a comprehensive computational study.

The diverse structural, electronic, and magnetic properties of silicon (Si)-substituted armchair and zigzag graphene nanoribbons (AGNRs and ZGNRs) were investigated using spin-polarized density functional theory (DFT) calculations. Pristine AGNRs belong to a nonmagnetic semiconductor with a direct bandgap of 1.63/1.92 eV determined by PBE/HSE06 functionals. Under various Si substitutions, nonmagnetic bandgaps were tuned at 1.49/1.87, 1.06/1.84, 0.81/1.45, 1.04/1.71, 0.89/1.05, and 2.38/3.0 eV (PBE/HSE06) in the single Si edge-, single Si non-edge-, double Si ortho-, double Si meta-, double Si para-, and 100% Si-substituted AGNR configurations, respectively. Meanwhile, pristine ZGNRs displayed antiferromagnetic semiconducting behavior with a spin degenerate bandgap of 0.52/0.81 eV (PBE/HSE06) and becomes a ferromagnetic semimetal in the single Si configurations or an unusual ferromagnetic semiconductor in the 100% Si configuration. Under the developed first-principles theoretical framework, the formation of quasi π (C-2pz and Si-3pz) and quasi σ (C-2s, -2pxy and Si-3s and -3pxy) bands was identified in the Si-substituted configurations. These quasi π and quasi σ bands showed weak separation, resulting in weak quasi sp2 hybridization in Si-C bonds, in which the identified hybridization mechanism was a strong evidence for the formation of stable planar 1D structures in the Si-substituted configurations. Our complete revelation of the essential properties of Si-substituted GNRs can provide a complete understanding of their chemically doped 1D materials for various practical applications.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Contrast Staining in Noninfarcted Tissue after Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Contrast staining is a common finding after endovascular treatment of acute ischemic stroke. It typically occurs in infarcted tissue and is considered an indicator of irreversible brain damage. Contrast staining in noninfarcted tissue has not been systematically investigated. We sought to assess the incidence, risk factors, and clinical significance of contrast staining in noninfarcted tissue after endovascular treatment. MATERIALS AND METHODS: We conducted a retrospective review of consecutive patients who underwent endovascular treatment for anterior circulation large-vessel occlusion acute ischemic stroke. Contrast staining, defined as new hyperdensity on CT after endovascular treatment, was categorized as either contrast staining in infarcted tissue if the stained region demonstrated restricted diffusion on follow-up MR imaging or contrast staining in noninfarcted tissue if the stained region demonstrated no restricted diffusion. Baseline differences between patients with and without contrast staining in noninfarcted tissue were compared. Logistic regression was used to identify independent associations for contrast staining in noninfarcted tissue after endovascular treatment. RESULTS: Among 194 patients who underwent endovascular treatment for large-vessel occlusion acute ischemic stroke and met the inclusion criteria, contrast staining in infarcted tissue was noted in 52/194 (26.8%) patients; contrast staining in noninfarcted tissue, in 26 (13.4%) patients. Both contrast staining in infarcted tissue and contrast staining in noninfarcted tissue were noted in 5.6% (11/194). Patients with contrast staining in noninfarcted tissue were found to have a higher likelihood of having an ASPECTS of 8-10, to be associated with contrast staining in infarcted tissue, and to achieve successful reperfusion compared with those without contrast staining in noninfarcted tissue. In contrast staining in noninfarcted tissue regions, the average attenuation was 40 HU, significantly lower than the contrast staining in infarcted tissue regions (53 HU). None of the patients with contrast staining in noninfarcted tissue had clinical worsening during their hospital stay. The median discharge mRS was significantly lower in patients with contrast staining in noninfarcted tissue than in those without (3 versus 4; P = .018). No independent predictors of contrast staining in noninfarcted tissue were found. CONCLUSIONS: Contrast staining can be seen outside the infarcted tissue after endovascular treatment of acute ischemic stroke, likely attributable to the reversible disruption of the BBB in ischemic but not infarcted tissue. While generally benign, understanding its characteristics is important because it may mimic pathologic conditions such as infarcted tissue and cerebral edema.

Validation of the Disaster Adaptation and Resilience Scale for Vulnerable Communities in Vietnam's Coastal Regions.

Objective: This study validated the Vietnamese version of the Disaster Adaptation and Resilience Scale (DARS) for use in vulnerable communities in Vietnam. Methods: This was a cross-sectional study involving 595 adults from 2 identified communities. The original DARS assessment tool was translated, and the validity and reliability of the Vietnamese version of DARS (V-DARS) were assessed. The internal consistency of the overall scale and its subscales was evaluated using Cronbach's alpha and McDonald's omega reliability coefficients. Confirmatory factor analysis (CFA) was employed to evaluate its construct validity, building upon the factor structure identified in exploratory factor analysis (EFA). Construct validity was assessed based on convergent and discriminant validity. Results: Following the established criteria for EFA, 8 items were removed, resulting in a refined V-DARS structure comprising 35 items distributed across 5 distinct factors. Both alpha and omega reliability coefficients indicated strong internal consistency for the overall scale (α = .963, ω = .963) and for each of the 5 sub-scales (all > 0.80). The CFA model also retained the 5-factor structure with 35 items. The model fit indices showed acceptable values (RMSEA: 0.072; CFI: 0.912; TLI: 0.904; chi-square test: <0.01). Additionally, the convergent and discriminant validity of the V-DARS were deemed appropriate and satisfactory for explaining the measurement structure. Conclusions: Our findings suggest that the V-DARS is a valid and reliable scale for use within vulnerable communities in Vietnam to assess adaptive responses to natural disasters. It may also be considered for use in other populations.

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

The influence of attributes on community preferences regarding antibiotic treatment: evidence from a discrete choice model.

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Cannabidiol use in France in 2022: Results from a nationwide representative sample of adults.

INTRODUCTION: Cannabidiol (CBD) is a non-intoxicating cannabis compound found in diverse commercial products worldwide. However, its use may not be fully harmless. Accordingly, it is important to document the prevalence of CBD use and user characteristics in the general population. METHODS: We conducted a nationwide survey from a random sample of adults living in France using computer-assisted telephone interviews between 2 March and 9 July 2022. We estimated the prevalence of CBD awareness and CBD use, and explored the different routes of administration. We also performed logistic regression models to identify factors associated with past-year CBD use. RESULTS: Based on data from 3229 participants, we estimated that 71.0% (95% confidence interval) (69.0-73.0) of the French adult population had heard of CBD, and 10.1% (8.7-11.4) had used it in the previous year. Past-year CBD use was associated with younger age, a higher educational level, not living in a middle-sized urban unit, tobacco consumption and e-cigarette use. The most common route of administration was smoking (56.1%). DISCUSSION AND CONCLUSION: Past-year CBD use prevalence in France appeared to be as high as that for cannabis. Proper prevention, regulation and control of CBD products is necessary to ensure that people have access to safe and high-quality products. Reliable information on CBD should be sought and disseminated, especially regarding the harms associated with smoking the compound.

Impact of obesity-related indicators on first-pass effect in patients with ischemic stroke receiving mechanical thrombectomy.

PURPOSE: The first-pass effect (FPE), defined as complete revascularization after a single thrombectomy pass in large vessel occlusion, is a predictor of good prognosis in patients with acute ischemic stroke (AIS) receiving mechanical thrombectomy (MT). We aimed to evaluate obesity-related indicators if possible be predictors of FPE. METHODS: We consecutively enrolled patients with AIS who were treated with MT between January 2019 and December 2021 at our institution. Baseline characteristics, procedure-related data, and laboratory test results were retrospectively analyzed. A multivariable logistic regression analysis was performed to evaluate the independent predictors of FPE. RESULTS: A total of 151 patients were included in this study, of whom 47 (31.1%) had FPE. After adjusting for confounding factors, the independent predictors of achieving FPE were low levels of body mass index (BMI) (OR 0.85, 95% CI 0.748 to 0.971), non-intracranial atherosclerotic stenosis (OR 4.038, 95% CI 1.46 to 11.14), and non-internal carotid artery occlusion (OR 13.14, 95% CI 2.394 to 72.11). Patients with lower total cholesterol (TC) (< 3.11 mmol/L) were more likely to develop FPE than those with higher TC (≥ 4.63 mmol/L) (OR 4.280; 95% CI 1.24 to 14.74) CONCLUSION: Lower BMI, non-intracranial atherosclerotic stenosis, non-internal carotid artery occlusion, and lower TC levels were independently associated with increased rates of FPE in patients with AIS who received MT therapy. FPE was correlated with better clinical outcomes after MT.

Mental health impact on healthcare workers from COVID-19 in Vietnam: Suggestions for a preventive program.

The COVID-19 pandemic has had a negative impact on the mental health of healthcare workers participating in the prevention and control of the pandemic, thereby reducing their quality of life and affecting the quality of patient outcomes. This study aims to explore and deeply understand the mental health problems among healthcare workers participating in the prevention and control of COVID-19 in Ho Chi Minh City, Vietnam. A mixed methods study was undertaken with a descriptive cross-sectional survey of 2870 healthcare workers who have been participating in the prevention and control of COVID-19 in Ho Chi Minh City in 2021, followed by a qualitative descriptive phenomenological study comprised of in-depth interviews with a purposively sampled subset of 40 healthcare workers. Results showed that of the 2870 survey participants, the majority (60.6%) were female, and the average age was 35.1 (SD = 8.6). The prevalence of stress, anxiety and depression was 17.2%, 20.8%, and 17.6%, respectively. The findings from in-depth interviews revealed that the participants were under extreme mental health issues such as worries, stress, and negative emotions. The worrying was related to risk of infection, being shunned, stigmatised, or assaulted by the community. Stress was due to excessive pressure from work. Negative emotions were identified as sadness, self-pity, feelings of loneliness, entrusting fate, feelings of guilt, anxiety, confusion, obsession, disorientation, physical and mental exhaustion. Promoting mental health among healthcare workers who participated in the crisis is necessary and urgent.

Base- and sulfur-promoted oxidative lactonization of chalcone-acetate Michael adducts: access to pyran-2-ones.

A cost-effective, practical, straightforward and scalable synthesis of α-pyrones via base- and sulfur-promoted annulation of phenylacetates and chalcones is reported. Generated in situ from the starting components by using dbu as a base catalyst, the Michael adducts underwent a smooth oxidative cyclization into 3,4,6-triaryl-2-pyranones upon heating with DABCO and sulfur in DMSO. Extension to malonate in place of phenylacetates led to 4,6-diaryl-2-pyranone-2-carboxylates.

Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Tobacco endgame measures and their adaptation in selected European countries: A narrative review synthesis.

Due to the continued detrimental effects of tobacco use, a growing number of countries are embracing the idea of tobacco endgame, meaning ending the tobacco epidemic instead of controlling it. This narrative review aims to synthesize and update the evidence from earlier scientific reviews on effective tobacco endgame measures, as well as to assess their integration to current national strategies among European countries with official tobacco endgame goals. The synthesis of the prior scientific literature found most evidence on product-focused and some evidence for supply-focused policies. Little evidence was detected for user- and institutional-focused measures. An update for the tobacco-free generation measure showed uncertainty in reducing smoking prevalence, especially for adolescents' reactions to age-restrictive laws. All the countries that established a tobacco endgame strategy have included product standards in their measures, predominantly based on European Union regulations on conventional tobacco products, yet standards above this level and considering other products were also common. Cessation measures were given strong emphasis in strategies, yet none of the countries linked these to specific endgame measures. Despite commonly mentioning vulnerable groups, such as youth and pregnant women, adoption of measures to reduce tobacco use among these groups was scarce. Lastly, the decline in tobacco use seems to be modest, implying challenges in meeting the endgame goals. To meet these goals, European countries should reinforce the implementation of known effective tobacco control measures such as tax increases. Furthermore, new innovative strategies and measures to meet the objective of an endgame should be explored.

Radiotolerance of N-cycle bacteria and their transcriptomic response to low-dose space-analogue ionizing irradiation.

The advancement of regenerative life support systems (RLSS) is crucial to allow long-distance space travel. Within the Micro-Ecological Life Support System Alternative (MELiSSA), efficient nitrogen recovery from urine and other waste streams is vital to produce liquid fertilizer to feed food and oxygen production in subsequent photoautotrophic processes. This study explores the effects of ionizing radiation on nitrogen cycle bacteria that transform urea to nitrate. In particular, we assess the radiotolerance of Comamonas testosteroni, Nitrosomonas europaea, and Nitrobacter winogradskyi after exposure to acute γ-irradiation. Moreover, a comprehensive whole transcriptome analysis elucidates the effects of spaceflight-analogue low-dose ionizing radiation on the individual axenic strains and on their synthetic community o. This research sheds light on how the spaceflight environment could affect ureolysis and nitrification processes from a transcriptomic perspective.

Oxygen vacancy-rich high-pressure rocksalt phase of zinc oxide for enhanced photocatalytic hydrogen evolution.

The generation of hydrogen as a clean energy carrier by photocatalysis, as a zero-emission technology, is of significant scientific and industrial interest. However, the main drawback of photocatalytic hydrogen generation from water splitting is its low efficiency compared to traditional chemical or electrochemical methods. Zinc oxide (ZnO) with the wurtzite phase is one of the most investigated photocatalysts for hydrogen production, but its activity still needs to be improved. In this study, an oxygen-deficient high-pressure ZnO rocksalt phase is stabilized using a high-pressure torsion (HPT) method, and the product is used for photocatalysis under ambient pressure. The simultaneous introduction of oxygen vacancies and the rocksalt phase effectively improved photocatalytic hydrogen production to levels comparable to benchmark P25 TiO2, due to improving light absorbance and providing active sites for photocatalysis without any negative effect on electron-hole recombination. These results confirm the high potential of high-pressure phases for photocatalytic hydrogen generation.

Semiclassical Truncated-Wigner-Approximation Theory of Molecular Vibration-Polariton Dynamics in Optical Cavities.

It has been experimentally demonstrated that molecular-vibration polaritons formed by strong coupling of a molecular vibration to an infrared cavity mode can significantly modify the physical properties and chemical reactivities of various molecular systems. However, a complete theoretical understanding of the underlying mechanisms of the modifications remains elusive due to the complexity of the hybrid system, especially the collective nature of polaritonic states in systems containing many molecules. We develop here the semiclassical theory of molecular vibration-polariton dynamics based on the truncated Wigner approximation (TWA) that is tractable in large molecular systems and simultaneously captures the quantum character of photons in the optical cavity. The theory is then applied to investigate the nuclear quantum dynamics of a system of identical diatomic molecules having the ground-state Morse potential and being strongly coupled to an infrared cavity mode in the ultrastrong coupling regime. The validity of TWA is examined by comparing it with the full quantum dynamics of a single-molecule system for two different initial states in the dipole and Coulomb gauges. For the initial tensor-product ground state in the dipole gauge, which corresponds to a light-matter entangled state in the Coulomb gauge, the collective and resonance effects of molecular vibration-polariton formation on the nuclear dynamics are observed in a system of many molecules.

Cell-cycle-specific autoencoding improves cluster analysis of cycling cardiomyocytes.

BACKGROUND: Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained non-cycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term "cell cycle." METHODS: Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle-specific analytical pipeline. Cycling cells were identified via the co-expression of five proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5). RESULTS: The cell-cycle-specific autoencoder (CSA) algorithm identified seven cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, two of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the two weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, and whereas pCM3 was enriched for the expression of a cell-cycle activator that regulates the G1/S phase transition (Cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (Cyclin B2). We also identified four transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the two weeks after MI induction. CONCLUSIONS: The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across three clusters that appeared to track the onset and progression of cell-cycle activity in cardiomyocytes from fetal pigs.

Role of Calprotectin, IL-6, and CRP in Distinguishing Between Inflammatory Bowel Disease and Diarrhea Predominant Irritable Bowel Syndrome.

Background: The early establishment of prophylaxis and immediate administration of anticoagulant therapy upon the diagnosis of venous thromboembolism should be the treatment objectives in these patients. Objective: The study aimed to determine the optimal cut-off point of Calprotectin, IL-6 (interleukin-6), CRP (C reactive protein) to differentiate UC, IBS-D. Methods: A cross-sectional descriptive study of 335 individuals ≥15 years old was performed, including 31 healthy controls, 215 with IBS-D, 71 diagnosed with UC, and 18 diagnosed with CD. Receiver Operating Characteristics (ROC), sensitivity, specificity, and area under curve (AUC) were computed. Results: The results showed that the median value of calprotectin (IQR) in healthy participants was 20.0 (6.0 - 34.0) µg/g; 17,7 (8,7-38,9) µg/g in IBS-D group; 1710.0 (588 - 4260,0) µg/g in UC group; and 560.5 (177.8 - 1210.0) µg/g in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of CRP (range IQR) was 1,3 (0,9 - 2,3) mg/L in IBS-D group; 7.0 (2.4 -16.6) mg/L in UC group; and 10.1 (2.2 - 42.5) mg/L in CD group. CRP concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of IL-6 (range IQR) was 2.3 (1.6 - 5.7) pg/mL in IBS-D group; 16.8 (9.4 - 47.0) pg/mL in UC group; and 9.4 (7.9 - 11.0) pg/mL in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The optimal cut-off point of calprotectin that differentiated IBS-D from IBD was 110.5 µg/g, with sensitivity and specificity of 93.3% and 91.4%, respectively; of IL-6 was 7.2 pg/mL with sensitivity and specificity of 92.0% and 78.0%, respectively; of CRP of 2.4 mg/L had specific sensitivities of 83.3% and 86.0%, respectively. Conclusion: The Calprotectin immunoassay has the best value in discriminating between IBD and IBS-D.

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19.

INTRODUCTION: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. PATIENTS AND METHODS: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. RESULTS: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). CONCLUSION: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.