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In this short report, we show that some elements usually deemed as obligatory DE SE anaphors may be interpreted as NON-DE SE in certain contexts. We argue that this non-de se reading cannot be subsumed under the category of DE RE, and suggest extending Kuno and Kaburaki's Theory of Empathy (Kuno & Kaburaki 1977, Kuno 1987) to interpret these readings as Indirect De Se: namely, that the speaker empathizes with the attitude holder, helping the latter to do self-reference. Applying this idea to other anaphoric expressions like personal pronouns, we obtain a TRICHOTOMY of attitude reports—de se, de re, and indirect de se, contra the traditional de se and de re distinction. Our proposal can also help to account for Anand's (2006) observation that only firstperson attitude reports in the Past Tense may have the non-de se reading.
While various delivery formats of cognitive–behavioural therapy (CBT) for obsessive–compulsive disorder (OCD) are available, comprehensive evidence on their comparative effectiveness and acceptability is lacking.
Aim
To examine the comparative effectiveness and acceptability of different CBT delivery formats for OCD.
Method
An existing database of psychological interventions for OCD was utilised, with randomised controlled trials (RCTs) comparing CBT delivery formats with each other/control groups were included. Pairwise and network meta-analyses were conducted using a random-effects model. Comparative standard mean differences (SMDs) were calculated for effectiveness in reducing OCD symptom severity post-treatment. Relative risks were calculated for acceptability (conceptualised as any cause discontinuation in the acute treatment phase).
Results
A total of 61 RCTs involving 3710 patients with OCD were included. All CBT treatment formats were significantly more effective than control groups (SMDs: −0.39 to −1.66). No significant differences were found among individual, remote-delivery, guided self-help, time-intensive and family-involved formats. However, individual, remote-delivery and family-involved formats were more effective than group (SMDs, −0.38 to −0.60), and most treatment formats were more effective than unguided self-help (SMDs, −0.58 to −0.80). Regarding acceptability, most CBT formats showed no significant differences among themselves, although they were generally more acceptable (relative risks: 1.11–1.18) than unguided self-help.
Conclusions
Most CBT delivery formats serve as potential alternatives to conventional individual CBT. Unguided self-help has lower but still moderate effects in reducing OCD symptom severity, and it holds important potential for assisting a larger number of individuals with OCD who face barriers to accessing treatments.
Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.
Methods
A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.
Results
Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.
Conclusions
Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.
Antimicrobial resistance (AMR) is a global health challenge, highlighting the need for antibiotic stewardship policies. We evaluated the impact of the National Action Plan to Contain Antimicrobial Resistance (2022–2025) on antibiotic use among primary healthcare institutions (PHIs) in Central China.
Design:
A segmented interrupted time-series analysis from January 2021 to December 2023.
Methods:
We collected data from 1510 PHIs, by region, types of healthcare institutions and medication type, assessing antibiotic consumption using defined daily doses per 1000 inhabitants per day and the quality by the percentage of broad-spectrum antibiotics.
Results:
Post-intervention, antibiotic consumption declined by −35.96% (95%CI: –49.34 to –22.57), and the proportion of broad-spectrum antibiotic use decreased by –41.97% (–61.74 to –22.20). Consumption dropped significantly in both moderately developed areas and underdeveloped areas, while highly developed areas saw the largest reduction in broad-spectrum antibiotic use. Rural PHIs also showed notable declines in both overall antibiotic consumption and broad-spectrum usage.
Conclusions:
The policy was associated with a reduction in antibiotic use across PHIs, though regional disparities in its implementation suggest uneven benefits.
This meta-analysis assesses the relationship between vitamin D supplementation and incidence of major adverse cardiovascular events (MACE). PubMed, Web of science, Ovid, Cochrane Library and Clinical Trials were used to systematically search from their inception until July 2024. Hazard ratios (HR) and 95 % CI were employed to assess the association between vitamin D supplementation and MACE. This analysis included five randomised controlled trials (RCT). Pooled results showed no significant difference in the incidence of MACE (HR: 0·96; P = 0·77) and expanded MACE (HR: 0·96; P = 0·77) between the vitamin D intervention group and the control group. Further, the vitamin D intervention group had a lower incidence of myocardial infarction (MI), but the difference was not statistically significant (HR: 0·88, 95 % CI: 0·77, 1·01; P = 0·061); nevertheless, vitamin D supplementation had no effect on the reduced incidence of stroke (P = 0·675) or cardiovascular death (P = 0·422). Among males (P = 0·109) and females (P = 0·468), vitamin D supplementation had no effect on the reduced incidence of MACE. For participants with a BMI < 25 kg/m2, the difference was not statistically significant (P = 0·782); notably, the vitamin D intervention group had a lower incidence of MACE for those with BMI ≥ 25 kg/m2 (HR: 0·91, 95 % CI: 0·83, 1·00; P = 0·055). Vitamin D supplementation did not significantly contribute to the risk reduction of MACE, stroke and cardiovascular death in the general population, but may be helpful for MI. Notably, the effect of vitamin D supplementation for MACE was influenced by BMI. Overweight/obese people should be advised to take vitamin D to reduce the incidence of MACE.
Clinical high risk for psychosis (CHR) is often managed with antipsychotic medications, but their effects on neurocognitive performance and clinical outcomes remain insufficiently explored. This study investigates the association between aripiprazole and olanzapine use and cognitive and clinical outcomes in CHR individuals, compared to those receiving no antipsychotic treatment.
Methods
A retrospective analysis was conducted on 127 participants from the Shanghai At Risk for Psychosis (SHARP) cohort, categorized into three groups: aripiprazole, olanzapine, and no antipsychotic treatment. Neurocognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were assessed through the Structured Interview for Prodromal Syndromes (SIPS) at baseline, 8 weeks, and one year.
Results
The non-medicated group demonstrated greater improvements in cognitive performance, clinical symptoms, and functional outcomes compared to the medicated groups. Among the antipsychotic groups, aripiprazole was associated with better visual learning outcomes than olanzapine. Improvements in neurocognition correlated significantly with clinical symptom relief and overall functional gains at follow-up assessments.
Conclusions
These findings suggest potential associations between antipsychotic use and cognitive outcomes in CHR populations while recognizing that observed differences may reflect baseline illness severity rather than medication effects alone. Aripiprazole may offer specific advantages over olanzapine, underscoring the importance of individualized risk-benefit evaluations in treatment planning. Randomized controlled trials are needed to establish causality.
The previous study indicated that ubiquitination is involved in the freezing tolerance of hydrated seeds. Parthenolide (PN), inducing the ubiquitination of MDM2, an E3 ring-finger ubiquitin ligase, adversely affects the freezing tolerance of hydrated lettuce seeds. Therefore, a proteomics analysis was conducted to identify PN's targets in hydrated seeds exposed to cooling conditions. Several pathways, including oxidative phosphorylation (KEGG00190), amino sugar and nucleotide sugar metabolism (KEGG00520), and biosynthesis of nucleotide sugars (KEGG01250), were enriched in the PN treatment under slow-cooling conditions (3°C h−1, P < 0.05). Among the proteins in oxidative phosphorylation, the expression of NADH dehydrogenases and ATP synthases (ATPsyn) decreased in PN treatment. In contrast, uncoupling proteins increased after PN treatment, which led to the dissociation of the electron transport chain from ATP synthesis. Treatments with rotenone, dicoumarol, and oligomycin (i.e., oxidative phosphorylation inhibitors) decreased the survival rate of hydrated seeds under freezing conditions, which indicated that energy metabolism was related to the freezing tolerance of hydrated seeds. The predicted interactions between PN and MDM2-like proteins of Lactuca indicated that LsMDM2-5 forms two potential hydrogen bonds with PN. Furthermore, based on AlphaFold predictions and yeast 2-hybrid results, MDM2-5 might interact directly with NADH2. The knockdown of MDM2-5 by RNAi caused a higher level of NADH2 and ATPsyn and a higher freezing tolerance of hydrated seeds. This indicated that MDM2 played negative roles in regulating ATP synthesis and freezing tolerance of hydrated seeds.
A high-fat diet (HFD) increases susceptibility to Escherichia coli colonization in the intestine and raises the risk of intestinal diseases. Lactobacillus reuteri, a commensal bacterium, plays a crucial role in regulating intestinal function and maintaining immune homeostasis. In this study, we aimed to evaluate the effects of L. reuteri on gut barrier function and systemic inflammation in HFD-fed mice challenged with Shiga toxin-producing E. coli O157:H7, and to further elucidate the potential protective mechanisms involved. The results show that supplementation of L. reuteri ZJ617 mitigates intestinal barrier impairment, inflammatory cell infiltration and systemic inflammation induced by E. coli O157:H7. The potential mechanisms of L. reuteri ZJ617 deal with it involving in forming biofilm, producing functional amino acids and various secondary metabolites. Our works provided comprehensively analysis of potential properties of L. reuteri ZJ617 and indicated that L. reuteri ZJ617 is a promising probiotic to prevent E. coli O157:H7 infection.
The flexible delivery of single-frequency lasers is far more challenging than that of conventional lasers due to the onset of stimulated Brillouin scattering (SBS). Here we present the successful delivery of 100 W single-frequency laser power through 100 m of anti-resonant hollow-core fiber (AR-HCF) in an all-fiber configuration, with the absence of SBS. By employing a custom-designed AR-HCF with a mode-field diameter matching that of a large-mode-area panda fiber, the system achieves high coupling efficiency without the need for free-space components or fiber post-processing. The AR-HCF attains a transmission efficiency of 92%, delivering an output power of 100.3 W with a beam quality factor (M2) of 1.22. The absence of SBS is confirmed through monitoring backward light, which shows no increase in intensity. This all-fiber architecture ensures high stability, compactness and efficiency, potentially expanding the application scope of single-frequency lasers in high-precision metrology, optical communication, light detection and ranging systems, gravitational wave detection and other advanced applications.
With increased global navigation satellite system (GNSS) signals and degraded observation environments, the correctness of ambiguity resolution is disturbed, causing unexpected real-time kinematic (RTK) positioning solutions. This paper presents an improved fault detection and exclusion (FDE) method based on the generalized least squares (GLS) model. The correlated GLS model is constructed by regarding double-differencing (DD) integer ambiguities as the known parameters. Meanwhile, the validity of residuals as crucial components of fault detection could be enhanced by the iterative re-weighted least squares (IRLS) method rather than the least squares (LS) without robustness. A static test with artificial faults and a dynamic test with natural faults were carried out, respectively. By analyzing test statistics of the enhanced FDE algorithm and comparing its positioning errors with those from the classical LS, it is shown that our method can provide high-precision and high-reliability RTK solutions facing wrong DD fixed ambiguities due to observation faults.
A conceptual framework, called Innovation of Health Technology Assessment Methods (IHTAM), has been developed to facilitate the understanding of how to innovate methods of health technology assessment (HTA). However, the framework applicability has not been evaluated in practice. Hence, we aimed to explore framework applicability in three cases of method innovation that are part of the HTx project and to develop a roadmap to improve framework applicability.
Methods
The IHTAM framework was applied to three cases of innovating HTA methods. We collected feedback from case study leaders and consortium members after a training session, an approximately 1-year follow-up of periodic case study meetings, and a general assembly meeting where innovation progresses of the three cases were reported through surveys and interviews. Feedback was then summarized using an open-coding technique.
Results
According to feedback, the framework provided a structured way of deliberation and helped to improve collaboration among HTA stakeholders. However, framework applicability could be improved if it was complemented by a roadmap with a loop structure to provide tailored guidance for different cases, and with items to elaborate actions to be taken by stakeholders. Accordingly, a 48-item roadmap was developed.
Conclusions
The IHTAM framework was generally applicable to the three case studies. A roadmap, with loop structure and actionable items, could complement the framework, and may provide HTA stakeholders with tailored guidance on developing new methods. To further examine the framework applicability, we recommend stakeholders to apply the IHTAM framework and its roadmap in future practice.
The sandbox approach, developed in the financial technologies sector, creates an environment to collaboratively develop and test innovative new products, methods and regulatory approaches, separated from business as usual. It has been used in health care to encourage innovation in response to emerging challenges, but, until recently, has not been used in health technology assessment (HTA). This article summarizes our learnings from using the sandbox approach to address three challenges facing HTA organizations and to identify implications for the use of this approach in HTA.
Methods
We identified three challenging contemporary HTA-related topics to explore in a sandbox environment, away from the pressures and interests of “live” assessments. We convened a pool of 120 stakeholders and experts to participate in various sandbox activities and ultimately co-develop solutions to help HTA organizations respond to the identified challenges.
Results
Important general learnings about the potential benefits and implementation of a sandbox approach in HTA were identified. Consequently, we developed recommendations to guide its use, including how to implement an HTA sandbox in an effective way and the types of challenges for which it may be best suited.
Conclusions
For many HTA organizations, it is difficult to carefully consider emerging challenges and innovate their processes due to risks associated with decision errors and resource limitations. The sandbox approach could reduce these barriers. The potential benefits of addressing HTA challenges in a collaborative “safe space” are considerable.
This study presents observations of coherent modes (CMs) in a spherical tokamak using a microwave interferometer near the midplane. The CMs within the 30–60 kHz frequency range were observed during electron cyclotron resonance heating only, and the frequency of the CMs increased proportionally with the square root of the electron temperature near $R = 0.7m$. Generally, these modes displayed bursting and chirping signatures with strong density rise and fall. Their appearance indicated an increase in the intensity of hard x rays, suggesting a deterioration in energetic electron confinement. Furthermore, the effect of CMs on the intensity of energetic electron-driven whistler waves was observed. They decreased when CMs were present and gradually increased with the decrease in CM intensity. The CMs may influence the intensity of whistler waves by affecting the energetic electron confinement.
Certain rhythmic arterial pressure waves in humans and animals have been noticed for over one century. We found the novel and slowest arterial pressure waves in children following surgical repair for CHD, and examined their characteristics and clinical implications.
Methods:
We enrolled 212 children with 22 types of CHD within postoperative 48 h. We monitored haemodynamics (blood pressure, cardiac cycle efficiency, dP/dTmax), cerebral (ScO2), and renal (SrO2) oxygen saturation every 6 s. Electroencephalogram was continuously monitored. Mean blood flow velocity (Vm) of the middle cerebral artery was measured at 24 h.
Results:
We found the waves with a frequency of ∼ 90 s immediately following surgical repair in 46 patients in 12 types of CHD (21.7%), being most prevalent in patients with aortic arch abnormalities (Aorta Group, n = 24, 42.3%) or ventricular septal defect (Ventricular Septal Defect Group, n = 12, 23.5%). In Aorta and Ventricular Septal Defect Groups, the occurrence of the waves was associated with lower blood pressures, dP/dTmax, cardiac cycle efficiency, ScO2, SrO2, Vm, worse electroencephalogram background abnormalities, higher number of electroencephalogram sharp waves, and serum lactate (Ps <0.0001–0.07), and were accompanied with fluctuations of ScO2 and SrO2 in 80.6% and 69.6% of patients, respectively.
Conclusions:
The waves observed in children following cardiovascular surgery are the slowest ever reported, occurring most frequently in patients with aortic arch abnormalities or ventricular septal defect. While the occurrence of the waves was associated with statistically worse and fluctuated ScO2 and SrO2, worse systemic haemodynamics, and electroencephalogram abnormalities, at present these waves have no known clinical relevance.
This study investigated the impact of diallyl disulfide (DADS) on oxidative stress induced by hydrogen peroxide (H2O2) in ovine rumen epithelial cells (RECs). Initially, the effects of DADS were evaluated on cellular reactive oxygen species (ROS) levels, antioxidant capacity in RECs were estimated. Then, RNA-seq analysis was conducted in DADS-treated and untreated cells to analyze the differential gene expression, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, the effects of DADS on Kelch-like ECH associated protein 1/the nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) signaling pathway in RECs were evaluated. Results showed that DADS remarkably enhanced superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) (P < 0.05) while reducing ROS and malonaldehyde production (P < 0.05) in H2O2-treated RECs. Transcriptomic analysis revealed that DADS might influence glutathione synthesis through cysteine and methionine metabolism, thereby affecting the transcription of genes involved in immunity and oxidative stress. The DADS treatment resulted in increased nuclear translocation of Nrf2 and upregulation of mRNA and protein levels of quinone oxidoreductase 1, heme oxygenase 1, and Nrf2. The Nrf2-specific inhibitor nullified the protective effects of DADS on malonaldehyde formation induced by H2O2 and decreased T-AOC and SOD activities. In conclusion, DADS demonstrated the ability to alleviate oxidative stress in RECs by promoting antioxidative capacity through the Keap1/Nrf2 signaling pathway.
Although numerous studies have examined the effects of psychological treatments for obsessive-compulsive disorder (OCD), their overall effectiveness remains unclear. We aimed to estimate their overall effect by combining all available randomized controlled trials (RCTs) comparing psychological treatments to control groups for OCD.
Methods
We conducted a meta-analysis of 48 RCTs with 55 comparisons published between 1992 and 1 January 2023. The primary outcome was OCD symptom severity, with Hedges' g calculated at post-treatment and follow-up. Random-effects models were employed for all analyses, and the risk of bias was assessed.
Results
In general, psychological treatments demonstrated a significantly large effect (g = −1.14; 95% CI [−1.31 to −0.97]; I2 = 72.23%) on reducing OCD symptom severity post-treatment, this finding remained consistent across measures and after excluding outliers, but lost significance in the sensitivity analysis for only studies with low risk of bias. Type of treatment, control group and treatment format were associated with treatment effects. Moreover, more severe baseline OCD symptom severity predicted higher degree of treatment efficacy. No significant differences were observed in dropout rates between the treatment and control groups. Treatment effects lost significance at 3–6 and 6–12 month follow-ups. 87% of RCTs were rated at high risk of bias.
Conclusions
Psychological treatments are effective in reducing OCD symptom severity. However, caution should be exercised when interpreting these results due to the high heterogeneity and risk of bias across RCTs. Future studies with more rigorous methodology are required, as well as studies examining their long-term effectiveness.
Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver’s operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65–0·75) v. 0·63 (0·58–0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.
Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations.
Methods
A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed.
Results
Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively.
Conclusions
The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.
The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about under the reasonable assumption of constant mass density.