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Self-organization of mid-ocean ridge segments during oblique oceanisation
No full textAbstract Obliquely rifted continental margins are common, yet oblique spreading ridge segments are surprisingly rare. Oblique oceanisation, as seen in the southeast Indian Ocean, the Central Gulf of Aden, and the Equatorial Atlantic, invariably evolved into orthogonal ridge segments connected by transform faults. It remains unclear why the orthogonal ridge-transform configuration is preferred, and how it develops under sustained oblique divergence. Using 3D thermomechanical numeric models, we show that slow/ultraslow oblique spreading inherited from oblique rifting is a dynamic process. It enhances asymmetric oceanic plate growth with alternating directions and spontaneously self-organizes into orthogonal ridge segments connected with transform faults. The offset and spacing of the oceanic transform faults are controlled by the obliquity angle and the spreading rate. The step-wise orthogonal ridge-transform pattern is favored because it minimizes the total length of stronger ridge segments relative to weaker transforms, thereby reducing the mechanical work required for plate separation
Dislocation creep may control bridgmanite deformation in the Earth’s lower mantle
No full textAbstract Seismic anisotropy in the Earth’s lower mantle, particularly around subduction zones, is commonly attributed to deformation by dislocation creep, yet much of the lower mantle appears nearly isotropic. This contrast complicates interpretations of mantle rheology. Here we report the temperature dependence of lattice preferred orientation in bridgmanite, the most abundant lower mantle mineral, through high-pressure deformation experiments at 25 gigapascals and 1700–2100 kelvin. Both iron-free and iron-bearing bridgmanite develop lattice preferred orientations across this temperature range, with distinct slip systems occurring below and above 1800 kelvin. Low-temperature fabric produces strong seismic anisotropy, whereas high-temperature fabric yields weak, near-isotropic signatures under horizontal shearing. These results provide a unified explanation for strong seismic anisotropy near subduction zones and globally near-isotropic behavior of the lower mantle. They suggest that dislocation creep could dominate lower mantle deformation while generating diverse seismic signatures, providing important understanding for lower mantle rheology and dynamics
Enhanced language models for predicting and understanding HIV care disengagement: a case study in Tanzania
No full textAbstract Sustained engagement in HIV care and adherence to ART are crucial for meeting the UNAIDS “95-95-95” targets. Disengagement from care remains a significant issue, especially in sub-Saharan Africa. Traditional machine learning (ML) models have had moderate success in predicting disengagement, enabling early intervention. We developed an enhanced large language model (LLM) fine-tuned with electronic medical records (EMRs) to predict individuals at risk of disengaging from HIV care in Tanzania. Using 4.8 million EMR records from the National HIV Care and Treatment Program (2018–2023), we identified risks of ART non-adherence, non-suppressed viral load, and loss to follow-up. Our enhanced LLM may outperform traditional machine learning models and zero-shot LLMs. HIV physicians in Tanzania evaluated the model’s predictions and justifications, finding 65% alignment with expert assessments, and 92.3% of the aligned cases were considered clinically relevant. This model can support data-driven decisions and may improve patient outcomes and reduce HIV transmission
Towards a speech-based digital biomarker for cognitive impairment: speech as a proxy for cognitive assessment
No full textAbstract With the growing prevalence of cognitive decline in ageing populations, accessible and scalable screening tools are essential for early intervention. This study investigated the potential of automated speech analysis as a proxy for cognitive assessment in 1003 older adults. Employing machine learning regression models, we demonstrated that linguistic and acoustic features extracted from spontaneous speech quadrupled performance compared to models using demographic information alone, when predicting cognitive domain scores. We then trained a binary classifier to identify individuals performing below normative thresholds (ROC-AUC up to 0.81), illustrating possible applications such as large-scale screening for cognitive impairment and improved participant selection for clinical trials. Finally, we evaluated our approach on an independent clinical dataset of Alzheimer’s disease (AD) patients and controls, demonstrating its generalizability. These findings highlight the clinical feasibility of speech analysis as a low-cost, non-intrusive digital biomarker for cognitive monitoring and screening
Reply to determining MCID threshold for Knee Society Score to assess patient satisfaction in knee arthroplasty
No full textAbstract This reply addresses Wang et al.’s comments on our prior work and clarifies that the 34.5-point Knee Society Score threshold was derived from our previously validated, anchor-based approach. We agree that future research should refine predictive models by establishing consensus, standardised minimal clinically important difference cutoffs to enhance applicability and reliability in real-world clinical settings
Depression and anxiety in interstitial lung disease: a systematic review, meta-analysis and Mendelian randomization
No full textAbstract Objective To investigate the prevalence of depression and anxiety in interstitial lung disease (ILD) and reveal whether ILD is causally associated with depression and anxiety via Mendelian randomization (MR). Methods Eligible studies were identified and selected from Web of Science, PubMed and Scopus. The pooled prevalence of depression and anxiety in ILD, as well as the clinical characteristics of ILD with depression or anxiety, were assessed. Sensitivity analyses, subgroup analyses and meta-regression were applied for heterogeneity assessments. Data of MR analysis were derived from the UK biobank and Finngen cohort, and the inverse variance weighting approach was selected as the main approach for causality evaluation. Results A total of 35 studies were included in this meta-analysis, with 34 studies reporting depression in ILD and 21 reporting anxiety in ILD. The pooled prevalence of depression and anxiety in ILD were 22% (95% CI 17%, 26%, I2 = 97%) and 25% (95% CI 18%, 32%, I2 = 98%), respectively. There was no significant difference in the prevalence of depression (p = 0.41) or anxiety (p = 0.39) across various subtypes of ILD. ILD patients with depression had a lower BMI (MD −2.11, 95% CI −3.82, −0.41, p = 0.02). Results of MR analysis revealed no causal associations for either the ILD-depression (OR 1.000, 95% CI 0.997, 1.003; p = 0.962) or the ILD-anxiety (OR 1.000, 95% CI 0.998, 1.002; p = 0.888) relationships. Conclusion Although the prevalence of depression and anxiety were high in patients with ILD, no causal relationship was observed. Future studies are needed to investigate the intricate association between ILD and mental health
Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice
No full textAbstract This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticle pretreatment to inhibit lipopolysaccharide (LPS)-induced pathological inflammation, synapse destruction, and depressive and anxiety behavior in mice. B6SJLF1/J adult mice were pretreated with intranasal dantrolene nanoparticles (dantrolene: 5 mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Afterwards, mice were treated with a single intraperitoneal injection of LPS (5 mg/kg). Behavioral tests for depression and anxiety were performed 24 h after the one-time LPS injection. Biomarkers for pyroptosis-related inflammation cytokine levels (IL-1β and IL-18) in the blood and brain were measured using enzyme-linked immunosorbent assay (ELISA) and immunoblotting, respectively. Changes in primary protein (NLRP3: NLR family pyrin domain containing 3, Caspase-1, N-GSDMD: N-terminal protein gasdermin D) and synapse protein-related (PSD-95 and synaptin-1) activation of inflammatory pyroptosis in mouse brains were measured using immunoblotting. Results indicated that intranasal dantrolene nanoparticle treatment robustly inhibited LPS-induced increases in depressive and anxiety behavior, LPS-induced pathological elevation of IL-1β and IL-18 levels in the blood and brain, and LPS-induced activation of pyroptosis. Furthermore, intranasal dantrolene nanoparticles significantly inhibited decreased PSD-95 and synaptin-1 levels. Intranasal dantrolene nanoparticles have demonstrated neuroprotective effects against inflammation-mediated depression and anxiety behaviors and should be studied further as a future effective drug treatment of major depressive or anxiety disorders
Interferon-α enhances NK cell function to counteract autologous platelet-mediated tumor immune evasion
No full textAbstract Background Natural Killer (NK) cells, a cellular defense component of the innate immune system, play a vital role in anti-tumor immunity. As interest in NK cell-based therapies grows within the field of cancer treatment, assessing potential negative interferences and adverse interactions is essential. Although platelets are recognized as modulators of tumor immunity, the impact of autologous platelets on NK cell function remains insufficiently explored in the realm of personalized medicine. Methods To investigate the role of autologous platelets in modulating NK cell activity, we developed a novel assessment platform using fresh blood samples from 34 healthy donors (25 females, 9 males; mean age 28.29 ± 6.25 years). NK cells, with or without prior IFN-α stimulation, were co-cultured with K562 leukemia cells in the presence or absence of autologous platelets to assess functional responses. Results NK cells can exert anti-tumor immunity by releasing cytokines like IFN-γ and directly eliminating tumor cells through cytotoxic granules. In our co-culture system, platelets demonstrated suppressive effects on NK cell IFN-γ production and cytotoxic degranulation, resulting in impaired tumor cell killing. Notably, this suppression was effectively reversed by IFN-α treatment, which restored NK cell cytotoxic function and cytokine responses in all donors tested. Conclusion Our study reveals that autologous platelets compromise NK cell-mediated anti-tumor responses, but this suppression can be overcome with IFN-α treatment. The assessment platform we introduced provides a practical tool to study platelet–NK–tumor interactions and serves as a valuable model for screening immunomodulatory agents and tailoring NK cell-based therapies
TGFBI deficiency facilitates tumor associated macrophages M2 polarization and angiogenesis to promote pancreatic neuroendocrine neoplasms progression
No full textAbstract Background Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) that influence tumor progression through immunomodulation, angiogenesis, and extracellular matrix remodeling. Transforming growth factor-beta-induced protein (TGFBI) has demonstrated context-dependent roles in cancer; however, its function in pancreatic neuroendocrine neoplasms (pNENs) remains unclear. This study investigates the role of TGFBI in the progression of pNENs and its interaction with TAMs. Methods We employed lentiviral-mediated knockdown and overexpression systems to modulate TGFBI levels in pNEN cell lines (QGP-1, BON-1) and macrophage-like THP-1 cells. Functional assays, including CCK-8, EdU, transwell migration, and tube formation assays, were conducted to evaluate tumor proliferation, invasion, and angiogenesis. Tumor xenograft models were established to assess in vivo effects. Transcriptomic analyses, including RNA sequencing, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed to explore the underlying molecular mechanisms. Results TGFBI is silenced in pNENs and associated with TAM M2 macrophage. Down-regulation of TGFBI in pNEN cells promoted proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Silencing TGFBI enhanced M2 macrophage polarization, as evidenced by increased CD206 expression and activation of the JAK2/STAT3 pathway. Additionally, TGFBI deficiency facilitated angiogenesis both in vitro and in vivo, accompanied by elevated VEGFA expression. Over-expression of TGFBI or treatment with recombinant protein reversed these pro-tumorigenic effects. Conclusions TGFBI functions as a tumor suppressor in pNENs by modulating TAM polarization, angiogenesis, and tumor cell behavior, largely through the JAK2/STAT3 signaling pathway. These findings reveal a novel role for TGFBI in the TME of pNENs and suggest its potential as a biomarker and therapeutic target. Graphical Abstrac
Collection and reporting of waste data to support waste management policies
No full textAbstract Policies for waste management, including target setting, infrastructure planning and circular economy interventions, crucially depend on the availability and quality of waste data. This paper evaluates the Waste Data Interrogator for England (WDI), a key database compiling reports from permitted waste facilities managing controlled wastes and compares it with six other European databases. Its usefulness for policy-making was evaluated across five key aspects: classification effectiveness, information comprehensiveness, suitability for spatial analytics, clarity and user-friendliness and reliability. The analysis focused on construction, demolition and excavation waste, which is the largest waste stream in the database and in many regions globally, and a common policy priority. Our analysis of the WDI in a European context provides internationally relevant insights and identifies areas for improvement. Recommendations include refining classification to inform recovery, broadening statistical coverage, strengthening spatial detail, enhancing metadata and promoting digitalisation, all of which support better evidence-based waste management policy-making
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