How Shell Add-On Products Influence Varsity Football Helmet Performance?

PURPOSE: The study purpose was to investigate the laboratory-based performance of three commercially available shell add-on products under varsity-level impact conditions. METHODS: Pendulum impact tests were conducted at multiple locations (front, front boss, rear, side) and speeds (3.1, 4.9, 6.4 m/s) using two helmet models. Tests were performed with a single add-on configuration for baseline comparisons and a double add-on configuration to simulate collisions with both players wearing shell add-ons. A linear mixed-effect model was used to evaluate peak linear acceleration (PLA), peak rotational acceleration (PRA), and concussion risk, which was calculated from a bivariate injury risk function, based on shell add-on and test configuration. RESULTS: All shell add-ons decreased peak head kinematics and injury risk compared to controls, with the Guardian NXT producing the largest reductions (PLA: 7.9%, PRA: 14.1%, Risk: 34.1%) compared to the SAFR Helmet Cover (PLA: 4.5%, PRA: 9.3%, Risk: 24.7%) and Guardian XT (PLA: 3.2%, PRA: 5.0%, Risk: 15.5%). The same trend was observed in the double add-on test configuration. However, the Guardian NXT (PLA: 17.1%; PRA: 11.5%; Risk: 62.8%) and SAFR Helmet Cover (PLA: 12.2%; PRA: 9.1%; Risk: 52.2%) produced larger reductions in peak head kinematics and injury risk than the Guardian XT (PLA: 5.7%, PRA: 2.2%, Risk: 21.8%). CONCLUSION: In laboratory-based assessments that simulated varsity-level impact conditions, the Guardian NXT was associated with larger reductions in PLA, PRA, and injury risk compared to the SAFR Helmet Cover and Guardian XT. Although shell add-ons can enhance head protection, helmet model selection should be prioritized.

Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles.

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.

Epilipidomics reveals lipid fatty acid and headgroup modification in gas plasma-oxidized biomembranes.

Lipids, possessing unsaturated fatty acid chains and polar regions with nucleophilic heteroatoms, represent suitable oxidation targets for autologous and heterologous reactive species. Lipid peroxidation products (LPPs) are highly heterogeneous, including hydroperoxides, alkenals, chlorination, or glycation. Accordingly, delineation of lipid targets, species type, resulting products, and oxidation level remains challenging. To this end, liposomal biomimetic models incorporating a phosphatidylcholine, -ethanolamine, and a sphingomyelin were used to deconvolute effects on a single lipid scale to predict potential modification product outcomes. To introduce oxidative modifications, gas plasma technology, a powerful pro-oxidant tool to promote LPP formation by forming highly abundant reactive species in the gas and liquid phases, was employed to liposomes. The plasma parameters (gas type/combination) were modified to modulate the resulting species-profile and LPP formation by enriching specific reactive species types over others. HR-LC-MS (Münzel and et al., 2017) [2] was employed for LPP identification. Moreover, the heavy oxygen isotope 18O was used to trace O2-incorporation into LPPs, providing first information on the plasma-mediated lipid peroxidation mechanism. We found that combination of lipid class and gas composition predetermined the type of attack: admixture of O2 to the plasma and the presence of nitrogen atoms with free electrons in the molecule lead to chlorination of the amide bond and headgroup. Here, atomic oxygen driven formation of hypochlorite is the major reactive species. In contrast, POPC yields mainly to LPPs with oxidation of the oleic acid tail, especially truncations, epoxidation, and hydroperoxide formation. Here, singlet oxygen is assumingly the major driver. 18O labelling revealed that gas phase derived reactive species are dominantly incorporated into the LPPs, supporting previous findings on gas-liquid interface chemistry. In summary, we here provided the first insights into gas plasma-mediated lipid peroxidation, which, employed in more complex cell and tissue models, may support identifying mechanisms of actions in plasma medicine.

Classification of cyclic alternating patterns of sleep using EEG signals.

Cyclic alternating patterns (CAP) occur in electroencephalogram (EEG) signals during non-rapid eye movement sleep. The analysis of CAP can offer insights into various sleep disorders. The first step is the identification of phases A and B for the CAP cycles. In this work, we develop an easy-to-implement accurate system to differentiate between CAP A and CAP B. Small segments of the EEG signal are processed using Gaussian filters to obtain sub-band components. Features are extracted using some statistical characteristics of these signal components. Minimum redundancy maximum relevance test is employed to identify the more significant features. Three different machine learning classifiers are considered and their performance is compared. The results are analyzed for both the balanced and unbalanced datasets. The k-nearest neighbour (kNN) classifier achieves 79.14 % accuracy and F-1 score of 79.24 % for the balanced dataset. The proposed method outperforms the existing methods for CAP classification. It is easy-to-implement and can be considered as a candidate for real-time deployment.

Glycosylphosphatidylinositol-anchored lipid transfer proteins influence root cap cuticle formation at primary root tips, promoting NaCl tolerance in Arabidopsis seedlings.

Root cap cuticles (RCCs), comprising mainly very-long-chain fatty acids (VLCFAs), promote salt tolerance by preventing ion influx. Glycosylphosphatidylinositol-anchored lipid transfer protein (LTPG)1 and LTPG2 participate in VLCFA deposition in the extracellular region, aiding RCC formation in the lateral roots. In this study, we investigated whether LTPG1 and LTPG2 have similar functions in the primary roots of young Arabidopsis thaliana. Phenotypic analyses, fluorescence microscopy, and RT-qPCR confirmed that NaCl exposure induced LTPG1 and LTPG2 expression and promoted RCC formation in young primary roots. The loss of RCC in the ltpg1 and ltpg2 mutants resulted in increased NaCl sensitivity of root elongation. NaCl also upregulated the expression of several NaCl-responsive genes in ltpg1 and ltpg2. We conclude that RCC formation via LTPG function is pivotal in enhancing salt tolerance in young primary roots.

An Unlikely Case of Blastomycosis in an Elderly Female: A Diagnostic Challenge in a Non-endemic Region.

Blastomyces dermatitidis is a fungus typically found in the soil of endemic regions such as the Midwest, concentrating in areas like Ohio, Mississippi, and the Great Lakes area. The systemic infection caused by inhaling Blastomyces dermatitidis is known as blastomycosis. The frequency of blastomycosis in non-endemic regions is increasing for a variety of speculated reasons, such as higher rates of immunosuppressed individuals and possible climate. Due to clinician unfamiliarity, misdiagnosis of blastomycosis is common, which potentiates worsening systemic infections. This study shows the clinical course of a patient with blastomycosis in a non-endemic region, highlighting the need for education for clinicians in non-endemic areas. A 72-year-old female with a history of chronic obstructive pulmonary disease (COPD), coronary artery disease, a 47-year smoking history, and hypertension presented for outpatient management of COPD. CT three months prior to presentation showed nodular opacities in the lungs. A bronchoscopy was performed and revealed negative findings for malignancy or infection; the patient developed worsening symptoms leading to hospitalization. Subsequent testing revealed Blastomyces dermatitidis. She was promptly treated with a six to 12-month course of itraconazole with close follow-up. The study highlights the need not to rule out causes of infection based on location. Blastomycosis can resemble community-acquired pneumonia. Making the correct diagnosis is paramount, as delays can result in morbidity. Fungal cultures may be the gold standard, but due to the long culture time, there need to be other diagnostic tests like urine antigen testing. This study highlights the need to increase awareness of clinicians who experience blastomycosis patients in a non-endemic region.

Systemic immune inflammation index is associated with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

Background: In-stent neoatherosclerosis (ISNA) is identified as the primary cause of in-stent restenosis (ISR). The systemic immune inflammation index (SII), shows promise for predicting post-percutaneous coronary intervention (PCI) adverse cardiovascular events and is associated with coronary stenosis severity; however, its specific relationship with ISNA remains unclear. This study aimed to investigate the association between the SII and ISNA after drug-eluting stent (DES) implantation. Methods: This cross-sectional study included 195 participants with 195 ISR lesions who underwent optical coherence tomography (OCT)-guided PCI between August 2018 and October 2022. Participants were categorized based on the SII levels into Tertile 1 (SII <432.37, n = 65), Tertile 2 (432.37 ≤ SII ≤751.94, n = 65), and Tertile 3 (SII >751.94, n = 65). Baseline Clinical, angiographic, and OCT characteristics were analyzed. The association of the SII with ISNA and thin-fibroatheroma (TCFA) was investigated using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the SII in detecting ISNA and TCFA. Results: Patients in Tertile 3 had a significantly higher incidences of ISNA and TCFA than did those in Tertile 1. Logistic regression analysis revealed the SII is an independent indicator of ISNA and TCFA in ISR lesions (P = 0.045 and P = 0.002, respectively). The areas under the ROC curves for ISNA and TCFA were 0.611 and 0.671, respectively. Conclusion: The SII is associated with ISNA and TCFA and may serve as an independent indicator in patients with ISR.

Unraveling wasp sensitization in a patient with systemic mastocytosis by CAP-inhibition assay.

Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity.

Deciphering the cellular and molecular landscapes of Wnt/ß-catenin signaling in mouse embryonic kidney development.

Background: The Wnt/ß-catenin signaling pathway is critical in kidney development, yet its specific effects on gene expression in different embryonic kidney cell types are not fully understood. Methods: Wnt/ß-catenin signaling was activated in mouse E12.5 kidneys in vitro using CHIR99021, with RNA sequencing performed afterward, and the results were compared to DMSO controls (dataset GSE131240). Differential gene expression in ureteric buds and cap mesenchyme following pathway activation (datasets GSE20325 and GSE39583) was analyzed. Single-cell RNA-seq data from the Mouse Cell Atlas was used to link differentially expressed genes (DEGs) with kidney cell types. ß-catenin ChIP-seq data (GSE39837) identified direct transcriptional targets. Results: Activation of Wnt/ß-catenin signaling led to 917 significant DEGs, including the upregulation of Notum and Apcdd1 and the downregulation of Crym and Six2. These DEGs were involved in kidney development and immune response. Single-cell analysis identified 787 DEGs across nineteen cell subtypes, with Macrophage_Apoe high cells showing the most pronounced enrichment of Wnt/ß-catenin-activated genes. Gene expression profiles in ureteric buds and cap mesenchyme differed significantly upon ß-catenin manipulation, with cap mesenchyme showing a unique set of DEGs. Analysis of ß-catenin ChIP-seq data revealed 221 potential direct targets, including Dpp6 and Fgf12. Conclusion: This study maps the complex gene expression driven by Wnt/ß-catenin signaling in embryonic kidney cell types. The identified DEGs and ß-catenin targets elucidate the molecular details of kidney development and the pathway's role in immune processes, providing a foundation for further research into Wnt/ß-catenin signaling in kidney development and disease.

Enhanced Plaque Stabilization Effects of Alirocumab　- Insights From Artificial Intelligence-Aided Optical Coherence Tomography Analysis of the Alirocumab for Thin-Cap Fibroatheroma in Patients With Coronary Artery Disease Estimated by Optical Coherence Tomography (ALTAIR) Study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors stabilize vulnerable plaque, reducing cardiovascular events. However, manual optical coherence tomography (OCT) analysis of drug efficacy is challenging because of signal attenuation within lipid plaques. METHODS AND RESULTS: Twenty-four patients with thin-cap fibroatheroma were prospectively enrolled and randomized to receive alirocumab (75 mg every 2 weeks) plus rosuvastatin (10 mg/day) or rosuvastatin (10 mg/day) alone. OCT images at baseline and 36 weeks were analyzed manually and with artificial intelligence (AI)-aided software. AI-aided OCT analysis showed significantly greater percentage changes in the alirocumab+rosuvastatin vs. rosuvastatin-alone group in fibrous cap thickness (FCT; median [interquartile range] 212.3% [140.5-253.5%] vs. 88.6% [63.0-119.6%]; P=0.006) and lipid volume (median [interquartile range] -30.8% [-51.8%, -16.6%] vs. -2.1% [-21.6%, 4.3%]; P=0.015). Interobserver reproducibility for changes in minimum FCT and lipid index was relatively low for manual analysis (interobserver intraclass correlation coefficient [ICC] 0.780 and 0.499, respectively), but high for AI-aided analysis (interobserver ICC 0.999 and 1.000, respectively). Agreements between manual and AI-aided OCT analyses of FCT and the lipid index were acceptable (concordance correlation coefficients 0.859 and 0.833, respectively). CONCLUSIONS: AI-aided OCT analysis objectively showed greater plaque stabilization of adding alirocumab to rosuvastatin. Our results highlight the benefits of a fully automated AI-assisted approach for assessing drug efficacy, offering greater objectivity in evaluating serial changes in plaque stability vs. conventional OCT assessment.

A Pilot Study in Adapting the Chronic Care Model to Address Shortage of Child and Adolescent Psychiatry.

There is a nationwide shortage of child and adolescent psychiatrists. This, combined with the mental health crisis caused by the coronavirus 2019 pandemic has lead to low access to care for many individuals. Child Psychiatry Access Programs have been developed to address this need, but we believe they are not sufficient to care for complex cases. We propose that the Chronic Care Model can address these issues by providing, more longitudinal and and faster access to mental health care for patients. Our pilot study had 50 children and adolescent participants in our clinic model, which included the use of trainees supervised by an attending. We found that the mean wait time to appointment with a child and adolescent psychiatrist was 13.54 ± 14.8 days, which is significantly shorter by that reported by other studies. We believe our model clinic may be helpful in a variety of settings and want to share it with other psychiatrists.

Electrochemical impedance spectroscopy unmasks high-risk atherosclerotic features in human coronary artery disease.

Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. In this single-center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm2) with a median fibrous cap thickness of 62 µm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm2 versus <1.75 mm2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 µm versus >65 µm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm2, fibrous cap thickness ≤65 µm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716-1.000) (p = .013), 0.852 (0.646-1.000) (p = .025), and 0.835 (0.577-1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573-0.962) (p = .035). EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation.

Overexpression of NUDT16L1 sustains proper function of mitochondria and leads to ferroptosis insensitivity in colorectal cancer.

Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge. In this study, we shed light on the role of ferroptosis in colorectal cancer and identified a novel ferroptosis repressor, NUDT16L1, that contributes to the ferroptosis insensitivity in this cancer type. Mechanistically, NUDT16L1 promotes ferroptosis insensitivity in colon cancer by enhancing the expression of key ferroptosis repressor and mitochondrial genes through direct binding to NAD-capped RNAs and the indirect action of MALAT1. Our findings also reveal that NUDT16L1 localizes to the mitochondria to maintain its proper function by preventing mitochondrial DNA leakage after treatment of ferroptosis inducer in colon cancer cells. Importantly, our orthotopic injection and Nudt16l1 transgenic mouse models of colon cancer demonstrated the critical role of NUDT16L1 in promoting tumor growth. Moreover, clinical specimens revealed that NUDT16L1 was overexpressed in colorectal cancer, indicating its potential as a therapeutic target. Finally, our study shows the therapeutic potential of a NUDT16L1 inhibitor in vitro, in vivo and ex vivo. Taken together, these findings provide new insights into the crucial role of NUDT16L1 in colorectal cancer and highlight its potential as a promising therapeutic target.

The P(III)-amidite based synthesis of stable isotope labeled mRNA-cap-structures enables their sensitive quantitation from brain tissue.

The 5' cap structure is crucial to mRNA function, with its diverse methylation patterns depending on the cellular state. Sensitive analytical methods are sought after to quantify this cap variety also referred to as cap epitranscriptome. To address a bottleneck for accurate and precise quantitation, we report a facile and fast access to high-quality synthetic standards via a new route, involving P(III)-amidite chemistry. A range of cap nucleotides and their stable heavy isotopic labeled analogues were derived from nucleoside diphosphates, which themselves were directly prepared in a one-step reaction sequence starting from unprotected nucleosides using a triphosphorylating reagent in combination with ethylenediamine. Considering a wider scope, the route also enables direct access to magic spot nucleotides and diphosphates of isoprenyl-alcohols. Stable-isotope labeled cap nucleotides derived from this route paved the way for the development of a highly sensitive LC-MS/MS method, applied to the characterization of mouse brain cap epitranscriptomes, which turned out to be very different from those of cultured cell lines of widespread use in the life sciences.

Determination of the combined effect of grape seed extract and cold atmospheric plasma on foodborne pathogens and their environmental stress knockout mutants.

The study aimed to explore the antimicrobial efficacy of grape seed extract (GSE) and cold atmospheric plasma (CAP) individually or in combination against L. monocytogenes and E. coli wild type (WT) and their isogenic mutants in environmental stress genes. More specifically, we examined the effects of 1% (wt/vol) GSE, 4 min of CAP treatment, and their combined effect on L. monocytogenes 10403S WT and its isogenic mutants ΔsigB, ΔgadD1, ΔgadD2, ΔgadD3, as well as E. coli K12 and its isogenic mutants ΔrpoS, ΔoxyR, and ΔdnaK. In addition, the sequence of the combined treatments was tested. A synergistic effect was achieved for all L. monocytogenes strains when exposure to GSE was followed by CAP treatment. However, the same effect was observed against E. coli strains, only for the reversed treatment sequence. Additionally, L. monocytogenes ΔsigB was more sensitive to the individual GSE and the combined GSE/CAP treatment, whereas ΔgadD2 was more sensitive to CAP, as compared to the rest of the mutants under study. Individual GSE exposure was unable to inhibit E. coli strains, and individual CAP treatment resulted in higher inactivation of E. coli in comparison to L. monocytogenes with the strain ΔrpoS appearing the most sensitive among all studied strains. Our findings provide a step toward a better understanding of the mechanisms playing a role in the tolerance/sensitivity of our model Gram-positive and Gram-negative bacteria toward GSE, CAP, and their combination. Therefore, our results contribute to the development of more effective and targeted antimicrobial strategies for sustainable decontamination.IMPORTANCEAlternative approaches to conventional sterilization are gaining interest from the food industry, driven by (i) the consumer demand for minimally processed products and (ii) the need for sustainable, environmentally friendly processing interventions. However, as such alternative approaches are milder than conventional heat sterilization, bacterial pathogens might not be entirely killed by them, which means that they could survive and grow, causing food contamination and health hazards. In this manuscript, we performed a systematic study of the impact of antimicrobials derived from fruit industry waste (grape seed extract) and cold atmospheric plasma on the inactivation/killing as well as the damage of bacterial pathogens and their genetically modified counterparts, for genes linked to the response to environmental stress. Our work provides insights into genes that could be responsible for the bacterial capability to resist/survive those novel treatments, therefore, contributing to the development of more effective and targeted antimicrobial strategies for sustainable decontamination.

Differential culprit plaque morphology in acute coronary syndrome: a comparison between very young patients (≤35 years) and older counterparts using optical coherence tomography.

Aims: Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT. Methods and results: This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P < 0.001) groups. Conclusion: Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.

The Uncommon Suspect: Pseudomonas aeruginosa and Cavitary Lung Lesions in an Immunocompetent Patient.

Cavitary lung lesions pose a formidable diagnostic challenge due to their multifaceted etiologies. While tuberculosis and other prevalent pathogens typically dominate discussions, instances of community-acquired Pseudomonas aeruginosa (P. aeruginosa) pneumonia leading to cavitation in immunocompetent individuals remain exceptionally rare. Herein, we present a compelling case of such pneumonia in a 61-year-old man with a past medical history of hypertension and coronary artery disease who presented with cough, chest pain, and subjective fever. Chest imaging revealed cavitary lung lesions, which is atypical for community-acquired pneumonia (CAP). Initial workup excluded common CAP pathogens, following which bronchoscopy with bronchoalveolar lavage (BAL) definitively diagnosed P. aeruginosa, prompting targeted antibiotic therapy. Treatment led to clinical and radiographic improvement. P. aeruginosa rarely causes CAP, especially in immunocompetent patients, and cavitary lesions further complicate diagnosis. This case highlights the importance of considering P. aeruginosa in CAP with unusual features and emphasizes the utility of bronchoscopy with BAL for diagnosis and guiding management.

Cryo-EM structure of the CBC-ALYREF complex.

In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5' end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5' end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.

Sex differences in plaque characteristics of fractional flow reserve-negative non-culprit lesions after myocardial infarction.

BACKGROUND AND AIMS: Recurrent events after myocardial infarction (MI) are common and often originate from native non-culprit (NC) lesions that are non-flow limiting. These lesions consequently pose as targets to improve long-term outcome. It is, however, largely unknown whether these lesions differ between sexes. The aim of this study was to assess such potential differences. METHODS: From the PECTUS-obs study, we assessed sex-related differences in plaque characteristics of fractional flow reserve (FFR)-negative intermediate NC lesions in 420 MI-patients. RESULTS: Among the included patients, 80 (19.1 %) were female and 340 (80.9 %) male. Women were older and more frequently had hypertension and diabetes. In total, 494 NC lesions were analyzed. After adjustment for clinical characteristics and accounting for within-patients clustering, lesion length was longer in female patients (20.8 ± 10.0 vs 18.3 ± 8.5 mm, p = 0.048) and minimum lumen area (2.30 ± 1.42 vs 2.78 ± 1.54 mm2, p < 0.001) and minimum lumen diameter (1.39 ± 0.45 vs 1.54 ± 0.44 mm, p < 0.001) were smaller. The minimum fibrous cap thickness was smaller among females (96 ± 53 vs 112 ± 72 µm, p = 0.025), with more lesions harboring a thin cap fibroatheroma (39.3 % vs 24.9 %, p < 0.001). Major adverse cardiovascular events at two years occurred in 6.3 % of female patients and 11.8 % of male patients (p = 0.15). CONCLUSIONS: FFR-negative NC lesions after MI harbored more high-risk plaque features in female patients. Although this did not translate into an excess of recurrent events in female patients in this modestly sized cohort, it remains to be investigated whether this difference affects clinical outcome.

Interaction between product strategy selection and the carbon quota allocation policy.

The interaction between the government's carbon reduction policy and a firm's product strategy has not been well studied in the literature. This paper considers the government's two different carbon quota allocation policies for the cap-and-trade scheme and the firm's two product strategies and investigates the interaction between them by establishing a theoretical model and deriving the optimal decisions. This paper first examines the firms' selection of low-carbon products or ordinary product strategies under the government's two carbon quota allocation policies and then studies the government's optimal carbon quota allocation policy for overall social welfare, which is based on the firm's two product strategies. Our analysis reveals that (i) when the government allocates carbon quotas aimed at reducing the firm's total carbon emissions, the firm will choose the low-carbon product strategy. When the government allocates a carbon quota aimed at optimal total social welfare, the firm's decision depends on the impact of total carbon emissions. (ii) To achieve optimal social welfare, the government will formulate different carbon quota allocation policies on the basis of firms' different product strategies.