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Abstract Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include: • CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT). • D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed. • Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding. • Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase. • On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation. • Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death. • Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis. • Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen–progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used. • Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum. Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations. This article is an abridged translation of the German guideline, which is available online.

By utilizing progress in millijoule-level pulsed fiber lasers operating in the 1.96 µm spectral range, we introduce a concept utilizing a spaceborne differential absorption barometric lidar designed to operate within the 1.96 µm CO2 absorption band for remote sensing of Martian atmospheric properties. Our focus is on the online wavelength situated in the trough region of two absorption lines, selected due to its insensitivity to laser frequency variations, thus mitigating the necessity for stringent laser frequency stability. Our investigation revolves around a compact lidar configuration, featuring reduced telescope dimensions and lower laser pulse energies. These adjustments are geared towards minimizing costs for potential forthcoming Mars missions. The core measurement objectives encompass the determination of column CO2 absorption optical depth, columnar CO2 abundance, surface atmospheric pressure, and vertical distributions of dust and cloud layers. Through the amalgamation of surface pressure data with atmospheric temperature insights garnered from sounders and utilizing the barometric formula, the prospect of deducing atmospheric pressure profiles becomes feasible. Simulation studies validate the viability of our approach. Notably, the precision of Martian surface pressure measurements is projected to surpass 1 Pa when the aerial dust optical depth is projected to be under 0.7, a typical airborne dust scenario on Mars, considering a horizontal averaging span of 10 km.

Abstract Increasing evidence demonstrates the psychological benefits of nature contact. However, the evidence is often established at the population level, and the individual differences in the psychological benefits gained from nature are considered negligible variations. In this study, we performed a cross-sectional online survey in Brisbane and Sydney, Australia, from April 15th and May 15th, 2021 around one year after the first covid-19 pandemic lockdowns. The results show that individuals with a stronger connection to nature are linked with a lower level of stress and anxiety with increased frequency in public greenspace visits, while such an association is less clear for individuals with a weaker connection to nature. We also find that, through the answer to an open-ended question, individuals with a lower connection to nature tend to mention nature-related words less as the reason for visiting greenspace. This indicates that a person’s connection to nature is linked with how they interact with nature and thus might determine whether and how much psychological benefit a person gains from experiencing nature.

Purpose: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies. Design: Experimental study. Subjects: Biospecimens from patients with active or inactive uveitis and healthy controls. Methods: Protein concentration and single cell gene expression were assessed in aqueous fluid biopsies and plasma samples from deidentified patients with uveitis or healthy controls. Main Outcome Measures: The concentration of 31 inflammatory proteins was measured in all aqueous samples, as well as plasma samples from patients with active uveitis. Chemokine and cytokine ligand and receptor expression were assessed in individual cell types from aqueous biopsies obtained from patients with active uveitis. Results: We identified 6 chemokines that were both elevated in active uveitis compared with controls and enriched in aqueous compared with plasma during active uveitis (C-C motif chemokine ligand [CCL]2, C-X-C motif chemokine ligand [CXCL]10, CXCL9, CXCL8, CCL3, and CCL14), forming potential gradients for migration of immune cells from the blood to the eye. Of these, CCL2 and CXCL10 were consistently enriched in the aqueous of all patients in our cohort, as well as in a larger cohort of patients from a previously published study. These data suggest that CCL2 and CXCL10 are key mediators in immune cell migration to the eye during uveitis. Next, single cell RNA sequencing suggested that macrophages contribute to aqueous enrichment of CCL2 and CXCL10 during human uveitis. Finally, using chemokine ligand and receptor expression mapping, we identified a broad signaling network for macrophage-derived CCL2 and CXCL10 in human uveitis. Conclusions: These data suggest that ocular macrophages may play a central role, via CCL2 and CXCL10 production, in recruiting inflammatory cells to the eye in patients with uveitis. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined. The purpose of this study was to identify transcriptional signatures of circulating immune cells that are associated with high anti-VEGF treatment burden. Design: Experimental pilot study. Participants: Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System. Methods: We profiled by single cell RNA sequencing the peripheral blood mononuclear cells of 27 treatment-experienced patients with wet AMD. We stratified this cohort into 2 groups with low and high treatment burden (≤ 5 or ≥ 6 injections in the past 12 months, respectively). Main Outcome Measures: Identification of immune cells associated with high treatment burden. Results: Gene expression signature of CD16+ monocytes may be associated with high treatment burden. Conclusions: These studies delineate potential signatures of circulating immune cells that may be associated with high treatment burden in neovascular AMD, potentially informing the development of diagnostic predictors of anti-VEGF response and new precision medicine-based approaches to complement anti-VEGF therapies. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Topic: Though lipid and cholesterol dyshomeostasis is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), there is no consensus regarding which elements of systemic lipid homeostasis are perturbed in AMD. In this systematic review and meta-analysis, an update to that performed by Wang et al in 2016, we characterized serum lipoprotein profiles in patients with AMD and its various stages. Clinical Relevance: These findings may identify novel therapeutic approaches for AMD, a leading cause of blindness among older adults in the industrialized world. Methods: We used MEDLINE, Embase, and Web of Science to identify articles from database inception to May 2022 that reported blood/serum levels of lipid subspecies (triglycerides [TGs], total cholesterol [TC], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) in patients with AMD compared with controls. We meta-analyzed the data by generating multilevel random-effects models using restricted maximum likelihood estimation. Results: Our updated meta-analysis included 56 studies, almost 3 times as many studies as the 2016 meta-analysis with a total of 308 188 participants. There were no significant differences in serum TG, TC, LDL, or HDL between patients with AMD and non-AMD controls. Given significant heterogeneity, we performed subanalyses specifically in patients with early to intermediate nonexudative AMD, advanced nonexudative AMD, and advanced exudative AMD. Compared with non-AMD controls, patients with early to intermediate nonexudative AMD had significantly lower serum TG (standardized mean difference [SMD]: −0.03; 95% confidence interval [95% CI]: −0.06 to −0.01) and higher serum HDL (SMD: 0.07; 95% CI: 0.04–0.11). Patients with advanced exudative AMD had significantly higher serum LDL (SMD: 0.33; 95% CI: 0.04–0.62) compared with non-AMD controls. There were no other significant differences identified. Conclusion: We found that there is significant heterogeneity in systemic lipoproteins in patients with AMD compared with non-AMD controls. The specific pattern of lipid dyshomeostasis appeared to be distinct based on AMD stage. These findings highlight both the underlying heterogeneity of AMD as well as the presence of distinct pathophysiological mechanisms involved at different stages or subtypes of AMD and may inform the development of novel therapeutic approaches. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hexabromocyclododecane (HBCD)-containing waste was co-disposed in a cement kiln to evaluate its destruction removal efficiency (DRE) and its impact on polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) formation. The DRE of HBCD exceeded 99.9999 %. The residual HBCD after disposal was mainly found in kiln head ash and clinker. Stack gas at kiln head and tail exhibited average PBDD/Fs emission levels (sum of 13 2,3,7,8-PBDD/Fs congeners) of 0.36 and 0.42 ng m -3 , respectively, with octa-BDD predominating. However, in the kiln tail ash, hexaBDF and hepta-BDF were secondarily generated, leading to an increase in PBDFs concentration. Notably, most HBCD underwent debromination and ring-opening in the calciner, with released bromine absorbed and removed by CaO. Its decomposition products such as polycyclic aromatic hydrocarbons, biphenyls and their derivatives served as carbon sources for PBDD/Fs synthesis. However, co-disposal of HBCD did not significantly raise PBDD/Fs emissions but altered their homolog distribution from PBDDs to PBDFs. Emission factors of HBCD and PBDD/Fs were the highest in the clinker at 6.55 × 10 2 and 0.55 × 10 2  μg t -1 , respectively. Therefore, attention was needed for the potential secondary release of pollutants during the transportation and utilization of clinker. These findings enhanced understanding of the distribution and formation pathways of PBDD/Fs during cement kiln co-processing, providing insights for their source control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plasticity, a key hallmark of cancer, enables cells to transition into different states, driving tumor heterogeneity. This cellular plasticity is associated with cancer progression, treatment resistance, and relapse. Cancer stem cells (CSCs) play a central role in this process, yet the molecular factors underlying cancer cell stemness remain poorly understood. In this study, we explored the role of XIST (X-inactive specific transcript) long noncoding RNA in ovarian cancer stemness and plasticity through in silico and in vitro analyses. We found that XIST is significantly down-regulated in ovarian tumors, with low XIST expression linked to a higher stemness index and lower overall survival. Knocking down XIST in ovarian cancer cells enhanced stemness, particularly increasing mesenchymal-like CSCs, and under hypoxic conditions, it promoted epithelial-like CSC markers. Our findings suggest that XIST loss leads to CSC enrichment and cellular plasticity in ovarian cancer, pointing to potential therapeutic targets for patients with low XIST expression., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: CAR-T-cell therapy and bispecific antibody have revolutionized the treatment landscape for multiple myeloma. However, there is currently a lack of studies comparing the efficacy and safety of these two approaches. This meta-analysis assesses the efficacy and safety of B-cell maturation antigen (BCMA)-directed CAR-T-cell therapies and BCMA×CD3 bispecific antibodies as third-line or later interventions for relapsed/refractory multiple myeloma (RRMM)., Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases up to May 31, 2024, identifying 11 eligible studies encompassing 1269 participants. Random-effects models evaluated the primary (complete response (CR) rate) and secondary (overall response rate (ORR)) outcomes, while meta-regression analyses adjusted for relevant covariates., Results: CAR-T-cell therapy achieved significantly higher pooled CR rate (0.54 (95% CI 0.42-0.69) vs bispecific antibodies 0.35 (0.30-0.41), p<0.01) and pooled ORR (0.83 (0.76-0.90) vs 0.65 (0.59-0.71), p<0.01). However, CAR-T therapy had a higher incidence of adverse events, particularly cytokine release syndrome (CRS 0.83 (0.70-0.97) vs bispecific antibodies 0.59 (0.43-0.74), p<0.05). Severe CRS (grade ≥3) occurred at a rate of 0.07 (0.03-0.14) in the CAR-T cell group, contrasting with a negligible rate of 0.01 (0.00-0.02) in the bispecific antibody group (p<0.01). Hematologic adverse events, including neutropenia (grade ≥3; 0.88 (0.81-0.95) vs 0.48 (0.30-0.67), p<0.01) and anemia (grade≥3; 0.55 (0.47-0.62) vs 0.34 (0.28 to 0.40), p<0.01), were also more frequent in the CAR-T-cell group. Furthermore, differences in efficacy were observed among various CAR-T products, with ciltacabtagene autoleucel showing greater efficacy in CR rate (0.77 (0.71-0.84) vs 0.37 (0.32-0.41), p<0.01) and ORR (0.91 (0.83-0.99) vs 0.73 (0.68-0.77), p<0.01) compared with idecabtagene vicleucel., Conclusion: CAR-T-cell therapy demonstrated superior CR rates compared with bispecific antibodies, although with an increase in severe adverse events., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Urban composite non-point source (UCNPS) has an increasing degree of influence on the urban receiving waters. However, there remains a dearth of precise techniques to characterize and evaluate the contribution of UCNPS. Therefore, this study developed a source analytical methodology system based fluorescence excitation-emission matrices spectroscopy (EEMs) and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS).Specifically, it utilized parallel factor analysis (PARAFAC), two-dimensional correlation spectroscopy (2D-COS), end-member mixing analysis (EMMA), and non-metric multidimensional scaling (NMDS) to analysis UCNPS pollution characteristics and quantify its contributions to river DOM. The results of its application in typical hilly and plain urban within the Yangtze River Basin, China revealed that road and roof runoff exhibited high aromaticity and humic-like content, and the characteristics of pipe sediment was similar with domestic sewage. The component of Rivers had sequences of changes under rainfall perturbations. But terrestrial humic-like represented the initial input in all cases, and it can provide some indication of UCNPS input. The results of EMMA showed that the contribution of road runoff, roof runoff, pipeline sediment and domestic sewage to river DOM was 9.0 %-36.0 %, 2.6 %-19.1 %, 2.3 %-28.8 % and 5.9 %-25.9 %, respectively, and the specific contribution was mainly affected by rainfall level, regional terrain and drainage system. The methodology system of this study can provide technical support for the traceability and precise control of UCNPS pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Microplastics, pervasive contaminants from plastic, present significant challenges to wastewater treatment processes. This review critically examines the interactions between microplastics and biofilm-based treatment technologies, specifically focusing on the concepts of "biofilm on microplastics" and "microplastics in biofilm". It discusses the implications of these interactions in contaminant removal and process performance. Advanced characterization techniques, including morphological characterization, chemical composition analysis, and bio-information analysis, are assessed to elucidate the complex interplay between microplastics and biofilms within biofilters, biological aerated filters (BAFs), rotating biological contactors (RBCs), and moving bed biofilm reactors (MBBRs). This review synthesizes current research findings, highlighting that microplastics can either hinder or enhance the treatment processes, contingent on their concentration, physicochemical properties, and the specific biofilm technology employed. The insights gained from this review are essential for developing strategies to mitigate the adverse effects of microplastics and for optimizing the design and operation of wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A series of 3,7 a -diazacyclohepta[ jk ]fluorene derivatives were synthesized via a gold(I)-catalyzed 6- exo - dig hydroamination/7- endo - dig cycloisomerization domino method. The method exhibits a broad substrate scope, and a plausible mechanism has been proposed. The efficacy of this strategy is further validated by the successful derivatization of 3,7 a -diazacyclohepta[ jk ]fluorene.

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Endothelial cells are the first and most damaged target cells during acute lung injury (ALI). Endothelial dysfunction increases pulmonary microvascular permeability, subsequently leading to pulmonary oedema and organ dysfunction; however, clinical treatments against microvascular permeability show poor efficacy. Herein, we aimed to explore the role of the Sigma-1 receptor (Sig-1R) in pulmonary microvascular permeability by constructing ALI animal and cell models, and further investigated the specific mechanisms., Methods: The effects of Sig-1R on lung injury and endothelial barrier disruption were examined in lipopolysaccharide (LPS)-induced mice and human umbilical vein endothelial cells (HUVECs), respectively. Transcriptome sequencing was carried out to identify possible targets of Sig-1R, and the specific mechanisms of Sig-1R action were investigated using RNA interference and plasmid transfection., Results: Analysis of a Gene expression omnibus dataset suggested that Sig-1R plays a protective role against vascular hyperpermeability in ALI. Downregulation of Sig-1R expression and endothelial barrier disruption were both observed in mice and HUVECs upon LPS stimulation. Sig-1R agonists attenuated vascular hyperpermeability in vivo and in vitro, further improving ALI. Sig-1R activation downregulated Leucine-rich repeat kinase 2 (LRRK2) expression in mice and HUVECs. LRRK2 knockdown ameliorated endothelial barrier disruption in mice and HUVECs. Overexpression of LRRK2 reversed the protective effect of Sig-1R activation on LPS-induced endothelial hyperpermeability. Furthermore, Sig1r knockdown exacerbated LPS-induced microvascular hyperpermeability, which was rescued by inhibition of LRRK2., Conclusions: Sig-1R activation exerts a protective effect against LPS-induced microvascular hyperpermeability by downregulating LRRK2 expression, which could lead to the development of novel therapeutic strategies for treating ALI., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2024. Published by Elsevier Inc.)

Calcium oscillations in primary neuronal cultures and iPSCs have been employed to investigate arrhythmogenicity and epileptogenicity in drug development. Previous studies have demonstrated that Ca 2+ influx via NMDA and nicotinic acetylcholine receptors (nAChRs) modulates Ca 2+ oscillations. Nevertheless, there has been no comprehensive investigation into the impact of ischemia or nAChR-positive allosteric modulators (PAM) drugs on Ca 2+ oscillations at a level that would facilitate high-throughput screening. We investigated the effects of ischemia and nAChR subtypes or nAChR PAM agonists on Ca 2+ oscillations in high-density 2D and 3D-sphere primary neuronal cultures using 384-well plates with FDSS-7000. Ischemia for 1 and 2 h resulted in an increase in the frequency of Ca 2+ oscillations and a decrease in their amplitude in a time-dependent manner. The NMDA and AMPA receptor inhibition significantly suppressed Ca 2+ oscillation. Inhibition of NR2A or NR2B had the opposite effect on Ca oscillations. The potentiation of ischemia-induced Ca 2+ oscillations was significantly inhibited by the NMDA receptor antagonist, MK-801, and the frequency of these oscillations was suppressed by the NR2B inhibitor, Ro-256981. In the 3D-neurosphere, the application of an α7nAChR agonist increased the frequency of Ca 2+ oscillations, whereas the activation of α4β2 had no effect. The combination of nicotine and PNU-120596 (type II PAM) affected the frequency and amplitude of Ca 2+ oscillations in a manner distinct from that of type I PAM. These systems may be useful not only for detecting epileptogenicity but also in the search for neuroprotective agents against cerebral ischemia., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval All experiments were performed following the Use of Laboratory Animals and ARRIVE guidelines. The Institutional Animal Care and Use Committee of Osaka University Graduate School of Medicine approved all animal protocols and experiments (Permission number: 30-091-001, 05-078-0000). Consent for publication All authors give their consent and approval for publication of this manuscript., (© 2024. The Author(s).)

Objective: To investigate the effectiveness and safety of exercise rehabilitation in older adults undergoing intervention for heart valve disease., Method: PubMed, Embase, Cochrane Library, CINAHL, Ovid Medline, SPORTDiscus, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang were systematically searched until January 2024. Risk-of-bias assessments were performed using the Cochrane risk-of-bias tool. A meta-analysis of the following indexes was performed using RevMan 5.4 software., Results: Nine trials involving 631 patients were ultimately included. Exercise rehabilitation significantly reduced the risk of adverse events, increased the 6-minute walk distance, improved the physical component of quality of life, and shortened the length of postoperative hospitalization. However, exercise rehabilitation did not affect all-cause mortality, left heart ejection fraction, or peak oxygen uptake., Conclusions: Exercise rehabilitation may enhance exercise capacity, reduce the incidence of adverse events, and shorten the length of postoperative hospitalization in older adults undergoing intervention for heart valve disease., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patellar fractures, in particular inferior pole fractures, pose significant challenges due to the patella's complex biomechanics and crucial role in knee extension and stability. This study aimed to compare the therapeutic effectiveness and long-term efficacy of two fixation methods: combined vertical wire and mini steel plate fixation versus independent vertical wire fixation. The comparison was based on clinical classification, addressing the ongoing debate regarding optimal management strategies for patellar inferior pole fractures., Methods: A retrospective cohort study was conducted, analyzing 226 patients with patellar inferior pole fractures. Patients were divided into two groups: the independent vertical wire fixation group (n = 117) and the combined vertical wire and mini steel plate fixation group (n = 109). Demographic data, clinical characteristics, surgical outcomes, functional outcomes, pain levels, return to daily activities, quality of life, and both short-term and long-term complications were assessed and compared between the two groups., Results: The combined fixation group demonstrated significantly superior surgical outcomes, including shorter operation times and lower infection rates, despite higher blood loss. Furthermore, this group exhibited enhanced functional outcomes, reduced pain levels, and lower rates of osteoarthritis and salvage procedures compared with the independent fixation group., Conclusions: The findings of this study suggest potential advantages of combined vertical wire and mini steel plate fixation over independent vertical wire fixation in the treatment of patellar inferior pole fractures. The combined fixation method was associated with improved surgical outcomes, enhanced functional recovery, better pain management, and reduced long-term complication rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Three-dimensional (3D) bioprinting technology stands out as a promising tissue manufacturing process to control the geometry precisely with cell-loaded bioinks. However, the isotropic culture environment within the bioink and the lack of topographical cues impede the formation of oriented cardiac tissue. To overcome this limitation, we present a novel method named 3D nanofiber-assisted embedded bioprinting (3D-NFEP) to fabricate cardiac tissue with an oriented morphology. Aligned 3D nanofiber scaffolds were fabricated by divergence electrospinning, which provided structural support for printing of the low-viscosity bioink and structural induction to cardiomyocytes. Cells adhered to the aligned fibers after hydrogel degradation, and a high degree of cell alignment was observed. This technology was also demonstrated as a feasible solution for multilayer cell printing. Therefore, 3D-NFEP was demonstrated as a promising method for bioprinting oriented cardiac tissue with low-viscosity bioink and is expected to be applied for structured and cardiac tissue engineering.

The increased prevalence of opioid use disorder (OUD) makes it imperative to disentangle the biological mechanisms contributing to individual differences in OUD vulnerability. OUD shows strong heritability, however genetic variants contributing toward vulnerability remain poorly defined. We performed a genome-wide association study using over 850 male and female heterogeneous stock (HS) rats to identify genes underlying behaviors associated with OUD such as nociception, as well as heroin-taking, extinction and seeking behaviors. By using an animal model of OUD, we were able to identify genetic variants associated with distinct OUD behaviors while maintaining a uniform environment, an experimental design not easily achieved in humans. Furthermore, we used a novel non-linear network-based clustering approach to characterize rats based on OUD vulnerability to assess genetic variants associated with OUD susceptibility. Our findings confirm the heritability of several OUD-like behaviors, including OUD susceptibility. Additionally, several genetic variants associated with nociceptive threshold prior to heroin experience, heroin consumption, escalation of intake, and motivation to obtain heroin were identified. Tom1, a microglial component, was implicated for nociception. Several genes involved in dopaminergic signaling, neuroplasticity and substance use disorders, including Brwd1, Pcp4, Phb1l2 and Mmp15 were implicated for the heroin traits. Additionally, an OUD vulnerable phenotype was associated with genetic variants for consumption and break point, suggesting a specific genetic contribution for OUD-like traits contributing to vulnerability. Together, these findings identify novel genetic markers related to the susceptibility to OUD-relevant behaviors in HS rats.

To assess the inherent effects of light-dark cycle on the aniline degradation and nitrogen removal in algal-bacterial symbiotic system, three groups with different photoperiods (0L:12D;6L:6D;12L:0D) were set up. The results revealed that the aniline degradation rate of the three systems all surpassed 99 %, the total nitrogen removal rate of Z2-6L:6D was approximately 36 % higher than Z1-0L:12D eventually, the Z1-0L:12D was restrained by NH 4 + -N assimilation and nitrification while anoxic denitrification in Z3-12L:0D. The disappearance of microalgae biomass was accompanied by the sharp decreased of polysaccharide in Z1 and longer illumination suppressed the secretion of extracellular polymeric substances, the Z3 yielded slightly superior biomass production despite the double illumination compared with Z2. Moreover, high throughput sequencing analysis illustrated that the microbial community structure in Z2 was more abundant and even than Z3, the TM7a, norank&#95;f&#95;&#95;norank&#95;o&#95;&#95;Saccharimonadales, Ellin6067 and Scenedesmus proliferated wildly and the photoinhibition to functional genus was effectively alleviated in Z2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Bronchopulmonary dysplasia (BPD) is a common morbidity in extremely premature infants. Previous studies demonstrated the important role of lysophosphatidic acid (LPA) in inflammation in BPD. However, the role of LPA and its receptors in hyperoxia-induced vascular malformations in BPD remains to be elucidated., Methods and Results: Elevated plasma LPA levels were observed in mice with BPD compared to controls (792 vs. 607 ng/mL, p < 0.05). Inhibition of LPA signaling protected against hyperoxia-induced lung injury in neonatal mice, demonstrated by a 2.8-fold increase in pulmonary vascular density and a 14% reduction in alveolar enlargement. In vitro studies showed that LPA suppressed tube formation in human umbilical vein endothelial cells (HUVECs) by approximately 50%. LPA receptor 2 (LPA 2 ) was identified as a functional LPA receptor in primary endothelial cells from the lungs of hyperoxic mice and in HUVECs under hyperoxic conditions. The LPA 2 antagonist H2L5186303 enhanced the tube formation ability of HUVECs exposed to LPA, both under normoxia (4-fold) and hyperoxia (5-fold). Moreover, H2L5186303 significantly protected against hyperoxia-induced vascular malformation (2-fold) and improved alveolarization in neonatal mice (12% decrease in mean linear intercept, MLI). Early growth response 1 (EGR1) was characterized as a downstream target of LPA 2 , silencing EGR1 restored tube formation in HUVECs exposed to LPA and hyperoxia., Conclusions: Our in vitro and in vivo findings demonstrate that the inhibition of LPA/LPA 2 signaling mitigates hyperoxia-induced pulmonary vascular malformations, suggesting the LPA/LPA 2 -dependent signaling pathway has therapeutic potential for extremely premature infants with BPD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Inflammation and coagulation cascades are closely correlated with cancer occurrence and progression. This study investigated the prognostic value of the combination of plasma fibrinogen level and neutrophil-to-lymphocyte ratio (F-NLR) in patients with upper tract urothelial carcinoma (UTUC). The predictive ability of the F-NLR for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) was initially established and then further validated in patients who underwent radical nephroureterectomy for UTUC. As a result, patients were divided into three groups following the establishment of cut-off values for the NLR (≥2.53 vs. <2.53) and fibrinogen (≥4.55 vs. <4.55) through receiver operating characteristic (ROC) curve analysis: F-NLR score 0 (low fibrinogen and low NLR), 2 (high fibrinogen and high NLR), or 1 (remaining patients). The F-NLR score was then identified as an independent risk factor for OS, CSS, and PFS (all P-value <0.05) by multivariate regression analysis in both the training and validation cohorts. In addition, F-NLR-based nomograms for OS, CSS, and PFS were developed and evaluated using the concordance index (C-index) and calibration curves. The integration of the F-NLR into existing nomograms improved predictive accuracy compared to the use of nomograms without the F-NLR score. This suggests that the addition of F-NLR is beneficial for enhancing the accuracy of prognosis prediction in patients with UTUC. The F-NLR score may serve as a powerful predictor for patients with UTUC.

Abstract: Sepsis-associated acute kidney injury (SAKI), a common complication in intensive care units (ICUs), is linked to high morbidity and mortality. Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, has been shown to have distinct effects on autophagy regulation compared to other sirtuins, but its role in SAKI remains unclear. This study explored the potential of SIRT2 as a therapeutic target for SAKI. We found that inhibition of SIRT2 with the antagonist AGK2 improved the survival of septic mice. SIRT2 inhibition reduced kidney injury, as indicated by lower levels of KIM-1, NGAL, serum creatinine (Scr), blood urea nitrogen (BUN), and proinflammatory cytokines following cecal ligation and puncture (CLP). Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells (RTECs) and upregulated LC3 II expression in the renal cortex. Consistent with in vivo findings, SIRT2 gene silencing promoted autophagy in LPS-treated HK-2 cells, whereas SIRT2 overexpression inhibited it. Mechanistically, SIRT2 inhibition increased FOXO1 acetylation, inducing its nuclear-to-cytoplasmic translocation, which promoted kidney autophagy and alleviated SAKI. Our study suggests SIRT2 as a potential target for SAKI therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Ethnopharmacological Relevance: The Huaxian formula (HXF), a traditional Chinese medicine (TCM) remedy, specifically targets the pathological factors of "heat toxicity" and "phlegm stasis" induced by radiation in radiation-induced pulmonary fibrosis (RIPF). It works by clearing heat and invigorating the blood, addressing these key factors in the development of RIPF., Aim of the Study: The HXF has demonstrated potential in preventing RIPF, although its underlying mechanisms remain unclear. This study aims to investigate the efficacy, molecular targets, and mechanisms of action of HXF., Materials and Methods: The major constituents of the HXF were identified by ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS). C57BL/6j mice were divided into four groups: control (Ctrl), HXF alone (HXF), 17Gy-irradiation alone (IR), and irradiation plus HXF (IR + HXF). Lung damage and fibrosis were assessed by histopathological staining, and the flow cytometry and immunohistochemistry (IHC) were used to detect the macrophages phenotype of lung tissues in vivo at 16 weeks post-irradiation. Transcriptomic sequencing and bioinformatics analyses identified key genes modulated by HXF. In vitro assays included flow cytometry, western bolt, and quantitative PCR (qPCR) explored the impact of HXF on macrophage polarization and fibrotic activity, while co-culture experiments of the macrophage conditional medium and mouse embryo fibroblast NIH/3T3 investigated macrophage-fibroblast interactions., Results: 20 major constituents of HXF were identified. And the in vivo results revealed significant lung damage and fibrosis in the IR group, which were notably mitigated in the IR + HXF group. And HXF has been shown to significantly inhibit the infiltration of M2-type macrophages in lung tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) such as Arg1, Mmp10, and Fgf23. Bioinformatics enrichment analysis indicated that these DEGs are involved in pathways related to the inhibition of extracellular matrix formation and inflammation. In vitro, HXF-containing serum reduced M2-type macrophage polarization and decreased the secretion of Arginase1 and TGFβ1. Conditioned medium from HXF-treated macrophages suppressed fibroblast activation., Conclusion: HXF's preventive effects on RIPF involve multiple targets and mechanisms, including the modulation of Arg1, Mmp10, and Fgf23 expression. By inhibiting the pro-fibrotic capacity of macrophages, HXF suppresses fibroblast activation and collagen production, thereby alleviating lung fibrosis. These findings underscore the potential of HXF as a preventive strategy in managing RIPF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection., Materials and Methods: We conducted a genome-wide association study of chronic P. aeruginosa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic P. aeruginosa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis., Results: Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10 -8 ) and rs927553 (chr13q12.12; p=1.91×10 -8 ) were associated with chronic P. aeruginosa infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic P. aeruginosa infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic P. aeruginosa infection age (β=0.782 years, p=4.24×10 -4 ). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012)., Conclusions: We identified two novel loci that are associated with chronic P. aeruginosa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between P. aeruginosa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Objectives: To test the effect of azithromycin in reducing bronchopulmonary dysplasia (BPD) risk in extremely preterm infants (EPI) without pulmonary infection., Study Design: A retrospective cohort study was performed in EPI in a tertiary unit from September 2018 to September 2022. Since only Ureaplasma species positive infants were treated with azithromycin, we included infants without Ureaplasma species (no azithromycin treatment) and those diagnosed with Ureaplasma species colonization (azithromycin treatment) in the study, while infants with Ureaplasma species pneumonia were excluded. The primary outcome was grade II + BPD, defined as BPD of grade II or higher according to the updated NICHD criteria (2018). Multiple logistic regression analysis was used to identify the independent association between grade II + BPD and azithromycin treatment., Results: A total of 237 EPIs were included in the current study, of which 202 infants were classified as no azithromycin treatment (Ureaplasma species negative) and 35 infants were classified as azithromycin treatment (Ureaplasma species colonization). Clinical characteristics were similar between groups. Infants treated with azithromycin had a significantly lower rate of grade II + BPD (8.6% vs. 31.2%, p = 0.006), and shorter duration of invasive ventilation (0 vs. 3 days, p = 0.045) compared to untreated ones. After adjusting for confounders, azithromycin treatment was significantly associated with reduced risk of grade II + BPD in the whole cohort (odd ratio [OR] 0.211, 95% CI: 0.056, 0.786, p = 0.020], and infants absent of other pulmonary infection (OR 0.115, 95% CI: 0.014, 0.979, p = 0.048)., Conclusion: Azithromycin is associated with a reduced risk of grade II + BPD in EPIs, likely due to its anti-inflammatory effect., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Anomalous X-ray diffraction (AXD) and neutron diffraction can be used to crystallographically distinguish between metals of similar electron density. Despite the use of AXD for structural characterization in mixed metal clusters, there are no benchmark studies evaluating the accuracy of AXD toward assessing elemental occupancy in molecules with comparisons with what is determined via neutron diffraction. We collected resonant diffraction data on several homo and heterometallic clusters and refined their anomalous scattering components to determine metal site occupancies. Theoretical resonant scattering terms for Fe 0 , Co 0 , and Zn 0 were compared against experimental values, revealing theoretical values are ill-suited to serve as references for occupancy determination. The cluster featuring distinct cation and anion metal compositions [CoCp 2 *][( tbs L)Fe 3 (μ 3 -NAr)] was used to assess the accuracy of different f ' references for occupancy determination ( f ' theoretical ± 15-17%; f ' experimental ± 10%). This methodology was applied toward calculating the occupancy of three different clusters: ( tbs L)Fe 2 Zn(py) ( 6 ), ( tbs L)Fe 2 Zn(μ 3 -NAr)(py) ( 7 ), and [CoCp* 2 ][( tbs L)Fe 2 Zn(μ 3 -NAr)] ( 8 ). The first two clusters maintain 100% Fe/Zn site isolation, whereas 8 showed metal mixing within the sites. The large crystal size of 8 enabled collection of neutron diffraction data which was compared against the results found with AXD. The ability of AXD to replicate the metal occupancies as determined by neutron diffraction supports the AXD occupancy methodology developed herein. Furthermore, the advantages innate to AXD (e.g., smaller crystal sizes, shorter collection times, and greater availability of synchrotron resources) versus neutron diffraction further support the need for its development as a standard technique.

Competing Interests: Declaration of interests JSJ reports grants and non-financial support from WHO, outside the submitted work. MW reports grants from the Wellcome Trust during the conduct of the study. All other authors declare no competing interests.

Transition metal phosphides (TMPs) with high electrocatalytic activity for the oxygen evolution reaction (OER) are reckoned as a substitution of precious group metals catalysts in rechargeable Zn-air battery. In this work, Co/Co 2 P heterojunction nanoparticles supported N,P-doped carbon nanosheets (Co/Co 2 P@NPCNS) were designed and prepared via a facile one-step molten salt-assisted pyrolysis process. Density function theory calculations reveal that the heterogeneous interactions of Co/Co 2 P effectively enhance the bifunctional electrocatalytic activity for oxygen reduction reaction (ORR) and OER. The synergistic interaction between the Co/Co 2 P heterojunction nanoparticles with highly exposed active sites and excellent catalytic activity and the two-dimensional doped carbon nanosheets with high conductivity contributes to Co/Co 2 P@NPCNS exhibiting preeminent bifunctional ORR/OER activity and stability with a high half-wave potential for ORR (0.87 V), a low overpotential for OER (302 mV at 10 mA cm -2 ) and a low potential gap (0.66 V). The homemade rechargeable Zn-air battery performs high peak power density (187 mW cm -2 ) and exceptional endurance. This heterogeneous interface tactic of integrating TMPs with heteroatom-doped carbon materials may shed light on the research and development of non-precious metal electrocatalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer.  Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition., (©2024 American Association for Cancer Research.)

Recurrence and metastasis stand as the primary contributors to mortality among patients with triple-negative breast cancer post-surgery, presenting a formidable clinical obstacle. Chemodynamic therapy (CDT), leveraging metal-ion-mediated Fenton-like reactions within the tumor microenvironment (TME), emerges as a promising avenue for addressing cancer metastasis. Despite recent progress, challenges such as tumor cell antioxidant defenses and epithelial-mesenchymal transition (EMT) impede the efficacy of CDT. Here, we introduce a novel approach using DNA-templated nanosheets (Dz-MnO 2 ) that combine the functions of Mn 2+ -mediated CDT and DNAzyme-mediated gene therapy to suppress tumor growth and metastasis. The Dz-MnO 2 nanosheets respond effectively to the TME, releasing Mn 2+ and DNAzyme. The DNAzyme exhibits mRNA cleavage activity, specifically targeting oncogenic transcripts to reduce tumor progression. Mn 2+ not only facilitates a Fenton-like reaction, enhancing the chemodynamic treatment effect, but also serves as a cofactor for DNAzyme, improving its catalytic efficiency. Concurrently, the nanosheets robustly silence the Twist1 gene, mitigating the EMT process and reinforcing CDT efficacy by suppressing apoptosis resistance. Results indicate that Dz-MnO 2 nanosheets efficiently polarize M2-tumor-associated macrophages (TAMs) into M1-TAMs by locally mitigating tumor hypoxia via catalyzing the decomposition of H 2 O 2 into O 2 . This collaborative strategy presents a promising approach to enhance CDT, effectively inhibiting tumor recurrence and metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP)., Methods: In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP)., Results: Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models., Conclusion: We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2024 Lin and Huang.)

Background: Horizontal semicircular canal benign paroxysmal positional vertigo(HSC-BPPV) is the second most common type of BPPV. It is difficult to diagnose and treat, which has a serious impact on the prognosis of patients., Objectives: To study the clinical features of HSC-BPPV and the influencing factors of residual dizziness (RD)., Materials and Methods: The clinical data of 358 patients with BPPV were retrospectively collected. The differences between HSC-BPPV and posterior semicircular canal benign paroxysmal positional vertigo (PSC-BPPV) were compared, and the influencing factors of RD after HSC-BPPV repositioning were analyzed., Results: ① Compared with PSC-BPPV, HSC-BPPV had a lower success rate of first repositioning (64.7 vs. 75.0%), a higher incidence of RD (57.3 vs. 43.8%), and a higher DHI score (40.0 vs. 34.0), and the differences were statistically significant ( p  < .05). ② Logistic regression analysis showed that age ≥60 years, secondary, DHI score, successful first repositioning were the influencing factors for the development of RD after HSC-BPPV repositioning ( p  < .05)., Conclusions and Significance: The diagnosis and treatment of HSC-BPPV is difficult, and RD is prone to occur. Clinicians need to strengthen the training of HSC-BPPV diagnosis and treatment to reduce the occurrence and progression of RD.

Background: Left ventricular (LV) mass is a well-established prognostic indicator for cardiovascular risk. Measurement of LV mass on coronary computed tomography angiography (CCTA) is considered optional. We aimed to assess for associations between LV mass measured on CCTA with all-cause mortality (ACM) risk and to determine age- and sex-specific distributions., Methods: We evaluated patients without known coronary artery disease (CAD) who underwent CCTA at a single center. We assessed age- and sex-specific distributions (10th, 25th, 50th, 75th, and 90th percentiles) of LV mass index. ACM, the primary endpoint, was recorded over a median period of 5.1 [interquartile range: 1.4-8.4] years. The association between LV mass and mortality risk was assessed using multivariable Cox models adjusted for age, sex, medical history, coronary artery calcium (CAC) score and CCTA stenosis., Results: 4187 patients (mean age: 61.9 ​± ​11.7, 63 ​% male) were included. Male sex, African American ethnicity, Hypertension, CAC>400, and smoking were independent predictors of increased LV mass index. During the median 5.1 years of study follow, 265 (6.3 ​%) deaths occurred. Increased LV mass index percentiles were associated with increased risk of ACM. The addition of LV mass index percentiles improved discrimination and reclassification for mortality prediction over a model with age, sex, conventional risk factors, CAC score and CCTA stenosis severity (X 2 improvement: 22.68, NRI: 28 ​%, both p ​< ​0.001)., Conclusion: In a large sample of patients without known CAD who underwent CCTA, increased LV mass index provided independent and incremental prognostic value for all-cause mortality. Assessment of LV mass by CCTA, considering age and gender distribution, can be utilized clinically to identify patients with high myocardial mass., Competing Interests: Declaration of competing interest All authors declare no relevant conflicts of interest related to the study., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

In the context of carbon neutrality, reducing electricity consumption is an inevitable requirement for sustainable development in China. It is of practical significance to understand the role of fiscal decentralization (FD) in energy conservation and emission reduction of local governments. This paper uses panel data of 30 provinces from 2004 to 2020 to build panel fixed effect, mediating effect and moderating effect models, and empirically analyzes the impact of Chinese-style FD on electricity consumption. The results find that FD significantly increases electricity consumption, but there is obvious heterogeneity. Infrastructure construction, industrial development and scale economies are the influencing channels through which FD affects electricity consumption. At the same time, marketization development is conducive to alleviating the promoting effect of FD on electricity consumption, but inter-governmental investment competition may strengthen the influence of FD. Moreover, as electricity demand rises, the impact of FD will intensify. Therefore, the research results of this paper highlight the importance of green fiscal reform., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 hr/daily). We analyzed individual differences in escalation of intake, progressive ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors., Competing Interests: Gd, LC, MK, MB, BB, LM, DC, SS, LT, MF, AM, NV, DO, BS, JR, JL, JK, AK, SS, LS, KS, SB, ES, AA, SP, JM, CC, LC, AV, KM, PS, BL, BP, AC, OP, LS, AP, OG No competing interests declared, (© 2023, de Guglielmo, Carrette et al.)

Co-disposal of hexabromocyclododecane (HBCD)-containing waste during municipal solid waste incineration (MSWI) was conducted, achieving a destruction efficiency exceeding 99.999%. Simultaneous determination of HBCD, polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) at multiple stages of a MSWI plant was performed. This aimed to clarify their concentration and congener variations along the flue, with the goal of elucidating their formation mechanisms and control. This study confirmed that HBCD was present in daily MSW, and that PBDEs and PBDD/Fs can be unintentionally produced. The average mass emission factors of HBCD, PBDEs, and PBDD/Fs from stack gas were 6.4 ± 5.0, 98.8 ± 4.6, and 2.8 ± 1.7 μg t -1 , respectively. HBCD and PBDEs were much higher in slag, raising concerns about the secondary release of brominated pollutants during the reprocessing or reuse of incinerator slag. The concentrations of PBDEs and PBDD/Fs increased after the air pollution control devices, largely due to the "memory effect", with regenerated PBDD/Fs being mainly high-brominated homologs. The disposal of HBCD increased PBDEs concentration and altered PBDD/F homolog distribution. Possible formation pathways of PBDEs and PBDD/Fs from HBCD were proposed. HBCD could degraded into brominated short-chain hydrocarbons and aromatic fragments, which may promote the formation of PBDEs and PBDD/Fs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Environmental management literature suggests that elevating the total factor productivity (TFP) of the renewable energy (RE) industry is pivotal for achieving green development. With intensifying market competition in the RE sector, collaborative innovation (COI) has emerged as a crucial strategic choice for enterprises to address developmental bottlenecks. To assess the potential of COI in driving green development, we leveraged data from 114 Chinese RE enterprises from 2011 to 2022. The research findings indicate: (1) COI significantly enhances the TFP of RE enterprises; this enhancement primarily stems from the positive influence of COI on innovation capabilities. (2) The positive effects of COI on TFP manifest only when market competition surpasses a certain threshold level. (3) COI significantly impacts the TFP of small and medium-sized RE enterprises in the growth stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Carbon labeling (CL) is a carbon reduction policy with development potential that has not yet been widely promoted worldwide. This study explores the trend of consumers' willingness to pay (WTP) for different types of carbon-labeled products from a dynamic perspective, to provide a reference for future pilot projects. The research team collected 3788 valid questionnaires from China's first-tier cities spanning a five-year period and used interval regression to analyze the impact and change of consumer traits on WTP for the four types of carbon-labeled products in 2019 and 2024. The bootstrap method was further used to examine the impact mechanisms to explore ways to improve the current situation. This study found that (1) WTP for food, textiles, electronics, and other household products with CL generally decreased from 2019 to 2024. Textiles and electronics experienced a smaller decline, while food and other household products witnessed larger decreases. (2) The effect of consumer characteristics on WTP changes from 2019 to 2024. Consumers' frequency of low-carbon behaviors no longer significantly affects WTP across all product categories, while attitudes toward CL only affect textiles and electronics. (3) Consumers' perceived environmental value is the mechanism by which personal traits affect WTP. Finally, based on the findings, this study suggests that the selection of textiles and electronics as a pilot product is more likely to be accepted by consumers and that emphasis should be placed on the promotion of the environmental values of CL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Large language models (LLMs) have shown promising performance in various healthcare domains, but their effectiveness in identifying specific clinical conditions in real medical records is less explored. This study evaluates LLMs for detecting signs of cognitive decline in real electronic health record (EHR) clinical notes, comparing their error profiles with traditional models. The insights gained will inform strategies for performance enhancement., Methods: This study, conducted at Mass General Brigham in Boston, MA, analysed clinical notes from the four years prior to a 2019 diagnosis of mild cognitive impairment in patients aged 50 and older. We developed prompts for two LLMs, Llama 2 and GPT-4, on Health Insurance Portability and Accountability Act (HIPAA)-compliant cloud-computing platforms using multiple approaches (e.g., hard prompting, retrieval augmented generation, and error analysis-based instructions) to select the optimal LLM-based method. Baseline models included a hierarchical attention-based neural network and XGBoost. Subsequently, we constructed an ensemble of the three models using a majority vote approach. Confusion-matrix-based scores were used for model evaluation., Findings: We used a randomly annotated sample of 4949 note sections from 1969 patients (women: 1046 [53.1%]; age: mean, 76.0 [SD, 13.3] years), filtered with keywords related to cognitive functions, for model development. For testing, a random annotated sample of 1996 note sections from 1161 patients (women: 619 [53.3%]; age: mean, 76.5 [SD, 10.2] years) without keyword filtering was utilised. GPT-4 demonstrated superior accuracy and efficiency compared to Llama 2, but did not outperform traditional models. The ensemble model outperformed the individual models in terms of all evaluation metrics with statistical significance (p < 0.01), achieving a precision of 90.2% [95% CI: 81.9%-96.8%], a recall of 94.2% [95% CI: 87.9%-98.7%], and an F1-score of 92.1% [95% CI: 86.8%-96.4%]. Notably, the ensemble model showed a significant improvement in precision, increasing from a range of 70%-79% to above 90%, compared to the best-performing single model. Error analysis revealed that 63 samples were incorrectly predicted by at least one model; however, only 2 cases (3.2%) were mutual errors across all models, indicating diverse error profiles among them., Interpretation: LLMs and traditional machine learning models trained using local EHR data exhibited diverse error profiles. The ensemble of these models was found to be complementary, enhancing diagnostic performance. Future research should investigate integrating LLMs with smaller, localised models and incorporating medical data and domain knowledge to enhance performance on specific tasks., Funding: This research was supported by the National Institute on Aging grants (R44AG081006, R01AG080429) and National Library of Medicine grant (R01LM014239)., Competing Interests: Declaration of interests None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study provides new insights into the causal relationship between implementing Emission Trading Schemes (ETS) and corporate behaviors related to Environmental, Social, and Governance (ESG) greenwashing from 2009 to 2022. Utilizing a concise empirical framework, our findings substantiate the catalytic role of China's ETS in reducing ESG greenwashing activities. However, the effectiveness of this mitigation varies depending on firm's size, governance quality, and pollution nature. Notably, the impact of the ETS also differs based on cohort, calendar times, and exposure duration. Furthermore, our analysis explores the complex mechanisms through which ETS influences ESG greenwashing across four key dimensions, revealing that factors like innovation (including R&D and green innovation) and supply chain dynamics enhance the scheme's ability to curb greenwashing. Conversely, financial constraints and the digital divide can undermine the effectiveness of China's ETS, potentially leading to increased greenwashing practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The repair of DNA double-strand breaks (DSBs) through homologous recombination (HR) is vital for maintaining the stability and integrity of the genome. RNA binding proteins (RBPs) intricately regulate the DNA damage repair process, yet the precise molecular mechanisms underlying their function remain incompletely understood. In this study, we highlight the pivotal role of RPS15, a representative RBP, in homologous recombination repair. Specifically, we demonstrate that RPS15 promotes DNA end resection, a crucial step in homologous recombination. Notably, we identify an interaction between RPS15 and CtIP, a key factor in homologous recombination repair. This interaction is essential for CtIP recruitment to DSB sites, subsequent RPA coating, and RAD51 replacement, all critical steps in efficient homologous recombination repair and conferring resistance to genotoxic treatments. Functionally, suppressing RPS15 expression sensitizes cancer cells to X-ray radiation and enhances the therapeutic synergistic effect of PARP1 inhibitors in breast cancer cells. In summary, our findings reveal that RPS15 promotes DNA end resection to ensure effective homologous recombination repair, suggesting its potential as a therapeutic target in cancer treatment., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Efforts toward developing wound dressings that effectively monitor healing have become at the forefront of the field of wound healing. However, monofunctionality, biotoxicity, and passive therapy constrain wound patches. Herein, a hypoallergenic wound patch integrating moisture monitoring, motion sensing and electrical stimulation for wound healing is presented. Microstructured patches composed of silk proteins and spider silk proteins (MIS) fused together were structurally transformed and crosslinked by spin-coating a mixture of silk proteins (SFs) and spider silk proteins (SPs) with water-soluble polyurethane (PU), creating MIS patches with microstructures by hot embossing. This is attributed to stable SF-SP hydrogen bonding, which provides an extremely rapid response to humidity and endows the patch with superior motion sensing tensile properties. Notably, β-folding and α-helical structures confer SP toughness and strength, producing electrical charges under electrical stimulation occurring with motor stretching, thereby enabling electrical stimulation for quicker wound healing. Specifically, The MIS is sensitive to changes in humidity, which is reflected in changes in the colour of its surface patches. Also it enhances the strength of the electrical stimulation signal more effectively as the thickness of the film layer increases. These characteristics indicate the high potential of the MIS for wound management., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Integrating artificial intelligence (AI) in healthcare settings has the potential to benefit clinical decision-making. Addressing challenges such as ensuring trustworthiness, mitigating bias, and maintaining safety is paramount. The lack of established methodologies for pre- and post-deployment evaluation of AI tools regarding crucial attributes such as transparency, performance monitoring, and adverse event reporting makes this situation challenging., Objectives: This paper aims to make practical suggestions for creating methods, rules, and guidelines to ensure that the development, testing, supervision, and use of AI in clinical decision support (CDS) systems are done well and safely for patients., Materials and Methods: In May 2023, the Division of Clinical Informatics at Beth Israel Deaconess Medical Center and the American Medical Informatics Association co-sponsored a working group on AI in healthcare. In August 2023, there were 4 webinars on AI topics and a 2-day workshop in September 2023 for consensus-building. The event included over 200 industry stakeholders, including clinicians, software developers, academics, ethicists, attorneys, government policy experts, scientists, and patients. The goal was to identify challenges associated with the trusted use of AI-enabled CDS in medical practice. Key issues were identified, and solutions were proposed through qualitative analysis and a 4-month iterative consensus process., Results: Our work culminated in several key recommendations: (1) building safe and trustworthy systems; (2) developing validation, verification, and certification processes for AI-CDS systems; (3) providing a means of safety monitoring and reporting at the national level; and (4) ensuring that appropriate documentation and end-user training are provided., Discussion: AI-enabled Clinical Decision Support (AI-CDS) systems promise to revolutionize healthcare decision-making, necessitating a comprehensive framework for their development, implementation, and regulation that emphasizes trustworthiness, transparency, and safety. This framework encompasses various aspects including model training, explainability, validation, certification, monitoring, and continuous evaluation, while also addressing challenges such as data privacy, fairness, and the need for regulatory oversight to ensure responsible integration of AI into clinical workflow., Conclusions: Achieving responsible AI-CDS systems requires a collective effort from many healthcare stakeholders. This involves implementing robust safety, monitoring, and transparency measures while fostering innovation. Future steps include testing and piloting proposed trust mechanisms, such as safety reporting protocols, and establishing best practice guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Emerging diagnostic scenarios, such as population surveillance by pooled testing and on-site rapid diagnosis, highlight the importance of advanced microfluidic systems for in vitro diagnostics. However, the widespread adoption of microfluidic technology faces challenges due to the lack of standardized design paradigms, posing difficulties in managing macro-micro fluidic interfaces, reagent storage, and complex macrofluidic operations. This paper introduces a novel modular-based mesoscopic design paradigm, featuring a core "needle-plug/piston" structure with versatile variants for complex fluidic operations. These structures can be easily coupled with various microfluidic platforms to achieve truly self-contained microsystems. Incorporated into a "3D extensible" design architecture, the mesoscopic design meets the demands of function integration, macrofluid manipulations, and flexible throughputs for point-of-care nucleic acid testing. Using this approach, an ultra-sensitive nucleic acid detection system is developed with a limit of detection of ten copies of SARS-CoV-2 per mL. This system efficiently conducts large-scale pooled testing from 50 pharyngeal swabs in a tube with an uncompromised sensitivity, enabling a truly "sample-in-answer-out" microsystem with exceptional performance., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: Upper cervical fracture combined with non-contiguous lower cervical fracture are not uncommon but complicated. In order to outline a management principle for the upper cervical fracture combined with non-contiguous lower cervical fracture and assess its clinical characteristics, we retrospectively analyzed 59 cases of patients who underwent surgical treatment for upper cervical fracture combined with non-contiguous lower cervical fracture., Methods: 59 patients of upper cervical fracture combined with non-contiguous lower cervical fracture were treated by surgery in our hospital. According to the AO Spine classification for cervical fractures, there were 21 cases of type B atlas fractures, nine cases of type C atlas fractures; 15 cases of type B axis fractures, 14 cases of type C axis fractures; 19 cases of type B lower cervical fractures, 40 cases of type C lower cervical fractures. The operation time, intraoperative blood loss, complications, VAS scores, JOA scores, ASIA grades, and radiological evaluation of cervical lordosis and stability were collected and recorded., Results: Our results showed the segments of upper cervical fracture combined with non-contiguous lower cervical fracture are mainly concentrated in the atlas-axis and C6, C7 levels. There were 43 cases (72.88%) of associated injuries, mainly involving head trauma and thoracic injuries. Four patients underwent anterior approach surgery only, 43 patients underwent posterior approach surgery only, and 12 patients underwent combined anterior and posterior approach surgery in one stage. All patients had regular follow up with an average duration of 67.83 ± 11.25 months (range, 39 to 103 months). The VAS scores and JOA scores at 12 months postoperatively and at final follow-up showed significant improvement compared to preoperative scores (P < 0.05). At the final follow-up, ASIA grades had improved by 0 to 2 levels. The cervical lordosis at the final follow-up (24.71°±7.39°) showed no statistically significant difference compared to preoperative measurements (26.89°±13.32°). Surgical complications occurred in 17 patients. No cases of vertebral artery injury, screw loosening, or other internal fixation failures were found at final follow-up., Conclusions: Upper cervical fracture combined with non-contiguous lower cervical fracture can result in varying extents of cervical spinal cord injury and combined trauma in other parts. Surgical treatment of these injuries can achieve favourable clinical and radiological outcomes in the medium to long term follow-up. More research is still needed to optimize clinical decision-making regarding surgical approach., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Camellia oleifera shell (COS) is a renewable biomass resource abundant in lignin with significant potential for producing phenolic monomers. However, the dearth of research has led to considerable resource wastage and environmental pollution. Herein, reductive catalytic fractionation (RCF) of COS was performed using noble metal catalysts in different solvents. An 11.1 wt% yield of phenolic monomers was achieved with 91% selectivity toward propylene-substituted monomers in H 2 O/EtOH (3:7, v/v) cosolvent under N 2 atmosphere. Notably, the highest phenolic monomer yield of 17.0 wt% was obtained with impressive selectivity (86.9%) toward propanol-substituted monomers in the presence of H 2 . The GPC analysis and 2D HSQC NMR spectra indicated the effective depolymerization of lignin oligomers with catalysts. Phenolic monomers with ethyl, propyl, or propanol side chain could be produced from lignin-derived oligomers through hydrogenolysis, hydrogenation, and decarboxylation reactions. Overall, this study has paved the way for the valorization of COS lignin through the RCF strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Postharvest fruits, especially climacteric fruits, are prone to ethylene ripening, browning and aging, microbial growth accelerated decay and other problems in natural environment. Herein, a carboxylated cellulose nanofibers/phytic acid‑titanium dioxide nanoparticles (CPT) biodegradable coating with "photocatalytic antibacterial barrier" structure，was developed by homogeneous dispersion of phytic acid(PA) complexed titanium dioxide nanoparticles (TNPs) in carboxylated cellulose nanofibers(CCNF). The CPT coating achieves effective dispersion and efficient utilization of TNPs through the complexation of PA. The coating ethylene clearance rate of CPT up to 70.89 %. Meanwhile, the coating exhibits excellent antibacterial (99.67 %), UV resistance, gas barrier. It was found that the CPT coating delays fruit ripening caused by ethylene, which effectively maintaining the quality of respiratory climacteric fruits and non- climacteric fruits, extending the shelf life of perishable fruit by up to 9 days. In particular, the coating is virtually biodegradable in soil after 21 days, which offers the possibility of replacing non-biodegradable multifunctional coatings in food packaging., Competing Interests: Declaration of competing interest There is no conflict of interest for any of the authors for this manuscript. We declare that we don't have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)