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Barriers and facilitators to palliative care service utilization in Ethiopia: A qualitative systematic review, 2025
Introduction Palliative care is a crucial component of end-stage disease management, but its utilization remains low in low- and middle-income countries, such as Ethiopia. This is due to various systemic, social, and policy barriers. Understanding these contextual factors is crucial for developing effective interventions and policy frameworks. This study aimed to explore and synthesize the barriers and facilitators to palliative care service utilization in Ethiopia using a qualitative systematic review approach. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Qualitative Synthesis (PRISMA-Q) guidelines, employing a qualitative systematic design. A comprehensive search was conducted across various databases using tailored keywords and MeSH terms up. The database was searched for every article published on palliative care services up to March 10, 2025, and was updated continuously until it was sent for publication. The data was extracted from March 11–20 and later analyzed from March 21–30, and the report generation till April 10, 2025. Thematic synthesis was used to analyze findings and the Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative research approach was employed to assess the confidence of evidence. Results Six studies met the inclusion criteria, encompassing diverse Ethiopian healthcare settings and stakeholders. Five major barriers were identified: policy and governance gaps, health system challenges, knowledge and training deficits, sociocultural and economic constraints, and poor collaboration. In contrast, five facilitators emerged: strong community and family support, intrinsic healthcare provider motivation, integration of palliative care into education, holistic care models, and stakeholder engagement. High confidence was assigned to four themes, underscoring their significance and applicability. Conclusion The underutilization of palliative care in Ethiopia stems from intertwined structural, educational, and sociocultural challenges. However, promising facilitators exist that can guide policy reform and intervention design. Addressing these barriers through improved policies, workforce development, and community engagement is imperative for ensuring equitable access to quality palliative care services.
Neuroimaging insights into recent suicide attempters utilizing the raven task
Background Understanding brain function in individuals who have recently attempted suicide is critical for improving diagnosis and treatment strategies. This study aimed to examine neural activity patterns in such individuals (who had attempted suicide 1–4 weeks before the study) using functional magnetic resonance imaging (fMRI) and the General Linear Model (GLM). Methods Sixty participants were recruited and categorized into three groups: individuals with a recent suicide attempt and Major Depressive Disorder (SA + MDD), individuals with Major Depressive Disorder without a suicide attempt (MDD), and healthy controls (HC). Participants performed the Raven task, consisting of 24 trials with a 25-second time limit for each item. Brain activity was analyzed to identify regional differences among groups using ANOVA, followed by Tukey’s post-hoc pairwise comparisons. Results Compared to the MDD and HC groups, the SA + MDD group exhibited significantly reduced activation in the left medial superior frontal cortex (SFC), left anterior cingulate cortex (ACC), and left precentral gyrus. Positive correlations were observed between the Scale for Suicidal Ideation scores and activity in the medial SFC and ACC, whereas a negative correlation was found with precentral gyrus activity. While task accuracy did not significantly differ among the groups, the SA + MDD group demonstrated significantly shorter response durations. Conclusion Individuals with recent suicide attempts show diminished activation in key left-hemispheric regions involved in cognitive control and problem-solving, including the medial SFC, ACC, and precentral gyrus. These neural deficits may impair decision-making and problem-solving abilities, particularly when compounded by hopelessness and a diminished sense of purpose, potentially contributing to increased suicide risk.
Correction: Accelerating automatic model finding with layer replications case study of MobileNetV2
Correction: It’s not all abundance: Detectability and accessibility of food also explain breeding investment in long-lived marine animals
Prognostic prediction of dengue hemorrhagic fever in pediatric patients with suspected dengue infection: A multi-site study
Dengue virus (DENV) infection is a major global health problem. While DENV infection rarely results in serious complications, the more severe illness dengue hemorrhagic fever (DHF) has a significant mortality rate due to the associated plasma leakage that may lead to hypovolemic shock. Proper care thus requires identifying patients with DHF among those with suspected dengue so that they can be provided with adequate and prompt fluid replacement. In this study we used seventeen years of pediatric patient data from a prospective cohort study in two hospitals in Thailand to develop models to predict DHF among patients with suspected dengue infection. We produced models for a general hospital setting and for a primary care unit setting lacking lab facilities. The best model using combined data from both hospitals achieved an AUC of 0.90 for the general hospital setting and 0.79 for the primary care unit setting. We then investigated the generalizability of the models by training models with data from one hospital and testing them with data from the other. For some models, we found a significant reduction in performance. Possible sources of this are differences in how attributes are defined or measured and differences in the hematological parameters of the two patient populations. We conclude that while high accuracy prediction of DHF is possible, care must be taken when applying DHF predictive models from one clinical setting to another.
Loneliness and delusion-like experiences among women: Mediating role of procrastination and boredom proneness
Delusions, a core psychopathological symptom, occur both in mental disorders and as delusion-like experiences in the general population. This study aimed to examine the relationship between loneliness and delusion-like experiences, considering the mediating roles of procrastination and boredom proneness. The sample consisted of 291 women aged 18–65 years (M = 30.05; SD = 10.298). The analyses revealed that procrastination (Indirect = 0.05; 95%CI [0.01; 0.10] significantly mediated the relationship between loneliness and delusion-like experiences, while boredom proneness showed no significant mediating effect (Indirect = 0.02; 95%CI [−0.01; 0.04]). These findings suggest that procrastination may be a key mechanism underlying the association between loneliness and delusions, with potential implications for therapeutic interventions. The results obtained may serve as a foundation for implementing effective interventions to reduce belief in delusions, stress associated with experiencing delusions, and preoccupation with delusional thoughts. Moreover, understanding the functioning of individuals with delusion-like experiences may support the adaptation of specific therapeutic and support techniques.
Correction: Steatosis is involved in the progression of kidney disease in a high-fat-diet-induced non-alcoholic steatohepatitis mouse model
CRISPR/Cas9-targeted smpB mutation revealing roles in biofilm formation, motility, and antibiotic susceptibility in Acinetobacter baumannii
Background Acinetobacter baumannii is a multidrug-resistant pathogen and a major cause of hospital-acquired infections worldwide. Its ability to survive in harsh environments and evade antibiotic treatments underscores the urgent need for new therapeutic targets. Emerging evidence suggests that the small protein B (SmpB) may also play broader roles in bacterial virulence, including regulation of biofilm formation, motility, and stress adaptation. However, the specific contributions of SmpB to these pathogenic traits in A. baumannii remain poorly defined. Addressing this knowledge gap is essential for evaluating SmpB as a potential antimicrobial target and developing new strategies to combat multidrug-resistant infections. Methods CRISPR/Cas9-mediated gene editing was used to generate a targeted smpB mutant in A. baumannii. The smpB mutant was assessed for growth, biofilm formation, motility, antibiotic susceptibility, and virulence. Biofilm was quantified via crystal violet staining and microscopy, while motility was examined using swimming, swarming, and twitching assays. Antibiotic susceptibility was evaluated using disk diffusion. Virulence was tested in the Galleria mellonella infection model. Proteomic analysis was performed to identify changes in protein expression associated with smpB disruption, Results CRISPR/Cas9-mediated editing successfully introduced a C212T nucleotide substitution in the smpB gene, resulting in an A89G amino acid change. Growth curve analysis showed no significant difference between the wild-type and smpB mutant strains under nutrient-rich conditions. However, the mutant exhibited a significant reduction in biofilm formation (p = 0.0079) and impaired twitching motility, while swimming and swarming motility remained unaffected. Antibiotic susceptibility testing revealed increased sensitivity to ceftizoxime, piperacillin/tazobactam, and gentamicin, alongside decreased susceptibility to cefepime, tetracycline, and spectinomycin. In the G. mellonella infection model, the smpB mutant showed reduced virulence, with 84% larval survival compared to 72% in the wild type (p = 0.4183). Proteomic analysis revealed downregulation of key stress response and virulence-associated proteins, including GroEL, DnaK, RecA, and PirA, while proteins involved in ribosome maturation and transcription, such as RimP and RpoA, were upregulated. STRING network analysis supported the broad regulatory role of SmpB in biofilm formation, motility, stress adaptation, and pathogenesis. Conclusion This study demonstrates that SmpB is a key regulator of biofilm formation, twitching motility, antibiotic response, and virulence in A. baumannii. While not essential for growth under optimal conditions, smpB disruption impairs multiple pathogenic traits and alters stress-related proteomic pathways. These findings highlight the potential of SmpB as a novel antimicrobial target, offering a promising strategy to weaken bacterial virulence without promoting resistance. Targeting the trans-translation system may pave the way for innovative therapies against multidrug-resistant A. baumannii.
Artesunate regulates malignant progression of breast cancer cells via lncRNA TUG1/miR-145-5p/HOXA5 axis
Background Breast cancer continues to be a predominant cause of female mortality globally, characterized by limited therapeutic options and substantial adverse effects. Artesunate (ART), a traditional Chinese medicine approved by the FDA for malaria treatment, has demonstrated potential anticancer properties against breast cancer. However, the underlying molecular mechanisms remain incompletely elucidated. This study posits that the antitumor efficacy of artesunate may be mediated through the regulation of the lncRNA TUG1/miR-145-5p/HOXA5 axis. Methods A comprehensive array of in vitro assays was employed to investigate the proposed molecular pathway, including CCK-8 proliferation assay, EdU incorporation assay, Transwell invasion assay, scratch wound healing assay, TUNEL apoptosis assay, and dual-luciferase reporter assay. Additionally, Western blot analysis, quantitative real-time PCR (qPCR), and plasmid transfection techniques were utilized to validate the findings. Results The results revealed that artesunate exerted a dose-dependent inhibitory effect on breast cancer cell proliferation. This was accompanied by the down-regulation of HOXA5, WNT, β-catenin, Fizz1, and Arg-1, implicating the involvement of the WNT/β-catenin signaling pathway. Furthermore, artesunate significantly modulated the expression levels of lncRNA TUG1, miR-145-5p, and HOXA5, suggesting a mechanistic role of the lncRNA TUG1 pathway in its anticancer activity. Conclusions These findings indicate that artesunate may inhibit breast cancer progression through the lncRNA TUG1/miR-145-5p/HOXA5 axis, highlighting its potential as a promising therapeutic candidate for future clinical trials in cancer therapy.
Correction: Subjective and psychophysical olfactory and gustatory dysfunction among COVID-19 outpatients; short- and long-term results
MilkOligoCorpus: A semantically annotated resource for knowledge extraction on mammalian milk oligosaccharides
Milk oligosaccharides are bioactive components that regulate the composition of the neonatal microbiota and exert immunomodulatory functions. Their beneficial effects depend on their structure. Numerous studies have shown intra- and inter-species variation in the structural composition and concentration of these compounds in mammalian milk, yet the biological significance of such variation remains poorly understood. Automated natural language processing methods are promising tools for extracting and gathering structured data from unstructured texts to get insight into the biological significance of milk oligosaccharide variation across mammals. These methods require training and evaluation on manually annotated text corpora. While annotated corpora exist for chemical substances, none are specifically designed for training natural language processing models to extract information on milk oligosaccharides. To this end, we propose MilkOligoCorpus, a new gold standard for milk oligosaccharide composition in mammalian species. MilkOligoCorpus’ annotation scheme is a rich entity/relation model designed to describe the diversity pattern of milk oligosaccharides according to female factor variability and to help better understand the structure-related function of milk oligosaccharides. MilkOligoCorpus consists of abstracts (15) and extracts (15) from 20 full text articles indexed by PubMed annotated with entities related to individuals, samples, oligosaccharides and oligosaccharide quantification linked by binary and n-ary relationships. To address data interoperability across disparate publications and databases, four terminological resources were also developed to assign unique identifiers to the entities, supported by external ontologies. This paper presents the creation of the MilkOligoCorpus and its associated schema, along with the development of annotation guidelines and terminological resources. We also present experimental results obtained by baseline information extraction models on the corpus.
Corneal sensory nerve loss induced by repeated subconjunctival and topical bupivacaine disrupts tear secretion and enhances bacterial adhesion via neuropeptide modulation
Purpose Corneal sensory innervation plays a crucial role in maintaining ocular surface integrity and immune homeostasis by regulating neuropeptide secretion in tear fluid. Sensory dysfunction disrupts tear production and neuropeptide signaling, increasing susceptibility to microbial infections. However, the mechanistic link between sensory nerve suppression, neuropeptide depletion, and bacterial adhesion remains incompletely understood. This study establishes a refined protocol for targeted corneal sensory nerve suppression using bupivacaine, a long-acting local anesthetic, and investigates the roles of substance P (SP) and calcitonin gene-related peptide (CGRP) in modulating tear production and bacterial adhesion. Method Male and female C57BL/6J (wild-type) mice (6–8 weeks old) were used to establish a localized and sustained corneal nerve suppression model via subconjunctival bupivacaine injection combined with topical application every other day for 15 days. This approach ensured precise modulation of corneal sensory function. Using this model, we investigated how sensory denervation influences microbial adhesion dynamics for Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, three clinically relevant pathogens with distinct adhesion mechanisms. Bacterial inoculation was standardized using the Kimwipe blotting method to achieve uniform deposition onto the corneal surface, followed by quantification of bacterial adhesion. Tear production was assessed using SMTube testing to evaluate nerve depletion-associated alterations. Enzyme-linked immunosorbent assay (ELISA) was used to quantify SP and CGRP levels in tear fluid, determining whether their depletion correlated with increased bacterial adhesion and altered tear production. To assess whether neuropeptide restoration mitigates bacterial adhesion, SP, CGRP, or phosphate-buffered saline (PBS; control) was administered via subconjunctival injection prior to bupivacaine treatment on day 14 and 15 during the experimental timeline. All assessments, including nerve depletion effects on tear production, bacterial adhesion, and neuropeptide loss, were conducted on day 15 post-bupivacaine treatment. Results Targeted corneal sensory denervation via combined subconjunctival and topical bupivacaine resulted in a ~ 50% reduction in corneal nerve density, achieving deeper and more localized nerve suppression compared to subconjunctival injection alone (P < 0.0001). This approach led to a 2.3-fold (~56.6%) reduction in tear production without inducing epithelial damage (P < 0.0001). This loss of sensory input led to a marked decrease in SP and CGRP levels in both the cornea and tear fluid, with the most pronounced reduction observed in the combined treatment group. Notably, neuropeptide depletion correlated with increased bacterial adhesion, with a ~ 1.18-fold increase for S. aureus and ~1.20-fold for P. aeruginosa, highlighting the critical role of corneal sensory nerves in modulating ocular surface immunity (P < 0.0001). Exogenous SP or CGRP supplementation restored neuropeptide levels and CGRP supplementation reversed bacterial adhesion, highlighting their critical function in maintaining antimicrobial defense. Conclusion This study establishes a novel, controlled model of corneal sensory denervation, revealing a direct link between neuropeptide depletion, impaired tear production, and increased microbial adhesion. By simulating neuropathic conditions such as diabetic keratopathy and neurotrophic keratitis, this approach provides a valuable framework for investigating neuroimmune interactions in ocular infections. Beyond infection models, this subconjunctival injection strategy serves as a versatile platform for studying ocular drug pharmacokinetics, neuroprotective interventions, and immune modulation.
Evaluating the scope and impact of pre-diagnostic manipulative therapy in children and adolescents with osteosarcoma: A retrospective study in Uganda
Background Pre-diagnosis manipulative therapies in patients diagnosed with osteosarcoma can compromise patients’ outcomes. Limited literature exists on the pre-diagnosis non-oncological management of osteosarcoma, especially in resource-limited settings. We described and characterized the practice of pre-diagnosis manipulative therapy at the reference cancer treatment center in Uganda as a first step to improving the quality along the osteosarcoma treatment pathway. Methods We reviewed the demographic and clinical characteristics, pre-referral management, and outcome of children under 18 years treated for osteosarcoma at the Uganda Cancer Institute between January 2016 and December 2020. Data on pre-diagnosis management were extracted, as well as clinical and disease characteristics and outcome. Descriptive statistics and Kaplan-Meier survival analysis were used. Results Nineteen (25.7%) of the 74 children with osteosarcoma in the current study had undergone prior manipulative therapy. The main forms of manipulative therapy were local therapeutic cuttings with the application of local herbs in 6 (31.5%) patients, massaging in 5 (26.3%), attempted incision and drainage in 4 (21.1%), and treatment as a local infection (osteomyelitis or arthritis) in 4 (21.2%). The majority, 15 (78.9%), of the patients who had manipulative therapy were males (X² = 5.73; p = 0.031). Children who underwent manipulative therapy were referred after a median of 45 days (range 11–139) compared to their counterparts, who were referred after a median of 28 days (range 1–147) (p = 0.012). Patients with manipulative therapy had a metastatic rate of 77.8%, while the rate was 60.4% for those who did not have manipulative therapy. The serum lactate dehydrogenase level was higher in patients who had manipulative therapy compared to those who did not have manipulative therapy (X2 = 3.98; p = 0.046). The median survival was 1.0 year (95% CI 0.8–1.3) for patients who underwent prior manipulative therapy and 1.8 years (95% CI 1.4–2.2) for those who did not report any form of manipulative therapy (p = 0.961). Conclusion Pre-diagnosis manipulative therapies lead to poorer outcomes in patients diagnosed with osteosarcoma, underscoring the need for bridging the quality gap in the osteosarcoma treatment pathway. This should include sensitization of the community and healthcare provider’s, strengthening patient referral pathways, and improved accessibility to cancer treatment centers.
Injury reporting in elite ladies Gaelic football and camogie: Perspectives of athlete support personnel
Objectives This study investigates athlete support personnel’s (ASP) perspectives on injury reporting among elite ladies’ Gaelic football and camogie players. ASP refers to individuals in coaching, management, and allied health and performance related practice. Methods A mixed-methods design was employed, comprising an online survey and follow-up interviews. Forty-two ASP, currently or recently (within two years) involved in elite ladies’ Gaelic games, completed the survey. Eighteen ASP subsequently participated in semi-structured interviews. Quantitative survey data were analysed using frequency analysis, while interview transcripts were subjected to framework analysis. Results A significant proportion of ASP (43%, n = 18) believe that players do not report all injuries. Most respondents (95%, n = 40) agreed that players often avoid reporting injuries to prevent losing playing time, while 95% (n = 40) cited player fear of being side-lined as a key factor. Furthermore, 93% (n = 39) agreed that players are more likely to report injuries when immediate access to medical personnel, such as team doctors or physiotherapists, is available. Notably, 66% (n = 28) disagreed with the perception that managers view players as weak for reporting injuries, while 19% (n = 8) agreed with this notion. Qualitative findings corroborated these results and identified three overarching themes influencing injury reporting: player factors, system-driven influences, and environmental conditions. Individual factors included a competitive environment that prioritised maintaining team position over health, with experienced players exhibiting greater confidence in reporting injuries compared to younger players, who often perceived management as hierarchical and less approachable. Immediate, consistent access to physiotherapists and other medical professionals was highlighted as a critical enabler of injury reporting. Trust in ASP, built through visible involvement and positive relationships, emerged as a key determinant. Additionally, a supportive team culture that prioritises player well-being alongside performance outcomes was identified as essential for encouraging open injury reporting. Conclusion Injury underreporting is a significant issue among elite ladies’ Gaelic games players, driven by personal, system-level, and environmental factors. Of critical importance for teams and organisations is to provide education for players and ASP on the importance and value of injury reporting to support early and appropriate intervention. Concurrently providing improved medical access will help to foster stronger, trust-based relationships between players and ASP, considered crucial for improving injury reporting practices.
Adipose-derived mesenchymal stem cells and retinal pigment epithelial cells interactions in a stress environment via tunneling nanotubes
This study aims to demonstrate the formation of tunneling tubes (TNTs) between adipose-derived mesenchymal stem cells (AdMSCs) and retinal pigment epithelial cells (RPE-1) and their alterations in response to experimental stress conditions. Serum starvation was employed as a stress condition to induce TNTs between the AdMSC and RPE-1 cells. The presence of TNTs was demonstrated through immunofluorescence microscopy, while scanning electron microscopy was utilized to determine the average thickness. Cell viability was assessed after stress by CellTiter-Glo, and H2DCFH-DA probes evaluated the cells’ reactive oxygen species (ROS) levels. Further, JC-1 labelled mitochondrial exchange between cells via TNTs was confirmed by time-lapse imaging. A transmembrane culture system was employed to inhibit TNTs. In this study, we investigated the role of TNTs in facilitating intercellular communication and mitochondrial transfer between AdMSCs and RPE-1 cells under stress. We found that TNT-mediated mitochondrial transfer from AdMSCs to RPE-1 helps to reduce ROS levels and improve cell viability. We demonstrated that direct interaction between AdMSCs and RPE-1 cells was crucial for stress recovery. Co-culture enhanced the viability and sustained the RPE-1 cells’ function after stress-induced damage. Mechanical inhibition of TNT formation decreased cell viability and elevated ROS levels, indicating the importance of TNTs in cellular protection. The findings can provide a new perspective on the therapeutic potential of stem cell-based therapy in protecting retinal pigment epithelium cells against stress-induced damage and promoting tissue regeneration.
Leveraging potential of limpid attention transformer with dynamic tokenization for hyperspectral image classification
Hyperspectral data consists of continuous narrow spectral bands. Due to this, it has less spatial and high spectral information. Convolutional neural networks (CNNs) emerge as a highly contextual information model for remote sensing applications. Unfortunately, CNNs have constraints in their underlying network architecture in regards to the global correlation of spatial and spectral features, making them less reliable for mining and representing the sequential properties of spectral signatures. In this article, limpid size attention network (LSANet) is proposed, which contains 3D and 2D convolution blocks for enhancement of spatial-spectral features of the hyperspectral image (HSI). In addition, limpid attention block (LAB) is designed to provide a global correlation of the spectral and spatial features through LS attention. Furthermore, the computational costs of LS-attention are less compared to the multi-head self-attention (MHSA) of the classical vision transformer (ViT). In the ViT encoder a conditional position encoding (CPE) module is utilized that dynamically generates tokens from the feature maps to capture a richer contextual representation. The LSANet obtained overall accuracy (OA) of 98.78%, 98.67%, 97.52% and 89.45%, respectively, on the Indian Pines (IP), Pavia University (PU), Salina Valley (SV) and Botswana datasets. Our model’s quantitative and qualitative results are considerably better than the classical CNN and transformer-based methods.
The impact of exclusive breastfeeding for 6 months and of complementary breastfeeding after 6 months on bone mineral density and bone remodeling
Objective The aim of this study was to evaluate the evolution of bone mass in exclusive breastfeeding mothers (EBF) for 6 months, and another cohort, who had also exclusively breastfed their children while concomitantly donating breast milk for 6 months (EBF+), with evaluation of their bone mass during the subsequent 6-month period of complementary breastfeeding. Methods A group of exclusive breastfeeding mothers (n = 38) were evaluated at 15 days and six months postpartum, and a second group of EBF-donors (EBF+) (n = 39) were evaluated at six months and one year postpartum. Bone mineral content (BMC) and density (BMD) were evaluated by bone densitometry (DXA) and bone turnover markers were determined: osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal telopeptide (S-CTX). Results There was a significant decrease in BMD in the lumbar spine (1.107 ± 0.109 and 1.075 ± 0.112 g/cm2; p < 0.001), total body (1.135 ± 0.086 and 1.119 ± 0.085 g/cm2; p < 0.001), and total proximal femur over the six months of EBF compared to the values obtained from the same EBF group at 15 days postpartum (mean percentage decreases in BMD of −3.4 ± 3.7% (p < 0.001) in lumbar spine, −2.5 ± 3.4% (p < 0.001) in total proximal femur, and −1.7 ± 1.9% (p = 0.001) in total body). For the group of EBF + who practiced complementary breastfeeding after 6 months, densitometric results indicated a tendency to incorporation of bone mass, with a mean percentage increase in BMD of 5.0 ± 3.9% for lumbar spine, and 1.6 ± 3.4% for total proximal femur. Conclusion There was a significant physiological mobilization of bone mineral density in the lumbar spine, total body, and total proximal femur after six months of EBF. In the EBF+ group, even with continued complementary breastfeeding, densitometric results were higher than those observed at 6 months, indicating a continuous increase over time.
Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with difficult treatment and poor prognosis, whose pathogenesis could be associated with the expression patterns of circular RNAs (circRNAs). Here, we aim to investigate the effects and mechanism of hsa_circ_0006834 on iCCA proliferation. At first, hsa_circ_0006834 was proved to suppress iCCA cells proliferation and induce autophagy following the construction of hsa_circ_0006834 vector. And hsa_circ_0006834 is negatively linked with the proliferation, migration and invasion of iCCA cells through autophagy. Subsequently, RNA pull-down and dual-luciferase reporter assays were performed to validate the hsa_circ_0006834-has-miR-637-NGFR regulatory network. It was demonstrated by qPCR and Western blot that hsa_circ_0006834 stimulates the AMPK-mTOR pathway and triggers autophagy via NGFR after si-NGFR was synthesized and transfected into iCCA cells. Ultimately, after the successful knockdown of AMPK, the role of the AMPK-mTOR pathway in hsa_circ_0006834 regulating autophagy and proliferation was verified. Taken together, our findings revealed that hsa_circ_0006834 activates the AMPK-mTOR pathway and autophagy to suppress iCCA proliferation by has-miR-637-NGFR network, indicating the potential of hsa_circ_0006834 as a biomarker for iCCA diagnosis and therapy.
Correction: Effects of social and environmental restrictions, and changes in alcohol availability in adolescents’ binge drinking during the COVID-19 pandemic
Average acceleration and intensity gradient of 9–11-year-old rural and urban Kenyan school-going children and associations with cardiorespiratory fitness and BMI: The Kenya-LINX project
Background Physical activity (PA) is crucial for children’s health, cardiorespiratory fitness (CRF) and weight status. However, research on the PA profiles of Kenyan children, especially between rural and urban areas, is limited. Method This study examined the PA profiles of 537 school-aged children (51.6% girls, 9–11-year-olds) from Nairobi City County, Kenya (urban setting), and Kitui County, Kenya (rural setting), using stratified multistage random cluster sampling. Participants wore an accelerometer (Axivity AX3) on their non-dominant wrist for 24 hours a day over seven days. Raw accelerations were extracted and averaged over a 5-s epoch (AvgAcc) to estimate PA volume. Intensity gradient (IG) was calculated as a standardised metric of PA intensity. Participants’ CRF was assessed by the 20-metre multistage fitness test. Anthropometric measurements (mass and stature) were taken to compute BMI z-scores. Results PA metrics varied by sex, weight, and CRF. Boys had higher AvgAcc (p < .001) and IG (p < .001) than girls. Healthy weight participants differed significantly in AvgAcc from overweight (p = .001) and obese (p = .001) groups and in IG from overweight (p = .039) and obese (p = .003). Participants with sufficient CRF and insufficient CRF differed significantly in AvgAcc (p < .001) and IG (p < .001). AvgAcc was negatively associated with BMI z-scores (β = −0.02, p < .001) and positively associated with CRF (β = 0.21, p < .001), independent of IG and other covariates. IG showed a significant negative association with BMI z-scores (β = −1.27, p = 0.003) and a significant positive association with CRF (β = 18.93, p < .001), dependent on AvgAcc. Conclusions This study introduces AvgAcc and IG metrics among Kenyan children. Urban children accumulate less PA volume and exhibit an inferior intensity profile, which is reflected in important health indicators (BMI and CRF). These findings will inform policy as well as targeted interventions to enhance children’s health in diverse contexts.