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Psychometric properties of the Adult Primary Care Assessment Tool Short form (PCAT-S) among high-risk patients in Australian general practice
Introduction The Primary Care Assessment Tool (PCAT) is designed to assess a patient’s experience with primary care across various core and ancillary domains, including First contact – Utilization, First contact – Access, Ongoing Care, Coordination, Comprehensiveness (services provided), Family-centeredness, Community Orientation, and Cultural Competence. This study examined the psychometric properties of the Adult Primary Care Assessment Tool Short Form (PCAT-S) in the Australian general practice setting. Method Data included 715 participants from the EQuIP-GP study, a cluster randomized controlled trial (RCT) conducted with adults aged 18–65 years with a chronic illness or aged over 65 years, from 34 general practices across Australia. For each subscale we assessed internal consistency using Cronbach’s alpha. Factor structure of the PCAT-S instrument was assessed through confirmatory and exploratory factor analysis, using three samples with different methods for handling ‘don’t know/can’t remember’ responses. Results The findings were mixed. Specifically, the subscales related to First Contact – Utilization, Ongoing Care and Comprehensiveness, demonstrated satisfactory internal consistency. However, the remaining subscales showed weak internal consistency. Confirmatory factor analysis indicated potential model misspecification, while exploratory factor analysis generally supported the hypothesized factor structure, albeit with some observed deviations. Conclusions The findings indicate the PCAT-S shows promise as an instrument to evaluate primary care experiences in Australia. However, the observed variability in internal consistency, along with issues identified in confirmatory and exploratory factor analyses, highlight the need for further validation and refinement in this population. Further research is required to address the identified limitations and enhance the tool’s applicability within the Australian general practice context.
Morphological, biochemical, and SSR molecular insights of jamun (Syzygium cumini Skeels)
MLND-IU: A multi-stage detection model of subcentimeter lung nodule with improved U-Net++
To address the challenges of high miss rates in subcentimeter nodules, false positives caused by vascular adhesion, and insufficient multi-scale feature fusion in lung CT analysis, a multi-stage detection model named MLND-IU, which incorporates an improved U-Net++ architecture, is proposed. The three-stage framework begins with an enhanced RetinaNet optimized by a dynamic focal loss to generate candidate regions with high sensitivity while mitigating class imbalance. The second stage introduces AG-UNet++ with a novel Dense Attention Bridging Module (DABM), which employs a tensor product fusion of channel and deformable spatial attention across densely connected skip pathways to amplify feature representation for 3–5 mm nodules. The final stage employs a 3D Contextual Pyramid Module (3D-CPM) to integrate multi-slice morphological and contextual features, thereby reducing vascular false positives. Ablation studies indicated that the second stage improved the Dice coefficient by 21.1% compared with the first stage (paired t-test, p < 0.01, independent validation on LIDC-IDRI). The third stage further reduced the false positives per scan (FP/Scan) to 1.4, corresponding to an 87.3% reduction compared to the baseline. Multicenter validation on the LIDC-IDRI (n = 1,018) and DSB2017 (n = 1,595) datasets resulted in a segmentation Dice coefficient of 92.7%, a sensitivity of 93.4% for nodules smaller than 6 mm (compared to radiologists’ sensitivity of 68.5%, p = 0.003), and an AUC of 0.84 for malignancy classification, representing a 19.2% improvement over conventional methods. With a processing time of 2.3 seconds per case, the proposed framework presents a clinically viable solution for early lung cancer screening by simultaneously improving small nodule detection and suppressing false positives.
Epidemiological characteristics of Mycoplasma pneumoniae in hospitalized children before during and after the COVID-19 pandemic in xi’an China
Abstract Background Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children. The COVID-19 pandemic and associated public health interventions have significantly influenced the epidemiology of respiratory infections. This single-center retrospective cohort study aimed to evaluate changes in MP infection patterns among children before, during, and after the COVID-19 pandemic. Methods We analyzed data from 15,718 pediatric patients (aged 1–18 years) with CAP admitted to Shaanxi Provincial People’s Hospital between January 2017 and December 2023. The study periods were defined as pre-pandemic (January 1, 2017, to January 22, 2020), pandemic (January 23, 2020, to December 11, 2022), and post-pandemic (December 12, 2022, to December 31, 2023). Epidemiological characteristics of MP infections were assessed using descriptive statistics and regression analysis. Results Among the 15,718 patients, 5,454 (34.7%) tested positive for MP. The highest positivity rate was observed in children aged > 6 years (52.4%), with a male predominance across all age groups. Most infections occurred in autumn (41.5%). The MP positivity rate was lowest during the pandemic period and highest in the post-pandemic period ( P < 0.001). Regression analysis indicated a broadening of the susceptible age range following the pandemic onset. Conclusion COVID-19 containment measures altered the transmission dynamics of MP, affecting demographic characteristics such as age distribution and seasonal trends. Continuous surveillance of MP epidemiology in the post-pandemic era is recommended to inform clinical management and public health strategies.
RAF1 as a standalone therapeutic target in KRAS-driven lung adenocarcinoma: No added efficacy from co-targeting ARAF, EGFR, or DDR1
Background/objectives KRAS-mutant lung adenocarcinoma remains without effective targeted therapies for most patients, particularly those with non-G12C alleles or resistance to KRAS G12C inhibitors. RAF1 is essential for KRAS-driven tumor maintenance through kinase-independent survival functions, making it an attractive candidate for targeted protein degradation. However, the therapeutic impact and safety of co-targeting RAF1 with related kinases remain unclear. Methods We used dual-recombinase genetically engineered mouse models of Kras +/G12V ;Trp53 -/- lung cancer to evaluate the effects of Raf1 ablation alone or in combination with Araf , Egfr , or Ddr1 . Lung tumors were initiated by intranasal Ad5-CMV-FLPo delivery and allowed to reach CT-detectable size before inducing systemic gene deletion via tamoxifen-activated CreERT2. Tumor burden was monitored by longitudinal CT imaging and classified using RECIST-like criteria. Toxicity was assessed by body weight monitoring, histopathology of major organs, and survival analysis. Results Raf1 deletion induced robust tumor regression within two months, in more than 60% of lesions. Araf ablation alone or combined with Raf1 did not affect tumor initiation, progression, or regression rates. Similarly, neither genetic nor pharmacological EGFR inhibition (afatinib) improved responses to Raf1 ablation. Ddr1 co-deletion also failed to enhance therapeutic efficacy and slightly reduced response rates. None of the dual-targeting strategies increased systemic toxicity. Conclusions RAF1 is a key, non-redundant vulnerability in KRAS-driven lung adenocarcinoma. Co-targeting ARAF, EGFR, or DDR1 provides no additional therapeutic benefit in established disease. The absence of adverse effects from ARAF co-deletion suggests that RAF1 degraders with partial cross-activity towards ARAF are likely to be safe. These findings provide a strong preclinical rationale for developing RAF1-targeted degradation as a monotherapy for these malignancies.
Development of engineered magnetic liposome/exosome hybrid as a novel caffeine nanocarrier for restraining liver fibrosis induced in rats
Abstract Liver fibrosis, a severe health issue linked to liver injury, inflammation, and cell death, often progresses to liver cancer without effective treatments. In this study, an exosome-nanoliposome hybrid loaded with caffeine (Caff) was developed for the management of liver fibrosis. The role of superparamagnetic iron oxide nanoparticles (SPION) in promoting targeted delivery to the liver was also investigated. Caff-loaded liposomes with variable phospholipid and stearylamine molar ratios were prepared and characterized. The formula with optimized characteristics (Caff/liposomes) selected by Design Expert exhibited a particle size of 179.73 ± 3.1 nm, a polydispersity index of 0.19 ± 0.02, an entrapment efficiency of 89.79 ± 21%, and a zeta potential of -35.50 ± 1.1 mV, and was used to encapsulate SPION. Caff/SPION liposomes were further loaded into exosomes, isolated from bone marrow-mesenchymal stem cells, and visualized by TEM. The biological experiment was conducted on rats with thioacetamide-induced liver injury to reveal the efficacy of exosome-Caff/SPION liposome hybrid (F1) in comparison to exosome-Caff/liposomes (F2) and exosome-SPION/liposomes (F3). Among all the tested formulations, F1 demonstrated the most promising results regarding liver function markers (ALT and AST), inflammatory molecules (IL-6, IL-10, TLR-4, Myd88, NF-κB), fibrotic protein (α-SMA), hepatocyte proliferative capacity (PCNA), as well as liver histoarchitecture. This finding suggests that the engineered Caff/SPION liposome-exosome hybrid can effectively enhance the targeting of the drug and the homing of exosomes to the injured liver, thereby representing a novel strategy for treating liver fibrosis.
Genetic ablation of interleukin-17A augments fibrosis in a mouse model of cholestatic liver injury
Aim The underlying mechanisms contributing to cholestatic liver injury remain unclear. The pro-inflammatory leukocyte-restricted cytokine interleukin-17A (IL-17A) has been implicated in human cholestatic liver injury. However, mechanistic insights are lacking and require further exploration in preclinical models. Herein, we examined the effect of IL-17A genetic ablation in a mouse model of cholestatic liver injury. Method Age and gender-matched littermate wild type (WT) and Il-17a -/- C57BL/6 mice were fed an intermittent 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 21 days to induce cholestatic liver injury or a control diet. Results As compared to WT littermates, Il-17a -/- mice displayed more abundant desmin-positive myofibroblasts and increased fibrosis. NanoString analysis of intrahepatic leukocyte populations using a fibrosis-related gene panel identified upregulation of Tnfsf14 (encoding the protein LIGHT) in the DDC-fed Il-17a -/- mice. Although mass cytometry identified an increase in myeloid cells in both genotypes of the DDC-fed mice, we could not identify LIGHT expression in this cell lineage. Instead, the upregulation of LIGHT expression was largely restricted to a CD4 + T cell population as assessed by flow cytometry. Enhanced LIGHT expression was observed in a Th1 + CD4 + T cell population. LIGHT activated primary human hepatic stellate cells in vitro, suggesting that LIGHT stimulation of hepatic fibrogenesis may be direct. Conclusion Taken together, these data suggest that IL-17A restrains expression of the profibrogenic cytokine, LIGHT, by Th1-polarized CD4 + T cells, and implicate a role for LIGHT in cholestatic fibrogenesis in DDC-fed mice; a finding which requires validation in additional models.
Correction: Experimental and machine learning-based analysis of red mud influence on recycled aggregate concrete properties
A multifaceted analysis of OTUD5 integrated MAVS in innate immunity of Primary Biliary Cholangitis
Background Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis caused by intrahepatic small bile duct injury. Promoting the molecular mechanism of OTU deubiquitinase 5 (OTUD5) in the treatment of PBC requires further exploration. This study unraveled the molecular underpinnings of PBC through bio-informatics analysis and experimental verification for the development of targeted therapeutic strategies. Methods This study screened immune-related genes and validated their expression patterns in whole blood of patients with PBC using microarray based on GEO datasets. The expression level of OTU deubiquitinase 5 (OTUD5) was validated in peripheral blood samples using RT-qPCR and immunofluorescence. Subsequently, proteomic bioinformatics analyses were conducted utilizing STRING and InBio Discover databases to predict interactions with the mitochondrial antiviral signalling protein (MAVS). Furthermore, immunochemical and immunofluorescence analyses of MAVS expression in liver tissues were conducted with a thorough analysis of immune cell infiltration specific to the disease by utilizing single-cell RNA sequencing (scRNA-seq) technology in peripheral blood mononuclear cells (PBMCs) derived from both patients with PBC and healthy controls. Results Compared with those of healthy controls, the liver tissues of patients with PBC presented increased NK cell activation, monocyte/mast cell numbers, and eosinophil numbers. Compared with those in 10 healthy controls, the expression of OTUD5 and MAVS was increased in 16 tissues of patients with PBC. High expression of OTUD5-MAVS in subpopulation 11 mononuclear macrophages was screened by PBMC scRNA-seq, and mononuclear cells with the subgroup 11 phenotype presented highly differentiated characteristics. The expression of OTUD5 and MAVS was inhibited in RAW264.7 cells when OTUD5 was knocked down (P < 0.05). Conclusion This study focused on the overexpression of OTUD5 and its interaction with MAVS within macrophage subset 11 in patients with primary biliary cholangitis (PBC). The expression of OTUD5 and MAVS is increased in patients with PBC and is a potential target for the diagnosis and treatment of PBC.
Pituitary lesions in captive chimpanzees (Pan troglodytes): clinical presentation and histologic characterization
Eccentric cycling is superior to standard rehabilitation for Post-ICU recovery in COVID-19 survivors
Background The COVID-19 pandemic left numerous patients with post-intensive care syndrome (PICS) that resulted in prolonged physical and health impairment. Compared to standard rehabilitation (STD REHAB), eccentric cycling (ECC) has lower cardiopulmonary demands while inducing greater functional performance improvements after training, which could be ideal for individuals with PICS. Aim To compare the effects of eight weeks of ECC versus STD REHAB on functional performance and quality of life of patients after hospitalization. Methods Randomised crossover design study (clinicaltrial.gov: NCT06895850). Twenty survivors of the COVID-19 infection (50.8 ± 8.8 years old) recruited six months after hospitalization were involved. Participants were initially randomized into ECC (n = 10) or STD REHAB (n = 10). Both groups trained for eight weeks, rested for two weeks, and performed the crossover with the remaining training modality. Exercise time was 20−30 min for ECC and 60 min for STD REHAB. Cardiopulmonary demand was measured during training. Body composition, whole-body manual and handgrip strength, functional performance (6-min walking test; 6MWT, timed up and go; TUG, 1-min sit to stand), cognitive (MoCa and Barthel Index), and quality of life and symptoms (QoL; Patient Health Questionnaire; PHQ and Post-COVID-19 Functional Status Scale; PCFS) were measured before and after interventions. Results Cardiopulmonary demand during training was lesser during STD REHAB than ECC. All variables improved after both interventions, but ECC showed larger improvements in 6MWT, TUG, and Barthel Index compared to STD REHAB. Conclusion Eccentric cycling training induced greater functional and cognitive improvements than standard rehabilitation.
Structure-based modeling reveals molecular basis for CYP153A6’s novel activity toward toluene derivatives
Abstract CYP153A6 from Mycobacterium sp. strain HXN-1500 is a monooxygenase that catalyzes the selective hydroxylation of terminal methyl groups in various alkanes. This study explored CYP153A6 activity towards a set of toluene derivatives, along with the underlying molecular recognition. Initial in vivo evaluation of CYP153A6 activity, conducted using both whole cells and cell-free extracts, showed efficient conversion of toluene derivatives with apolar or slightly polar substituents, while no detectable activity was observed for derivatives bearing more polar groups. A homology model of CYP153A6 3D structure was built and validated, revealing key structural features and molecular tunnels. An ensemble docking strategy was used to identify the most effective docking setup. Molecular dynamics simulations and binding free energy calculations further confirmed the hydrophobic nature of the active site. QM/MM calculations supported the different reactivity observed between p-chlorotoluene and p-nitrotoluene. Toluene derivatives bearing a hydroxyl or nitro group on the aromatic ring exhibit reduced binding affinity, adopting unfavorable orientations and non-productive distances between the methyl group and the enzyme’s heme iron center. These computational findings agree with experimental data. Overall, this study provides valuable insights into CYP153A6 molecular recognition mechanism and lay a strong foundation for future protein engineering to extend CYP153A6 enzyme substrate scope and/or enhance the product yield.
Screening a library of antibacterial compounds leads to discovery of novel inhibitors for Neisseria gonorrhoeae and Chlamydia trachomatis
Chlamydia trachomatis and Neisseria gonorrhoeae were the most common bacteria causing sexually transmitted infections (STIs) in 2020, with 211 million cases worldwide. Despite the fact that the co-infections of N. gonorrhoeae with C. trachomatis are common, there is no single treatment effective against both pathogens. Ceftriaxone, the current recommended drug for gonococcal infections , is not effective against C. trachomatis . Additionally, N. gonorrhoeae has developed resistance against the drugs recommended for treating chlamydial infections. Therefore, new drugs capable of treating C. trachomatis / N. gonorrhoeae co-infections are needed. Drug repurposing is an attractive, fast-track approach for antimicrobial drug discovery. In an attempt to address the unmet need for development of C. trachomatis / N. gonorrhoeae therapeutics utilizing the drug repurposing approach, we screened the antibacterial compounds library against N. gonorrhoeae . This library encompasses a unique collection of 1,128 bioactive compounds with validated antibacterial activities . A total of 172 active hits were identified, and then repeated drugs with different salts or previously reported drugs were excluded before determining the minimum inhibitory concentrations (MICs) against N. gonorrhoeae FA1090. Thereafter, the anti- C. trachomatis activities of the 14 selected drugs were assessed. We identified gloxazone and SPR719 as promising agents with potent activities against both C. trachomatis and N. gonorrhoeae (MICs ≤ 1 µM) . Collectively , SPR719 and gloxazone could be considered promising agents warranting further investigation to address the unmet need in the treatment of bacterial STIs.
Problematic internet users develop enhanced perceptual processing to offset neural deficits in conflict monitoring
Monte Carlo dosimetric characterization of the IRAsource high dose rate Iridium-192 brachytherapy source: Comparison with the mHDR-v2r model
The aim of this study was to evaluate the dosimetric characteristics of an IRAsource brachytherapy source using Monte Carlo simulations incorporating source electron effects. The dose rate constant, radial dose function, and two-dimensional (2D) anisotropy function were calculated and compared with those of published data and results of the mHDR-v2r source model. The dose rate constant obtained for the IRAsource was ( 1.1142 ± 0.0030 ) c G y h − 1 U − 1 , which was consistent with previously reported values, within the range of experimental uncertainty. The radial dose function exhibited a pattern similar to that of the mHDR-v2r source, with dose distributions converging at distances of approximately 10 cm, where the effect of capsule thickness became negligible. The 2D anisotropy function did not fully align with other experimental datasets for the IRAsource. Even when comparing the IRAsource with mHDR-v2r sources, the 2D anithotropy function showed a difference of 3% to 6% around 0 degrees at distances of 0.25 cm to 5.0 cm from the source. The results reflected reasonable trends that were consistent with differences in source capsule geometry of the IRAsource and the mHDR-v2r. These findings show that the dosimetric data presented here is reliable. This study provides essential baseline data for accurate dose assessment of the IRAsource in brachytherapy and underscores the importance of further experimental validation to refine dose characterization.
Emotion-specific vocabulary is associated with preschoolers’ emotion knowledge and behavioral emotion regulation
Abstract Language supports emotional development by enabling children to mentally represent conceptual emotion knowledge. Whereas previous research has linked emotion-specific vocabulary to emotion knowledge, its role in emotion regulation (ER) performance remains unclear. In this cross-sectional study we examined 197 German preschoolers aged 4–6 years (M = 5.6), all typically developing; for 10 children, parents reported exposure to an additional home language besides German. We investigated how general and emotion-specific vocabulary relate to preschoolers’ emotion knowledge (i.e., emotion recognition and knowledge of ER strategies) and their ability to regulate positive and negative emotional expressions. We further examined whether emotion knowledge mediates the link between language and ER. Results showed that, beyond general vocabulary, the size (number of words) and depth (adult-like use) of emotion-specific vocabulary interacted in predicting emotion knowledge and regulation of positive emotions. Different patterns emerged for emotion knowledge and ER. Regarding emotion knowledge, high emotion-specific vocabulary depth compensated for low size, whereas high emotion-specific vocabulary size supported regulation of positive emotions only when paired with high depth. No such effects emerged for the regulation of negative emotions. No mediating role of emotion knowledge was found. Findings suggest that a deeper understanding of emotion concepts—beyond merely knowing many emotion words—may be particularly crucial for the regulation of positive emotions.
Activity driven sleep dynamics: A conceptual modeling study
The sleep state is traditionally defined as global, involving the entire body. Accordingly, a two-process mathematical model of the switch between sleep and wakefulness was proposed by Borbely more than 30 years ago and successfully used in deep modeling studies. However, in recent decades, new data have been obtained that call for a more complex understanding of sleep, both in spatial and temporal aspects. In particular, this concerns such phenomena as local sleep and short sleep episodes (naps). Here, we propose a mathematical model that gives the space for both local sleep phenomena and short sleep episodes. In doing so, we rely on the concept of a “sleep unit” and propose a phenomenological rate model of its activity. We also use a concept of a psycho-sensory drive to simulate various scenarios induced by external or internal stimuli. An essential element of our model is the representation of the background neural activity as a random signal, which reflects the real situation of overlapping multiple internal and external stimuli. The corresponding simulation runs confirm that the model reproduces both phenomena: local sleep and short nap episodes. As a particular but illustrative result, we demonstrate an example of involuntary global falling asleep under conditions of an overload of a separate sleep unit. In conclusion, we discuss the potential of our model and ways of its further quantitative parameterization.
Proton-pump inhibitors and palbociclib or abemaciclib in endocrine-sensitive breast cancer treatment
Telehealth during and beyond the COVID-19 Pandemic: Evidence from licensed dietitians in an emerging economy
Background The sudden onset of the SARS-Cov-2 (COVID-19) pandemic disrupted access to in-person nutrition consultation and prompted the rapid adoption of telehealth by dietitians. Objective This study investigates the use of telehealth among Lebanese Licensed Dietitians (LDs) during COVID-19, in the absence of national telehealth practical guidelines (TPG), and offers insights into its application amid overlapping crises including a pandemic, economic crisis, and infrastructure disruption in Lebanon. Design A cross-sectional study conducted in March 2023, using an anonymous 44-question online survey, distributed via the Lebanese Order of Dietitians and social media platforms. Participants: Ninety-four dietitians participated (98.9% female, mean(SD) age: 30.54(6.41) years); mean(SD) experience: 7.89(5.7) years). Most reported practicing clinical nutrition as their primary practice area (87.2%), primarily in weight management (84%). Main outcome: Measures included Dietitians’ experience with telehealth, tools used in remote consultations, perceived barriers and facilitators, and perspectives on future application. Statistical analyses: Descriptive analysis (counts, frequencies) were analyzed using SPSS version 28. Results Telehealth use rose from 48.4% before COVID-19 to 97.8% during it. Commonly used platforms included WhatsApp (90.3%), Zoom (72.0%), and e-mails (41.9%). Reported barriers included bad internet connection (74.2%), patients preferring face-to-face consultation (61.3%), and patients unfamiliar with emerging videoconferencing technologies (33.3%). Benefits included scheduling and time flexibility (83.9%), decrease in practice-related costs (77.4%), and compliance with social distancing measures (53.8%). Most respondents acknowledged that Telehealth is needed (78.5%) and applicable in the Lebanese context (64.6%) and called for telehealth trainings (78.5%) and national TPG development (74.2%). Conclusion This study recognizes the growing use of telehealth in Lebanon, underscoring the need for telehealth with national regulations and evidence-based guidelines. Despite limited infrastructure, LDs continued delivering care, emphasizing the urgency for secure and standardized frameworks to support ethical and sustainable digital health practice.