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Scale-up upcycling of waste polyethylene terephthalate plastics to biodegradable polyglycolic acid plastics
Analysis of sleep disorders and their influencing factors in patients with ankylosing spondylitis
Objectives Sleep disorders are a common symptom in Ankylosing Spondylitis (AS) patients. In this cross-sectional study, we aimed to understand the current status of sleep disorders in AS patients and to analyze potential factors influencing sleep disorders. Methods A total of 205 AS patients were recruited in the survey. The content included the self-designed demographic data questionnaire, The MOS 36-Item Short Form Health Survey (SF-36), Visual Analogue Scale (VAS), Multidimensional Fatigue Inventory (MF-20), Self-Rating Anxiety and Depression Scale, Pittsburgh Sleep Quality Index questionnaire (PSQI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI). These data were analyzed using chi-square test, independent sample t-test, Mann-Whitney U test, Pearson correlation analysis, single-factor linear regression analysis, and multiple linear stepwise regression analysis. Results The results showed that the average sleep total score was 8.82 ± 4.146, and the prevalence of sleep disorders was approximately 66.8% in AS patients. Age (F = 29.710, P < 0.001), disease duration (F = 13.025, P < 0.001), anxiety (F = 36.060, P < 0.001), depression (F = 11.808, P < 0.001), and quality of life (t = 6.665, P < 0.001) significantly impacted the sleep total score. Pearson correlation analysis revealed a significant negative correlation between SF-36 total score and sleep total score (r = ‒0.449, P < 0.01), while positive correlations were observed for VAS score, fatigue, anxiety, depression, BASDAI, BASFI, BASMI, age, and disease duration (all P < 0.01). Multivariate analysis showed that age, disease duration, nocturnal pain VAS score, total back pain VAS score, peripheral joint pain VAS score, total fatigue score, total anxiety score, and BASMI total score significantly predicted sleep total score (R² = 0.755, F = 45.334, P < 0.001). Conclusion These findings suggest that medical professionals should pay increased attention to the observed associations between sleep disorders and clinical factors in AS patients, and consider implementing targeted interventions to address sleep-related issues.
Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs
Abstract Hypomethylating agents are frontline therapies for myelodysplastic neoplasms (MDS), yet clinical responses remain unpredictable. We conducted a phase 2 trial comparing injectable and oral azacitidine (AZA) administered over one or three weeks per four-week cycle, with the primary objective of investigating whether response is linked to in vivo drug incorporation or DNA hypomethylation. Our findings show that injection results in higher drug incorporation, but lower DNA demethylation per cycle, while global DNA methylation levels in mononuclear cells are comparable between responders and non-responders. However, hematopoietic stem and progenitor cells (HSPCs) from responders exhibit distinct baseline and early treatment-induced CpG methylation changes at regulatory regions linked to tissue patterning, cell migration, and myeloid differentiation. By cycle six—when clinical responses typically emerge—further differential hypomethylation in responder HSPCs suggests marrow adaptation as a driver of improved hematopoiesis. These findings indicate that intrinsic baseline and early drug-induced epigenetic differences in HSPCs may underlie the variable clinical response to AZA in MDS.
Correction: Exploring the needs of stroke patients after discharge from rehabilitation centres in Saudi Arabian communities: An IPA qualitative exploratory study design
The immune NIK1/RPL10/LIMYB signaling module regulates photosynthesis and translation under biotic and abiotic stresses.
Multidimensional correlates of psychological stress: Insights from traditional statistical approaches and machine learning using a nationally representative Canadian sample
Approximately one-fifth of Canadians report high levels of psychological stress. This is alarming, as chronic stress is associated with non-communicable diseases and premature mortality. In order to create effective interventions and public policy for stress reduction, factors associated with stress must be identified and understood. We analyzed data from the 2012 ‘Canadian Community Health Survey - Mental Health’ (CCHS-MH), including 66 potential correlates, drawn from a range of domains (e.g., psychological, physical, social, demographic factors). First, we used a random forest algorithm to determine the most important predictors of psychological stress, then we used linear regressions to quantify the linear associations between the important predictors and psychological stress. In total, 23,089 Canadian adults responded to the 2012 CCHS-MH, which was weighted to be nationally representative. Random forest analyses found that, after accounting for variance from other factors and considering complex interactions, life satisfaction (relative importance = 1.00), negative social interactions (0.99), primary stress source (0.85), and age (0.77) were the most important correlates of psychological stress. To a lesser extent, employment status (0.36), was also an important variable. Univariable linear regression suggested that these variables had effects ranging from small to medium-to-large. Multiple linear regression showed that lower life satisfaction, being younger, greater negative social interaction, reporting a primary stressor, and being employed were all found to be associated with greater psychological stress (beta range = 0.03 to 0.84, all p < 0.001, R2 = 0.264). Further, these factors accounted for 26% of the variance of psychological stress. This study highlights that the most important correlates of stress reflect diverse psychological, social, and demographic factors. These findings highlight that stress reduction interventions may require a multidisciplinary approach. However, further longitudinal and experimental studies are required.
Inorganic-organic hybrid metamaterials with switchable high stiffness and elasticity
Soft, skin-interfaced wireless electrogoniometry systems for continuous monitoring of finger and wrist joints
Multicenter target trial emulation to evaluate corticosteroids for sepsis stratified by predicted organ dysfunction trajectory
Diminished biophysical cooling benefits of global forestation under rising atmospheric CO2
Low temperature near-field fingerprint spectroscopy of 2D electron systems in oxide heterostructures and beyond
Abstract Confined electron systems, such as 2D electron gases (2DEGs), 2D materials, or topological insulators, show great technological promise but their susceptibility to defects often results in nanoscale inhomogeneities with unclear origins. Scattering-type scanning near-field optical microscopy (s-SNOM) is useful to investigate buried confined electron systems non-destructively with nanoscale resolution, however, a clear separation of carrier concentration and mobility was so far impossible in s-SNOM. Here, we predict a previously inaccessible characteristic “fingerprint” response of the prototypical LaAlO3/SrTiO3 2DEG, and verify it using a state-of-the-art tunable narrow-band laser in mid-infrared cryo-s-SNOM at 8 K. Our modeling allows us to separate the influence of carrier concentration and mobility on fingerprint spectra and to characterize 2DEG inhomogeneities on the nanoscale. Finally, we model the surface accumulation layer in doped InAs, to show that our fingerprint spectra are a universal feature and generally applicable to confined electron systems, like topological insulators or stacked van-der-Waals materials.
Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial
Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.
Vitamin D supplementation ameliorates ductular reaction, liver inflammation and fibrosis in mice by upregulating TXNIP in ductular cells
Combining spatial transcriptomics with tissue morphology
Sex differences in the genetic regulation of the human plasma proteome
Abstract Mechanisms underlying sex differences in the development and prognosis of many diseases remain largely elusive. Here, we systematically investigated sex differences in the genetic regulation of plasma proteome (>5800 protein targets) across two cohorts (30,307 females; 26,058 males). Plasma levels of two-thirds of protein targets differ significantly by sex. In contrast, genetic effects on protein targets are remarkably similar across sexes, with only 103 sex-differential protein quantitative loci (sd-pQTLs; for 2.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). A third of those show evidence of sexual discordance, i.e., effects observed in one sex only (n = 30) or opposite effect directions (n = 1 for CDH15). Phenome-wide analyses of 365 outcomes in UK Biobank did not provide evidence that the identified sd-pQTLs accounted for sex-differential disease risk. Our results demonstrate similarities in the genetic regulation of protein levels by sex with important implications for genetically-guided drug target discovery and validation.
A clinically applicable AI system for detection and diagnosis of bone metastases using CT scans
GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates
Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
Tad pili with adaptable tips mediate contact-dependent killing during bacterial predation
Abstract The predatory bacterium, Myxococcus xanthus, kills its prey by contact, using a putative Tight Adherence pilus, known as the Kil system, along with a protein complex resembling the basal body a type-III secretion system, named the “needleless” T3SS*. In this work, we provide direct evidence that Myxococcus polymerizes a Kil pilus at the prey contact site, which is constituted by the major pilin KilP. We also genetically demonstrate that the predation function of this pilus is linked to four different minor pilin complexes, which work in specific combinations to detect and kill phylogenetically diverse bacterial species. Structural models of the Kil pilus suggest that these minor pilin complexes form interchangeable “Tips”, exposing variable domains at the extremity of the pilus to interact with prey cells. Remarkably, the activity of these Tips also depends on the T3SS*, revealing a tight functional connection between the Kil system and the T3SS*. While these Tips are mostly restricted to predatory bacteria, genomic and structural analyses suggest that in other bacteria, including pathogens, Tad pili are also customized and functionalized by similar minor pilin complexes exposing variable domains.