Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation.

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.

Platelet collagen receptors and their role in modulating platelet adhesion patterns and activation on alternatively processed collagen substrates.

This study examines the roles of platelet collagen receptors glycoprotein VI (GPVI), α2ß1, and the GPIb-IX-V complex in platelet activation and thrombus formation on various collagen sources from different species. Type I collagens standardly used in haematology testing, i.e. collagen type I derived from equine tendon (HORM) and rat tail collagen were evaluated. Moreover, acid soluble collagen from human umbilical cord was tested. To inhibit platelet-collagen interactions, combinations of monoclonal antibodies 6B4 and 6F1, targeting GPIbα and α2ß1, respectively, were used, along with the therapeutic collagen receptor GPVI antibody glenzocimab. Our findings reveal distinct dependencies on these receptors: platelet aggregation of washed platelets to HORM collagen relied on both α2ß1 and GPVI, to acid soluble collagen mainly on GPVI, and to rat tail collagen solely on α2ß1, respectively. In whole blood perfusion assays under non-coagulating conditions, the acid soluble collagen surface triggered a more homogenous platelet adhesion when compared to the HORM collagen surface, whilst platelet adhesion on rat tail collagen varied considerably. The GPIb-IX-V complex was shown to play a key role in initial platelet adhesion and activation across all collagen surfaces at a shear rate of 1600 s-1. At 1600 s-1, inhibiting platelet α2ß1 interaction with collagen by 6F1 antibody did not affect platelet thrombus formation on acid soluble collagen, while it did reduce platelet surface coverage and P-selectin expression on HORM collagen without changing the overall thrombus morphology or contraction. Inhibiting GPVI interaction with collagen significantly reduced all thrombus parameters and abolished PS exposure and P-selectin expression on all three collagen surfaces, at both 1600 s-1 and 150 s-1. Interestingly, upon investigating combined inhibition of GPIb and α2ß1, an additive inhibitor effect of 6F1 was observed on P-selectin expression and PS-exposure on acid soluble collagen but not HORM collagen at 1600s-1, suggesting that the acid soluble collagen is well suited to study reinforcing functions of collagen receptors. Overall, this study highlights the potential advantages of using alternative collagen surfaces beyond the conventional HORM collagen to detect nuanced collagen receptor dependencies, which may prove valuable in evaluating anti-platelet medication.

Epigenetic signatures of asthma: a comprehensive study of DNA methylation and clinical markers.

BACKGROUND: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. METHODS: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. RESULTS: 221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81. CONCLUSION: We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma.

Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles.

The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by delivering gene cargos that boost the levels of naturally produced antimicrobial peptides. The Cathelicidin Antimicrobial Peptide gene (CAMP), which produces the antimicrobial peptide LL-37, was used as model gene cargo. In vitro evaluation showed successful transfection and an increase in the transcription and translation of CAMP-coding plasmid in mouse primary epithelial cells. Moreover, we found that the extracellular vesicles (EVs) derived from the transfected cells (in vitro and in vivo) carried significantly higher concentrations of CAMP transcripts and LL-37 peptide compared to control EVs, possibly mediating the trafficking of the antimicrobial contents to other neighboring cells. The TNT platform was then used in vivo on an excisional wound model in mice to nanotransfect the CAMP-coding plasmid on the edge of infected wounds. After 4 days of daily treatment, we observed a significant decrease in the bacterial load in the CAMP-treated group compared to the sham group. Moreover, histological analysis and bacterial load quantification also revealed that TNT of CAMP on S. aureus-infected wounds was effective in treating biofilm progression by reducing the bacterial load. Lastly, we observed a significant increase in macrophage recruitment to the infected tissue, a robust increase in vascularization, as well as and an increased expression of IL10 and Fli1. Our results demonstrate that TNT-based delivery of gene cargos coding for antimicrobial compounds to the wound is a promising approach for combating biofilm infections in wounds.

The Relationship between History of Traumatic Brain Injury and Longitudinal Changes in Cortical Thickness among Patients with Alzheimer's Disease.

BACKGROUND: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD). METHODS: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness. RESULTS: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI. CONCLUSION: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions.

Chirality and odd mechanics in active columnar phases.

Chiral active materials display odd dynamical effects in both their elastic and viscous responses. We show that the most symmetric mesophase with 2D odd elasticity in three dimensions is chiral, polar, and columnar, with 2D translational order in the plane perpendicular to the columns and no elastic restoring force for their relative sliding. We derive its hydrodynamic equations from those of a chiral active variant of model H. The most striking prediction of the odd dynamics is two distinct types of column oscillation whose frequencies do not vanish at zero wavenumber. In addition, activity leads to a buckling instability coming from the generic force-dipole active stress analogous to the mechanical Helfrich-Hurault instability in passive materials, while the chiral torque-dipole active stress fundamentally modifies the instability by the selection of helical column undulations.

Maternal depressed mood and serotonergic antidepressant treatment during pregnancy differentially shape the continuity between fetal-newborn neurobehaviour.

BACKGROUND: Prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure is associated with newborn neurobehavioural disturbances, but it remains unclear whether this reflects a transient pharmacologic condition or an altered neurodevelopmental trajectory emerging in utero from sustained gestational SRI exposure. AIM: This study explored longitudinal relationships between third-trimester fetal physiology and newborn neurobehaviour, and determined whether early neurobehavioural continuity is shaped by prenatal SRI or depression exposure. METHODS: Participants were 127 pregnant mothers and their fetal-newborn offspring. Four groups were defined based on antenatal depressive symptoms and SRI treatment: Control (n = 51), Depressed (unmedicated; n = 35), SRI-Depressed (n = 26) and SRI-Non-Depressed (n = 15). Doppler measures of fetal heart rate (fHR), motor activity and vascular hemodynamics were obtained at 36-weeks' gestation, then newborn neurobehavioural maturity was evaluated at postnatal day-7. Partial least squares analysis was used to identify latent correlations between fetal-newborn measures; associations were further studied with hierarchical regression testing group moderation. RESULTS: Two dimensions described 74% of the covariance between fetal physiologic and newborn neurobehavioural measures (permuted p < 0.05). Three latent fetal-newborn relationships were significantly moderated by group: (1) lower fHR variability, and (2) greater fHR decelerations, predicted lower alertness/orientation scores but only in SRI-Depressed-group newborns; and (3) lower fetal cerebrovascular resistance predicted lower motor scores in Depressed-group newborns. SRI treatment to euthymia was not associated with fetal-newborn neurobehavioural disturbances. CONCLUSIONS: Maternal depression, both unmedicated and SRI-treated with persistent/poorly-managed mood symptoms, differentially shaped fetal-newborn neurobehavioural continuity. These findings suggest that neurobehavioural disturbances may predate birth, and underscore the importance of effective mental health management during pregnancy.

[Update on HPV-associated head and neck cancers-highlights of the 2024 ASCO Annual Meeting]. / Update zu HPV-assoziierten Kopf-Hals-Karzinomen ­ Highlights der ASCO-Jahrestagung 2024.

BACKGROUND: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), a large number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented. OBJECTIVE: Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided. METHODS: The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts. RESULTS AND CONCLUSION: A large number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from a phase I study on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to a reduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as a breakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP.

Hospitalized patients on proton pump inhibitors for stress ulcer prophylaxis have a higher risk of Clostridioides difficile infection compared with those on histamine-2 receptor antagonists.

BACKGROUND: Previous studies on Clostridioides difficile infection (CDI) in proton pump inhibitor (PPI) users generally enrolled a heterogeneous population and did not include a control group of histamine H2 receptor antagonists (H2RAs) users or adjust for confounding variables, such as previous antibiotics. It is uncertain whether hospitalized patients using PPIs for stress ulcer prophylaxis (SUP) are at a higher risk of CDI compared with those using H2RAs. This study aimed to compare the association between CDI and the usage of antisecretory drugs (ASDs): PPIs and H2RAs, for SUP among hospitalized patients, and the impact of the duration of their use on CDI. METHODS: In this nationwide population-based cohort study using the Taiwan National Health Insurance Database, hospitalized patients using ASDs for SUP were identified between 2017 and 2018. A total of 63,266 and 69,269 individuals were included in the PPI and H2RA groups, respectively. The primary endpoint was a 90-day monitoring of CDI occurrence. FINDINGS: The incidences of CDI were 1.6/10,000 and 0.5/10,000 person-days in the PPIs and H2RAs groups, respectively. After adjusting for confounding factors, the risk of infection in the PPIs group remained significantly higher than in the H2RAs group (hazard ratio (HR), 2.49; 95% confidence interval (CI), 1.63-3.81). In the subgroup analysis, during hospitalization, the risk of CDI for patients using high-risk antibiotics or admitted to the intensive care unit (ICU), as well as patients with immunodeficiency, using PPIs for SUP, was higher than using H2RAs. Furthermore, the risk of CDI was higher in patients using ASDs for durations >14 days than in those using them for <7 days (adjusted HR, 3.66; 95% CI, 2.34-5.75). CONCLUSIONS: The risk of occurrence CDI for hospitalized patients using PPIs for SUP was higher than using H2RAs. It is recommended not to exceed 14 days of any gastric ASDs for SUP during hospitalization, especially for patients who have used high-risk antibiotics, have been admitted to the ICU, or have immunodeficiency.

Association of ambient air pollution with cognitive functioning and markers of structural brain damage: The Maastricht study.

INTRODUCTION: Given the absence of curative interventions and the rising global incidence of dementia, research is increasingly focusing on lifestyle factors for prevention. However, identifying shared environmental risk for dementia, next to individual factors, is crucial for optimal risk reduction strategies. Therefore, in the present study we investigated the association between air pollution, cognitive functioning, and markers of structural brain damage. METHODS: We used cross-sectional data from 4,002 participants of The Maastricht Study on volumetric markers of brain integrity (white and grey matter volume, cerebrospinal fluid volume, white matter hyperintensities volume, presence of cerebral small vessel disease) and cognitive functioning (memory, executive functioning and attention, processing speed, overall cognition). Individuals were matched by postal code of residence to nationwide data on air pollution exposure (particulate matter < 2.5 µm (PM2.5), particulate matter <10 µm (PM10), nitrogen dioxide (NO2), soot). Potentia linear and non-linear associations were investigated with linear, logistic, and restricted cubic splines regression. All analyses were adjusted for demographic characteristics and a compound score of modifiable dementia risk and protective factors. RESULTS: Exposure to air pollutants was not related to cognitive functioning and most brain markers. We found curvilinear relationships between high PM2.5 exposures and grey matter and cerebrospinal fluid volume. Participants in the low and high range of exposure had lower grey matter volume. Higher cerebrospinal fluid volumes were only associated with high range of exposure, independent of demographic and individual modifiable dementia risk factors. After additional post hoc analyses, controlling for urbanicity, the associations for grey matter volume became non-significant. In men only, higher exposure to all air pollutants was associated with lower white matter volumes. No significant associations with white matter hyperintensities volume or cerebral small vessel disease were observed. DISCUSSION: Our findings suggest that higher PM2.5 exposure is associated with more brain atrophy.

[Clinical efficacy of dorsal venous complex pre-suture technique in the robot-assisted laparoscopic radical prostatectomy].

The clinical data of 33 patients who underwent robot-assisted laparoscopic Vattikuti Institute prostatectomy (VIP) in Cancer Hospital of Chinese Academy of Medical Sciences from October 2020 to April 2022 were reviewed and analyzed. Among them, 18 patients received traditional VIP technique and 15 patients received VIP technique with pre-sutured dorsal venous complex (DVC). The ages of the traditional VIP group and the pre-sutured DVC VIP group were (66.1±7.3) and (66.6±5.7) years, respectively. The body mass index (BMI) of the traditional VIP group and the pre-sutured DVC VIP group was (24.3±2.9) and (25.3±2.6) kg/m2, respectively. The medical expenses were (91 797.0±7 029.6) and (87 106.6±7 031.4) yuan, respectively, with no statistical significance (all P>0.05). The operations of all the 33 cases were successfully completed, and no cases were transferred to open surgery. The operation time of traditional VIP group was longer than that of pre-sutured DVC VIP group [(193.0±37.2) vs (171.1±16.1) min]. The amount of intraoperative blood loss was higher than that in the pre-sutured DVC VIP group [(68.3±22.8) vs (44.0±9.1) ml)], all P<0.05. No patients had perioperative blood transfusion, and no patients had complications within 30 days after surgery. All the 33 patients had negative incisal margins. DVC presuture technique can reduce intraoperative bleeding and shorten operative time in robot-assisted laparoscopic VIP radical prostatectomy, and has good curative effect.

Effect of Dopant Concentration on Luminescence Properties of Na3Ca2(SO4)3F: RE (RE = Eu3+, Dy3+) Phosphor for Solid-State Lighting.

A fluoride material phosphor doped with rare earth ions Eu3+ and Dy3+ was studied for its photoluminescence (PL) properties. The material was synthesized using a combustion method and characterized using X-ray diffraction (XRD) and PL techniques. The Na3Ca2(SO4)3F: Eu3+ phosphor exhibits two distinct peaks at 593 nm (orange) and 615 nm (red) at an excitation wavelength of 395 nm. The PL excitation spectrum of the Na3Ca2(SO4)3F: Dy3+ phosphor showed series of peaks, corresponding to the 4f → 4f transitions of Dy3+ ions. Under 350-nm excitation, the PL emission spectrum revealed two prominent bands one at 483 nm (blue region) due to the 4F9/2 → 6H15/2 transition, and another at 573 nm (yellow region) resulting from the 4F9/2 → 6H13/2 transition. These blue and yellow emissions suggest potential applications in solid-state lighting, particularly for mercury-free excitation sources. Rare earth-doped Eu3+/Dy3+ materials exhibit highly efficient PL properties, making them suitable candidates for white light-emitting diodes (LEDs) or other solid-state lighting phosphors.

Examining the quantum fisher information in the interaction of a dirac system with a squeezed generalized amplitude damping channel.

The inherent association between real quantum systems and their surrounding environment invariably results in decoherence, leading to the loss of entanglement. This diminution in entanglement coincides with a decline in the fidelity of transmitted information using the entangled quantum resource. This study scrutinizes the impact of the squeezed generalized amplitude damping (SGAD) channel on quantum Fisher information (QFI) parameters. The SGAD channel model, a versatile framework, is also employed to simulate other dissipative channels, including amplitude damping (AD) and generalized amplitude damping (GAD). Kraus operators facilitate the modeling of noisy channels. The results reveal that, within the SGAD channel, the QFI remains impervious to the squeezing variables (r and Φ ). In the GAD channel, F θ GAD undergoes enhancement to a constant value with an upswing in temperature (T), while the ϕ parameter in the GAD channel, F ϕ GAD , akin to the SGAD channel, surges around T = 2 before complete loss ensues. Concerning the AD channel, the θ component of the QFI initially experiences decoherence with an augmentation in the AD noise parameter ( λ ). Subsequently, it is restored to its initial value with a further escalation in λ . Conversely, the ϕ component of the QFI in the AD channel experiences decoherence with an elevation in the AD noise parameter ( λ ).

Mid-gap levels induced near-infrared response and photothermal catalytic degradation of chlortetracycline hydrochloride by (SnFe2)Ox under solar light.

We present a comprehensive photocurrent characterization to explore the near-infrared (NIR) response and photothermal effects induced by mid-gap levels in (SnFe2)Ox (SFO) nanoparticles. X-ray photoelectron spectroscopy and diffuse reflectance spectroscopy revealed multiple mid-gap levels due to multivalent Fe ions. The SFO photocatalyst displayed a noticeable temperature rise under NIR irradiation and a considerable photothermal effect across the full solar spectrum during the photocatalytic degradation of chlortetracycline hydrochloride (CTC·HCl). In photothermal catalysis, after 150 min, SFO was able to remove 88% of CTC·HCl (60 mg/L), outperforming photocatalysis (79%) and thermal catalysis (73%). Rapid and slow response processes were observed in the photocurrent characterization under light-emitting diodes of different wavelengths (365-1500 nm), which revealed a clear dependence on the incident wavelength. Furthermore, innovative photocurrent response tests using alternating ultraviolet (UV) and NIR irradiation revealed that, in the presence of mid-gap levels, UV-excited electrons can aid NIR-excited electrons in achieving cascaded electron transitions, enhancing the utilization of NIR-excited electrons. Our findings demonstrate that mid-gap levels effectively improve the utilization of low-energy photons and boost the photocatalytic process through photothermal effects and increased active charge carrier density.

Laser-driven electron source suitable for single-shot Gy-scale irradiation of biological cells at dose rates exceeding 10

We report on the first systematic characterization of a tuneable laser-driven electron source capable of delivering Gy-scale doses in a duration of 10-20 ps in a single irradiation, thus reaching unprecedented dose rates in the range of 10^{10}-10^{12} Gy/s. Detailed characterization of the source indicates, in agreement with Monte Carlo simulations, dose delivery over cm-scale areas with a high degree of spatial uniformity. The results reported here confirm that a laser-driven source of this kind can be used for systematic studies of the response of biological cells to picosecond-scale radiation at ultrahigh dose rates.

[Trend of incidence rate of acute myocardial infarction in Tengzhou City, Shandong Province, from 2013 to 2021].

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 (Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant (χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas (Z=-8.529 and -11.235, both P<0.001).

[Bidirectional causal relationship between glucose-lipid metabolism, obesity indicators, and myocardial infarction: a bidirectional Mendelian randomization analysis study].

Objective: To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis. Methods: Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran's Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results: Higher BMI (OR=1.070, 95%CI: 1.041-1.100), waist-to-hip ratio (OR=1.366, 95%CI: 1.113-1.677), LDL-C (OR=1.638, 95%CI: 1.488-1.803), triglycerides (OR=1.445, 95%CI: 1.300-1.606), waist circumference (OR=1.841, 95%CI: 1.650-2.055), hip circumference (OR=1.247, 95%CI: 1.132-1.372), body fat percentage (OR=1.795, 95%CI: 1.568-2.055), whole-body fat mass (OR=1.519, 95%CI: 1.381-1.670), trunk fat percentage (OR=1.538, 95%CI: 1.374-1.723), and trunk fat mass (OR=1.421, 95%CI: 1.294-1.561), as well as lower HDL-C (OR=0.799, 95%CI: 0.729-0.875), have causal effects on myocardial infarction (all P<0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio (OR=1.457, 95%CI: 1.132-1.877), fasting glucose (OR=1.191, 95%CI: 1.024-1.383), glycated hemoglobin (OR=1.129, 95%CI: 1.034-1.233), LDL-C (OR=1.592, 95%CI: 1.314-1.929), triglycerides (OR=1.410, 95%CI: 1.279-1.553), waist circumference (OR=1.922, 95%CI: 1.448-2.551), body fat percentage (OR=1.421, 95%CI: 1.072-1.884), and whole-body fat mass (OR=1.295, 95%CI: 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C (OR=0.809, 95%CI: 0.729-0.897) remained negatively associated. Conclusions: Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.

Alternatives to surveillance for persistent human papillomavirus after a positive cervical screen: A systematic review and meta-analysis.

OBJECTIVES: In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression. METHODS: We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool. RESULTS: 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance. CONCLUSION: This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance.

Marine plastic pollution: A systematic review of management strategies through a macroscope approach.

Alternatives to address the ocean plastic crisis have been a hot topic in scientific literature, although a systemic approach to assess their effectiveness and identify bottlenecks is still lacking. To contribute to discussions on this topic, this study aims to conduct a literature review on current scientific information regarding management strategies for marine plastic pollution. The PRISMA method was used to select the most relevant articles from the Scopus® database, resulting in a sample of 176 articles after applying exclusion criteria for full-text evaluation. Unlike other literature review studies, Odum's Macroscope is used here to develop a model that provides a systemic view of the plastic crisis on a large scale, encompassing various compartments and their interactions. Specifically, eight compartments are identified: industry, consumers, waste collection & management, freshwater systems, fisheries, aquaculture and shipping, marine ecosystems, marine plastic collection and recycling, and life cycle. Each piece of literature reviewed is categorized into one of these compartments and discussed accordingly. The highlights of the results indicate that: (i) waste collection & management and freshwater systems, which are primary pathways for plastic litter reaching the ocean, have been relatively under-investigated compared to other compartments. (ii) Most studies originate from developed countries, raising doubts about the effectiveness of management proposals in underdeveloped countries. (ii) Existing strategies for collecting and recycling marine litter are unlikely to be implemented at a large scale due to operational obstacles, thus offering insufficient mitigation for the plastic crisis. (iv) The development of new biomaterials has proven mostly ineffective and harmful. (v) Alternatives management for microplastic pollution are still in their infancy, resulting in scarce information across all compartments. (vi) No studies focus on the origin of the plastic issue, which lies in the petrochemical industry. From a general perspective, the literature indicates that there is no one-size-fits-all management strategy to the plastic crisis, and the available options are often scattered and disconnected, making a systemic approach essential for studying such a transboundary issue. While efforts exist, stakeholders must act to effectively address the problem, or at least make meaningful progress. The marine plastic crisis operates systemically, analogous to the climate crisis, both stemming from human dependence on fossil fuels. Similar to achieving carbon neutrality, designing a globally sustainable economy should prioritize achieving plastic neutrality as a core component.

Access to prior screening mammograms affects the specificity but not sensitivity of radiologists' performance.

AIMS: To establish the impact that access to prior mammograms has on radiologists' performance and the influence of radiologists' characteristics and breast density on their subsequent performance. METHODS: Eight participants independently interpreted 72 digital screening mammograms in two reading sessions using the Royal Australian and New Zealand College of Radiologist's classification. In the first reading session, participants were given access to current and prior mammograms. In the second reading session six months later, participants only had access to the current mammograms. Radiologists' specificity, sensitivity, lesion sensitivity, Receiver Operating Characteristic (ROC) curve, and Jacknife Alternative Free-response ROC (JAFROC) were calculated. A Paired T-test was used to compare readings with and without prior mammograms, and to assess if breast density influenced participants performance. Independent Sample T-test was used to compare performance across radiologists' characteristics. A relative risk analysis was conducted to assess the probability of false positives and false negatives when prior mammograms were available. RESULTS: Access to prior mammograms improved specificity in dense and non-dense breasts (p≤0.01) and reduced false positives (p = 0.01) but had no effect on sensitivity (p = 0.37), lesion sensitivity (p = 0.67), ROC (p = 0.16), and JAFROC (p = 0.24). Prior mammogram also reduced the probability of false positives (RR = 0.38; 95%CI:0.26-0.57, p<0.0001) without affecting the false negative rate (RR = 1.14; 95%CI:0.88-1.49, p = 0.30). The impact of prior mammograms on performance was not influenced by breast density or radiologists' characteristics. CONCLUSIONS: Access to prior mammograms improves radiologists' specificity and reduces false positives without affecting sensitivity and the false negative rate regardless of radiologists' characteristics and breast density.