bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the potential regulatory interactions in rheumatoid arthritis through a comprehensive analysis of lncRNA-related ceRNA networks
Authors: Yang Mingyi , Su Yani , Zheng Haishi , Xu Ke , Yuan Qiling , Cai Yongsong , Aihaiti Yirixiati , Xu Peng
Published: October 2023

Objective

This study aimed at constructing a network of competing endogenous RNA (ceRNA) in the synovial tissues of rheumatoid arthritis (RA). It seeks to discern potential biomarkers and explore the long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axes that are intricately linked to the pathophysiological mechanisms underpinning RA, and providing a scientific basis for the pathogenesis and treatment of RA.

Methods

Microarray data pertaining to RA synovial tissue, GSE103578, GSE128813, and GSE83147, were acquired from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). Conducted to discern both differentially expressed lncRNAs (DELncRNAs) and differentially expressed genes (DEGs). A ceRNA network was obtained through key lncRNAs, key miRNAs, and key genes. Further investigations involved co-expression analyses to uncover the lncRNA-miRNA-mRNA axes contributing to the pathogenesis of RA. To delineate the immune-relevant facets of this axis, we conducted an assessment of key genes, emphasizing those with the most substantial immunological correlations, employing the GeneCards database. Finally, gene set enrichment analysis (GSEA) was executed on the identified key lncRNAs to elucidate their functional implications in RA.

Results

The 2 key lncRNAs, 7 key miRNAs and 6 key genes related to the pathogenesis of RA were obtained, as well as 2 key lncRNA-miRNA-mRNA axes (KRTAP5-AS1-hsa-miR-30b-5p-PNN, XIST-hsa-miR-511-3p/hsa-miR-1277-5p-F2RL1). GSEA of two key lncRNAs obtained biological processes and signaling pathways related to RA synovial lesions.

Conclusion

The findings of this investigation hold promise in furnishing a foundational framework and guiding future research endeavors aimed at comprehending the etiology and therapeutic interventions for RA.
The contribution of genetics to dental caries, oral habits and occlusal traits in Turkish twins: A comparative study
Authors: Oz Esra , Kırzıoglu Zuhal
Published: October 2023

Objective

The aims of this study were to investigate and compare the prevalence of dental caries and the frequency of oral habits, molar relationships and occlusal traits between children of multiple births, and singletons, and to determine the relative contributions of genetics and environmental factors to these parameters by using twin study design.

Methods

The study group consisted of 345 multiple births (34 monozygotic and 122 dizygotic twin pairs, 11 sets of triplets) and 345 singletons between the ages of 2 and 17. The prevalence of dental caries, and the frequency of tooth brushing, the children’s oral habits, molar relationships, and occlusal traits were recorded.

Results

The percentage of children who brushed their teeth more than twice daily was statistically significantly higher in multiple births than in singletons. Higher correlation coefficients were found in dental caries index, except for decayed, filled (df) (2–5 age group) and filled (f) (6–11 age group), in the monozygotic twin pairs compared to those in the dizygotic twin pairs. In children between the ages of 6 and 11 years, mouth breathing, bruxism, lip biting, and pencil biting were higher in singletons than in children of multiple births. There were statistically significant differences between children of multiple births and singletons, with increased overjet in the 2–5 year age group being observed.

Conclusion

When analyzing these parameters, environmental factors must also be investigated. Due to the low incidence of twin births, longitudinal follow-up studies with more twin pairs are necessary to determine whether these results are generalizable.
Associations between blood pressure control and clinical events suggestive of nutrition care documented in electronic health records of patients with hypertension
Authors: Williams April R. , Thomson Maria D. , Britton Erin L.
Published: October 2023

Background

Clinical events suggestive of nutrition care found in electronic health records (EHRs) are rarely explored for their associations with hypertension outcomes.

Methods

Longitudinal analysis using structured EHR data from primary care visits at a health system in the US from December 2017—December 2020 of adult patients with hypertension (n = 4,237) tested for associations between last visit blood pressure (BP) control (≤ 140 Systolic BP and ≤ 90 Diastolic BP) and ≥ 1 nutrition care clinical event operationalized as (overweight or obesity (BMI > 25 or 30, respectively) diagnoses, preventive care visits, or provision of patient education materials (PEM)). Descriptive statistics and longitudinal targeted maximum likelihood estimation (LTMLE) models were conducted to explore average treatment effects (ATE) of timing and dose response from these clinical events on blood pressure control overall and by race.

Results

The median age was 62 years, 29% were male, 52% were Black, 25% were from rural areas and 50% had controlled BP at baseline. Annual documentation of overweight/obesity diagnoses ranged 3.0–7.8%, preventive care visits ranged 6.2–15.7%, and PEM with dietary and hypertension content were distributed to 8.5–28.8% patients. LTMLE models stratified by race showed differences in timing, dose, and type of nutrition care. Black patients who had nutrition care in Year 3 only compared to none had lower odds for BP control (ATE -0.23, 95% CI: -0.38,-0.08, p = 0.003), preventive visits in the last 2 years high higher odds for BP control (ATE 0.31, 95% CI: 0.07,0.54, p = 0.01), and early or late PEMs had lower odds for BP control (ATE -0.08, 95% CI: -0.15,-0.01, p = 0.03 and ATE -0.23, 95% CI: -0.41,-0.05, p = 0.01, respectively).

Conclusions

In this study, clinical events suggestive of nutrition care are significantly associated with BP control, but are infrequent and effects differ by type, timing, and patient race. Preventive visits appear to have the most effect; additional research should include examining clinical notes for evidence of nutrition care among different populations, which may uncover areas for improving nutrition care for patients with chronic disease.
Distinct hybridization modes in wide- and narrow-ranged lineages of Causonis (Vitaceae)
Authors: Yu Jinren , Zhao Hong , Niu Yanting , You Yichen , Barrett Russell L. , Ranaivoson Rindra Manasoa , Rabarijaona Romer Narindra , Parmar Gaurav , Yuan Langxing , Jin Xiaofeng , Li Pan , Li Jianhua , Wen Jun , Chen Zhiduan , Lu Limin
Published: October 2023

Background

Explaining contrasting patterns of distribution between related species is crucial for understanding the dynamics of biodiversity. Despite instances where hybridization and whole genome duplication (WGD) can yield detrimental outcomes, a role in facilitating the expansion of distribution range has been proposed. The Vitaceae genus Causonis exhibits great variations in species’ distribution ranges, with most species in the derived lineages having a much wider range than those in the early-diverged lineages. Hybridization and WGD events have been suggested to occur in Causonis based on evidence of phylogenetic discordance. The genus, therefore, provides us with an opportunity to for explore different hybridization and polyploidization modes in lineages with contrasting species’ distribution ranges. However, the evolutionary history of Causonis incorporating potential hybridization and WGD events remains to be explored.

Results

With plastid and nuclear data from dense sampling, this study resolved the phylogenetic relationships within Causonis and revealed significant cyto-nuclear discordance. Nuclear gene tree conflicts were detected across the genus, especially in the japonica-corniculata clade, which were mainly attributed to gene flow. This study also inferred the allopolyploid origin of the core Causonis species, which promoted the accumulation of stress-related genes. Causonis was estimated to have originated in continental Asia in the early Eocene, and experienced glaciation in the early Oligocene, shortly after the divergence of the early-divergent lineages. The japonica-corniculata clade mainly diversified in the Miocene, followed by temperature declines that may have facilitated secondary contact. Species distribution modeling based on current climate change predicted that the widespread C. japonica tends to be more invasive, while the endemic C. ciliifera may be at risk of extinction.

Conclusions

This study presents Causonis, a genus with complex reticulate evolutionary history, as a model of how hybridization and WGD modes differ in lineages of contrasting species’ geographic ranges. It is important to consider specific evolutionary histories and genetic properties of the focal species within conservation strategies.
Independent wing reductions and losses among stick and leaf insects (Phasmatodea), supported by new Cretaceous fossils in amber
Authors: Yang Hongru , Engel Michael S. , Shih Chungkun , Song Fan , Zhao Yisheng , Ren Dong , Gao Taiping
Published: October 2023

Background

Phasmatodea (stick and leaf insects) play a central role on the debate regarding wing reduction and loss, and its wings are putative reacquisition from secondarily wingless ancestors based solely on extant species. A pivotal taxon in this respect is the species-poor Timematodea, consisting of approximately 21 wingless extant species, which form the sister group of all remaining winged or wingless stick and leaf insects, the Euphasmatodea.

Results

Herein, the new fossils of Timematodea from mid-Cretaceous Kachin amber are reported, with winged and wingless species co-occurring. The palaeogeographic distributions of all fossils of Holophasmatodea are summarized, showing their wide paleo-distributions. The phylogenetic analysis based on morphological characters confirms the earliest-diverging lineage of winged Breviala cretacea gen. et sp. nov. in Timematodea, and the possible relationships among all families of Holophasmatodea. These are critical for the reconstruction of patterns of wing evolution in early Phasmatodea.

Conclusions

The new fossils suggest that Timematodea once had wings, at least during the mid-Cretaceous. The palaeogeographic occurrences imply that Timematodea probably have been widely distributed since at least the Jurassic. The phylogenetic analysis with the ancestral-state reconstruction of wings indicates that the common ancestors of Holophasmatodea were winged, the reductions and losses of wings among Timematodea and Euphasmatodea have occurred independently since at least the Cretaceous, and the reduction or loss of the forewing earlier than the hind wings.
Mendelian randomization study confirms causal relationship between myopia and vitreous disorders
Authors: Xu Jiayu , Mo Ya
Published: October 2023

Purpose

This study aims to investigate the potential bidirectional causal relationship between myopia and vitreous disorders from a genetic perspective, as vitreous disorders have been found to be closely associated with myopia development.

Methods

To achieve this, a two-sample Mendelian randomization (MR) design was employed. The study utilized pooled statistics from independent genome-wide association studies. Myopia was chosen as the exposure factor, while five different vitreous disorders were considered as outcomes. The primary analytical method was the inverse variance weighting (IVW) method, supplemented by sensitivity analysis.

Results

The study yielded significant findings indicating a positive association between myopia and vitreous disorders. The genetic prediction of myopia consistently demonstrated a positive correlation with vitreous disorders, as evidenced by IVW (odds ratio [OR] = 18.387; P < 0.01), MR Egger (OR = 2784.954; P < 0.01), weighted median (OR = 30.284; P < 0.01), and weighted mode (OR = 57.381; P < 0.01). All sensitivity analyses further validated these associations. Furthermore, a significant association was observed between myopia and other unspecified vitreous body disorders (IVW: OR = 57.729; P < 0.01).

Conclusion

Studies mainly conducted in European populations have confirmed that myopia, extending beyond early high myopia, plays a crucial role in influencing vitreous disorders and that there is a unidirectional causal relationship between myopia and vitreous disorders. Additionally, a causal relationship was identified between myopia and other unspecified vitreous disordes. These findings introduce fresh perspectives for the clinical management of unspecified vitreous disorders and contribute to the understanding of the effect of myopia on vitreous disorders. Myopia prevention and treatment will aid in slowing down the process of vitreous liquefaction and subsequently decrease the incidence of malignant eye conditions.
Fibrosis and bone marrow: understanding causation and pathobiology
Authors: Ghosh Kanjaksha , Shome Durjoy K. , Kulkarni Bipin , Ghosh Malay K. , Ghosh Kinjalka
Published: October 2023

Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. The present review consolidates current understanding of marrow fibrosis. We searched PubMed without time restriction using key words: bone marrow and fibrosis as the main stem against the terms: growth factors, cytokines and chemokines, morphology, megakaryocytes and platelets, myeloproliferative disorders, myelodysplastic syndrome, collagen biosynthesis, mesenchymal stem cells, vitamins and minerals and hormones, and mechanism of tissue fibrosis. Tissue marrow fibrosis-related papers were short listed and analysed for the review. It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. Megakaryocytes and platelets are either directly involved or are important intermediaries in stimulating mesenchymal stem cells. MMPs, TIMPs, TGF-β, PDGRF, and basic FGF and CRCXL4 chemokines are involved in these processes. Genetic and epigenetic changes underlie many of these conditions.
Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine
Authors: Neves Vitor C. M. , Satie Okajima Luciana , Elbahtety Eyad , Joseph Susan , Daly James , Menon Athul , Fan Di , Volkyte Ayste , Mainas Giuseppe , Fung Kathy , Dhami Pawan , Pelegrine Andre A. , Sharpe Paul , Nibali Luigi , Ide Mark
Published: October 2023

Background

Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development.

Methods

The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors.

Results

We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients.

Conclusion

This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.
The association of moderate-to-vigorous physical activity and sedentary behaviour with abdominal aortic calcification
Authors: Sheng Chang , Huang Weihua , Wang Wei , Lin Guoqiang , Liao Mingmei , Yang Pu
Published: October 2023

Background and aims

The increasing prevalence of metabolic and cardiovascular diseases poses a significant challenge to global healthcare systems. Regular physical activity (PA) is recognized for its positive impact on cardiovascular risk factors. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA), sedentary behavior (SB), and abdominal aortic calcification (AAC) using data from the National Health and Nutrition Examination Survey (NHANES).

Methods

The study used data from NHANES participants aged 40 and above during the 2013–2014 cycle. AAC scores were assessed using the Kauppila scoring system, and MVPA and SB were self-reported. Sociodemographic variables were considered, and multivariable linear regression models were used to analyze associations between MVPA, SB, and AAC scores. Subgroup analyses were conducted based on age, sex, BMI, hypertension, and diabetes.

Results

The study included 2843 participants. AAC prevalence was higher in older age groups, smokers, and those with diabetes or hypertension. Lower socioeconomic status was associated with higher AAC prevalence. Individuals engaged in any level of MVPA exhibited lower AAC rates compared to inactive individuals. Not engaging in occupational MVPA (β = 0.46, 95% confidence interval = 0.24‒0.67, p < .001) and prolonged SB (β = 0.28, 95% confidence interval = 0.04‒0.52, p = .023) were associated with higher AAC scores. However, no significant associations were found for transportation and leisure time MVPA. Subgroup analysis revealed age and hypertension as effect modifiers in the MVPA-AAC relationship.

Conclusions

This study highlights the potential benefits of engaging in occupational MVPA and reducing SB in mitigating AAC scores, particularly among older individuals and those with hypertension.
The subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles
Authors: Chen Bang-Yao , Hong Si-Ying , Wang Han-Min , Shi Yi , Wang Peng , Wang Xiao-Juan , Jiang Qian-Yang , Yang Ke-Da , Chen Wei , Xu Xiao-Ling
Published: October 2023

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.
Osteonectin bidirectionally regulates osteoblast mineralization
Authors: Zhu Yun‑Sen , Mo Ting‑Ting , Jiang Chang , Zhang Jiang‑Nan
Published: October 2023

Objective

The aim of this study was to investigate whether Osteonectin/Secreted protein acidic and rich in cysteine (ON/SPARC) had a two-way dose-dependent regulatory effect on osteoblast mineralization and its molecular mechanism.

Methods

Initially, different concentrations of ON were added in osteoblasts, and the gene of bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN) and alkaline phosphatase (ALP) were detected using reverse‐transcription quantitative polymerase chain reaction (RT‐PCR). Secondly, based on the above results, the Optima and inhibitory concentration of ON for osteoblast mineralization were determined and regrouped, the Control group was also set up, and the gene detections of Collagen 1 (Col 1), Discoidin domain receptor 2 (DDR2) and p38 mitogen‑activated protein kinase were added using RT‐PCR. In the third stage of the experiment, osteoblasts were pretreated with 0.4Mm ethyl-3,4-dihydroxybenzoate (DHB) (a specific inhibitor of collagen synthesis) for 3 h before adding the optima SPARC, the gene and protein expressions of OCN, OPN, BSP, ALP, DDR2, ALP, Col 1, DDR2 and P38 were detected by RT‑qPCR and western blot analysis, and the mineralized nodules were observed by alizarin red staining.

Results

The results showed that the expression of OCN, OPN, BSP, ALP, DDR2, ALP, Col 1, DDR2 and P38 genes and proteins in osteoblasts were significantly enhanced by 1 ug/ml ON, 100 ug/ml ON or 1 ug/ml ON added with 3,4 DHB significantly inhibited the expressions of DDR2, P38 and the above-mentioned mineralization indexes, and significantly reduced the formation of mineralized nodules.

Conclusion

This study suggested that ON had a bidirectional dose-dependent regulatory effect on osteoblast mineralization, and the activation of P38 pathway by collagen binding to DDR2 was also an important molecular mechanism.
Correlation of retinal vascular characteristics with laboratory and ocular findings in Fabry disease: exploring ocular diagnostic biomarkers
Authors: Lindziute Migle , Kaufeld Jessica , Hufendiek Karsten , Volkmann Ingo , Brockmann Dorothee , Hosari Sami , Hohberger Bettina , Christian Mardin , Framme Carsten , Jan Tode , Hufendiek Katerina
Published: October 2023

Background

The goal of this study was to evaluate macular microvascular changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA) and to explore their correlation with laboratory and ocular findings.

Methods

A total of 76 eyes (38 patients) and 48 eyes of 24 healthy controls were enrolled in this prospective study. Vessel Area Density (VAD) and Foveal Avascular Zone (FAZ) area were calculated on 2.9 × 2.9 mm OCTA images scanned with the Heidelberg Spectralis II (Heidelberg, Germany). VAD was measured in three layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP). All scans were analyzed with the EA-Tool (Version 1.0), which was coded in MATLAB (The MathWorks Inc, R2017b). FAZ area was manually measured in full-thickness, SVP, ICP and DCP scans.

Results

Average VAD in SVP, ICP and DCP was higher in Fabry disease patients than in controls (49.4 ± 11.0 vs. 26.5 ± 6.2, 29.6 ± 7.4 vs. 20.2 ± 4.4, 32.3 ± 8.8 vs. 21.7 ± 5.1 respectively, p < 0.001). Patients with cornea verticillata (CV) had a higher VAD in ICP and DCP compared to patients without CV (p < 0.01). Patients with increased lysoGb3 concentration had a higher VAD in DCP when compared to patients with normal lysoGb3 concentration (p < 0.04). There was no difference in VAD in patients with and without vascular tortuosity. However, a significantly higher VAD was observed in patients with vascular tortuosity compared to controls (p < 0.03).

Conclusions

Increased lysoGb3 and VAD in DCP could be reliable biomarkers of disease activity. Cornea verticillata could be adopted as a predictive biomarker for VAD changes and disease progression. The combination of cornea verticillata and increased VAD may serve as a diagnostic biomarker for Fabry disease, however due to the discrepancies in VAD values in various studies, further research has to be done to address this claim.
Imaging of human papilloma virus (HPV) related oropharynx tumour: what we know to date
Authors: Bicci Eleonora , Calamandrei Leonardo , Mungai Francesco , Granata Vincenza , Fusco Roberta , De Muzio Federica , Bonasera Luigi , Miele Vittorio
Published: October 2023

The tumours of head and neck district are around 3% of all malignancies and squamous cell carcinoma is the most frequent histotype, with rapid increase during the last two decades because of the increment of the infection due to human papilloma virus (HPV). Even if the gold standard for the diagnosis is histological examination, including the detection of viral DNA and transcription products, imaging plays a fundamental role in the detection and staging of HPV + tumours, in order to assess the primary tumour, to establish the extent of disease and for follow-up. The main diagnostic tools are Computed Tomography (CT), Positron Emission Tomography-Computed Tomography (PET-CT) and Magnetic Resonance Imaging (MRI), but also Ultrasound (US) and the use of innovative techniques such as Radiomics have an important role. Aim of our review is to illustrate the main imaging features of HPV + tumours of the oropharynx, in US, CT and MRI imaging. In particular, we will outline the main limitations and strengths of the various imaging techniques, the main uses in the diagnosis, staging and follow-up of disease and the fundamental differential diagnoses of this type of tumour. Finally, we will focus on the innovative technique of texture analysis, which is increasingly gaining importance as a diagnostic tool in aid of the radiologist.
Regnase-1 downregulation promotes pancreatic cancer through myeloid-derived suppressor cell-mediated evasion of anticancer immunity
Authors: Okabe Junya , Kodama Takahiro , Sato Yu , Shigeno Satoshi , Matsumae Takayuki , Daiku Kazuma , Sato Katsuhiko , Yoshioka Teppei , Shigekawa Minoru , Higashiguchi Masaya , Kobayashi Shogo , Hikita Hayato , Tatsumi Tomohide , Okamoto Toru , Satoh Takashi , Eguchi Hidetoshi , Akira Shizuo , Takehara Tetsuo
Published: October 2023

Background

Pancreatitis is known to be an important risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the exact molecular mechanisms of how inflammation promotes PDAC are still not fully understood. Regnase-1, an endoribonuclease, regulates immune responses by degrading mRNAs of inflammation-related genes. Herein, we investigated the role of Regnase-1 in PDAC.

Methods

Clinical significance of intratumor Regnase-1 expression was evaluated by immunohistochemistry in 39 surgically-resected PDAC patients. The functional role of Regnase-1 was investigated by pancreas-specific Regnase-1 knockout mice and Kras-mutant Regnase-1 knockout mice. The mechanistic studies with gene silencing, RNA immunoprecipitation sequencing (RIP-seq) and immune cell reconstitution were performed in human/mouse PDAC cell lines and a syngeneic orthotopic tumor transplantation model of KrasG12D-mutant and Trp53-deficient PDAC cells.

Results

Regnase-1 expression was negatively correlated with the clinical outcomes and an independent predictor of poor relapse-free and overall survival in PDAC patients. Pancreas-specific Regnase-1 deletion in mice promoteed pancreatic cancer with PMN-MDSC infiltration and shortened their survival. A syngeneic orthotopic PDAC model exhibited that Regnase-1 downregulation accelerated tumor progression via recruitment of intratumor CD11b+ MDSCs. Mechanistically, Regnase-1 directly negatively regulated a variety of chemokines/cytokines important for MDSC recruitment and activation, including CXCL1, CXCL2, CSF2, and TGFβ, in pancreatic cancer cells. We subsequently showed that IL-1β-mediated Regnase-1 downregulation recruited MDSCs to tumor sites and promoted pancreatic cancer progression via mitigation of cytotoxic T lympohocytes-mediated antitumor immunity.

Conclusions

IL-1b-mediated Regnase-1 downregulation induces MDSCs and promotes pancreatic cancer through the evasion of anticancer immunity.
Severity of SARS-CoV-2 infection in a hospital population: a clinical comparison across age groups
Authors: Rosazza Chiara , Alagna Laura , Bandera Alessandra , Biffi Arianna , Ciciriello Fabiana , Gramegna Andrea , Lucidi Vincenzina , Marchisio Paola Giovanna , Medino Paola , Muscatiello Antonio , Uceda Renteria Sara , Colombo Carla
Published: October 2023

Background

Children tend to have milder forms of COVID-19 than adults, however post-acute complications have been observed also in the paediatric population. In this study, we compared COVID-19-related outcomes and long-term complications between paediatric and adult patients infected by SARS-CoV-2.

Methods

The study is based on individuals enrolled from October 2020 to June 2021 in the DECO COVID-19 multicentre prospective study supported by the Italian Ministry of Health (COVID-2020–12371781). We included individuals with RT-PCR -confirmed SARS-CoV-2 infection, who were evaluated in the emergency department and/or admitted to COVID-dedicated wards. The severity of SARS-CoV-2 infection was compared across age groups (children/adolescents aged < 18 years, young/middle-aged adults aged 18–64 years and older individuals) through the relative risk (RR) of severe COVID-19. Severity was defined by: 1) hospitalization due to COVID-19 and/or 2) need or supplemental oxygen therapy. RR and corresponding 95% confidence intervals were estimated using log-binomial models.

Results

The study included 154 individuals, 84 (54.5%) children/adolescents, 50 (32.5%) young/middle-aged adults and 20 (13%) older adults. Compared to young/middle-aged adults the risk of hospitalization was lower among paediatric patients (RR: 0.49, 95% CI: 0.32–0.75) and higher among older adults (RR: 1.52, 95% CI: 1.12–2.06). The RR of supplemental oxygen was 0.12 (95% CI: 0.05–0.30) among children/adolescents and 1.46 (95% CI: 0.97–2.19) among older adults. Three children developed multisystem inflammatory syndrome (MIS-C), none was admitted to intensive care unit or reported post-acute Covid-19 complications.

Conclusions

Our study confirms that COVID-19 is less severe in children. MIS-C is a rare yet severe complication of SARS-CoV-2 infection in children and its risk factors are presently unknown.
The diagnostic and therapeutic challenge of atrial flutter in children: a case report
Authors: De Nigris Angelica , Arenella Mattia , Di Nardo Giangiacomo , Marco Giovanni Maria Di , Mormile Annunziata , Lauretta Daria , De Simone Caterina , Pepe Angela , Cosimi Rosaria , Vastarella Rossella , Giannattasio Antonietta , Salomone Giovanni , Perrotta Silverio , Cioffi Speranza , Marzuillo Pierluigi , Tipo Vincenzo , Martemucci Luigi
Published: October 2023

Background

Palpitations represent a common cause for consultation in the pediatric Emergency Department (ED). Unlike adults, palpitations in children are less frequently dependent from the heart, recognizing other causes.

Case presentation

A 11-year-old male came to our pediatric ED for epigastric pain, vomiting and palpitations. During the previous 6 month the patient was affected by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus). Electrocardiogram (ECG) revealed supraventricular tachycardia. Therefore, adenosine was administered unsuccessfully. The administration of adenosine, however, allowed us to make diagnosis of atypical atrial flutter. Multiple attempts at both electrical cardioversion, transesophageal atrial overdrive, and drug monotherapy were unsuccessful in our patient. Consequently, a triple therapy with amiodarone, flecainide, and beta-blocker was gradually designed to control the arrhythmic pattern with the restoration of a left upper atrial rhythm. There was not any evidence of sinus rhythm in the patient clinical history.

Conclusions

The present study underlines the rarity of this type of dysrhythmia in childhood and the difficulties in diagnosis and management, above all in a patient who has never showed sinus rhythm. Raising awareness of all available treatment options is essential for a better management of dysrhythmia in children
The efficacy and ocular safety following aflibercept, conbercept, ranibizumab, bevacizumab, and laser for retinopathy of prematurity: a systematic review and meta-analysis
Authors: Chen Jing , Hao Qingfei , Zhang Jing , Du Yanna , Chen Haoming , Cheng Xiuyong
Published: October 2023

Background

Retinopathy of prematurity (ROP) is typically treated with laser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF). To the best of our knowledge, most systematic reviews have focused on comparing anti-VEGF against laser treatment while comparisons between different anti-VEGF agents are lacking. Thus, we conducted this meta-analysis to compare the efficacy and safety of different anti-VEGF agents or laser after primary ROP therapy.

Methods

We conducted a comprehensive search across multiple databases up to November 2022. We included studies that used anti-VEGF or laser for ROP with comparable cohorts.

Results

Overall, 44 studies were included in this meta-analysis. When comparing anti-VGEF with laser, we found that the anti-VEGF group had a significantly higher retreatment rate (RR = 1.56, 95%CI = [1.06, 2.31], p = 0.03), a longer time from treatment to retreatment (WMD = 5.99 weeks, 95%CI = [4.03, 7.95], p < 0.001), a lower retinal detachment rate (RR = 0.55, 95%CI = [0.30, 0.91], p = 0.02), higher spherical equivalent (WMD = 1.69D, 95%CI = [0.61, 2.77], p = 0.002), lower myopia rate (RR = 0.69, 95%CI = [0.50, 0.97], p = 0.03) and lower anisometropia rate (RR = 0.44, 95%CI = [0.29, 0.67], p = 0.0001). In comparisons between ranibizumab and bevacizumab, the intravitreal ranibizumab (IVR) group was associated with higher recurrence rate (RR = 2.02, 95%CI = [1.49, 2.73], p < 0.0001), higher retreatment rate (RR = 1.70, 95%CI = [1.17, 2.47], p = 0.0006), and lower high myopia rate (RR = 0.31, 95%CI = [0.12, 0.77], p = 0.01). Similarly, when compared to aflibercept and conbercept, the IVR cohort also demonstrated higher recurrence and retreatment rates. While no significant differences were observed in any of the variables included in the statistical analysis in the comparison between bevacizumab and aflibercept.

Conclusions

Anti-VEGF was associated with higher retreatment and lesser incidence of myopia as compared to laser. Laser therapy was linked to more complications like retinal detachment and myopia. Ranibizumab exhibited higher recurrence and retreatment rates compared to bevacizumab, aflibercept, and conbercept.
Lipidome of mammographic breast density in premenopausal women
Authors: Getz Kayla R. , Jeon Myung Sik , Luo Chongliang , Luo Jingqin , Toriola Adetunji T.
Published: October 2023

Background

High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.

Methods

Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log10 transformed, and lipid species were standardized. Linear coefficients of MBD were back-transformed and considered significant if the Bonferroni corrected p-value was < 0.05.

Results

Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m2, respectively. Fifty-six lipid species were significantly associated with VPD (52 inversely and 4 positively). The lipid species with positive associations were phosphatidylcholine (PC)(18:1/18:1), lysophosphatidylcholine (LPC)(18:1), lactosylceramide (LCER)(14:0), and phosphatidylinositol (PI)(18:1/18:1). VPD increased across quartiles of PI(18:1/18:1): (Q1 = 7.5%, Q2 = 7.7%, Q3 = 8.4%, Q4 = 9.4%, Bonferroni p-trend = 0.02). The lipid species that were inversely associated with VPD were mostly from the triacylglycerol (N = 43) and diacylglycerol (N = 7) sub-pathways. Lipid species explained some of the variation in VPD. The inclusion of lipid species increased the adjusted R2 from 0.45, for a model that includes known determinants of VPD, to 0.59.

Conclusions

We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.
A web-based educational therapy intervention associated with physical exercise to promote health in fibromyalgia in Brazil: the Amigos De Fibro (Fibro Friends) study protocol
Authors: Antunes Mateus Dias , da Rocha Loures Felipe Cayres Nogueira , de Souza Ingred Merllin Batista , Cruz Ariela Torres , de Oliveira Januário Priscila , Pinheiro Mara Maria Lisboa Santana , Schmitt Ana Carolina Basso , Frutos-Bernal Elisa , Martín-Nogueras Ana María , Marques Amélia Pasqual
Published: October 2023

Background

Health education is one of the main items to enable health promotion to patients with fibromyalgia. The objective of the study “Amigos de Fibro (Fibro Friends)” is to evaluate the impact of an educational intervention associated with physical exercise based on the web in promoting health and quality of life of patients with fibromyalgia in Brazil.

Methods

A study with a randomized controlled trial approach will be carried out. The sample will consist of 24 participants, divided into two groups, with 12 individuals each. The experimental group will participate in meetings with lectures, debates, conversation rounds and exercises by a multidisciplinary team. Physical exercises will also be performed in an online environment. On the other hand, the control group will receive an e-book of education and self-care. Primary outcomes will be quality of life. The secondary outcomes will be sociodemographic and health profile, pain intensity, sleep quality, self-care agency, usage and costs of health and social care services, viability of the program and program participation. In addition, a qualitative evaluation process will be carried out with the participants. After the intervention, the data of both groups will be collected again, as well as after 3, 6, and 12 months to verify the effect and the maintenance of the intervention.

Discussion

The results will provide data for studies to consider the use of this tool in the future by professionals working in the field of rheumatology.

Trial registration

The protocol was registered in the Brazilian Registry of Clinical Trials RBR-3rh759 (https://trialsearch.who.int/Trial2.aspx?TrialID=RBR-3rh759). Date of registration: 07/02/2020].
Translating medical device innovations to market - a Ugandan perspective
Authors: Matovu Brian , Baluka Jackline Winfred , Takuwa Mercy , Namuli Lucy Kevin , Mpaata Charles Norman , Mugaga Julius , Mulindwa Benedict , Nalwoga Racheal , Wolters Maria K , Ssekitoleko Robert Tamale
Published: October 2023

There is a disparity between low and middle-income countries (LMICs) and high-income countries (HICs) in translating medical device innovations to the market, affecting health care service delivery. Whereas medical technologies developed in HICs face substantial challenges in getting to the bedside, there are at least clear pathways in most of the major markets, such as the UK, the EU, and the USA. Much less is known about the challenges that innovators of medical technologies face in LMICs. The aim of this study was to map out current bottlenecks in medical device innovation in Uganda, a LMIC in Sub-Saharan East Africa.

A cross-sectional survey was carried out using a digital questionnaire. Twenty-one individuals completed the questionnaire, with the majority being medical device innovators (n = 12). Only one of these had undertaken all the innovation stages, up to clinical validation. Very few innovators had established companies, and/or acquired intellectual property. It is evident from similar studies that challenges in medical device translations are multidimensional, and hence interdisciplinary collaborations are key to accelerating translation processes, especially for LMICs.
Localized amyloidosis of the ureter: a case report
Authors: Aoki Shuntaro , Kawahara Takashi , Tajirika Hironao , Yasui Masato , Terao Hideyuki , Funahashi Makoto , Makiyama Kazuhide , Uemura Hiroji , Hayashi Hiroyuki , Ohta Junichi
Published: October 2023

Background

Amyloidosis is a collection of disorders characterized by the extracellular deposition of amyloid, a specialized fibrous protein, in diverse tissues, leading to functional impairments.

Case presentation

A 70-year old Asian-Japanese female was referred to our department for further examination of her left hydronephrosis come from lower ureteral obstruction. Contrast enhanced CT and retrograde pyelo-nephrography revealed left ureteral tumor. Though ureteroscropic biopsy did not show malignant pathological findings, ureteroscopic image suspected malignant disease, thus nephroureterectomy was performed. Pathological findings revealed localized ureteral amyloidosis. Whole body examination including gastro endoscopy and cardio ultrasonography could not reveal amyloidosis except ureter. She was free from recurrence 9 months postoperatively.

Conclusion

We herein report a rare case of localized ureteral amyloidosis.
Sex differences in the association between adipose insulin resistance and non-alcoholic fatty liver disease in Chinese adults
Authors: Wei Ying , Liu Jia , Wang Guang , Wang Ying
Published: October 2023

Background

Adipose insulin resistance (Adipo-IR) is associated with multiple metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The study aimed to evaluate sex differences in the association between Adipo-IR and NAFLD, and further investigated other potential modifiers.

Methods

This cross-sectional study enrolled adults without diabetes who underwent physical examinations in Beijing Chao-Yang Hospital. We calculated the Adipo-IR index as the product of the fasting insulin and free fatty acid concentration. We categorized Adipo-IR into four groups according to quartiles, using the first interquartile range (Q1) as the reference. Logistic regression was used stratified by the modifiers after adjustment for potential confounders.

Results

There were 5586 participants in the study, 49.8% (n = 2781) of whom were women and 30.4% (n = 1698) with NAFLD. There was a graded positive association between Adipo-IR and NAFLD, with sex (P = 0.01) and hyperlipidemia (P = 0.02) modifying this association. In the hyperlipidemic women, for one unit increase in log-Adipo-IR, the odds of having NAFLD increased by 385% after adjustment for potential confounders (OR = 4.85, 95%CI 3.54–6.73, P < 0.001). However, it turned out that the odds of having NAFLD increased by 131% (OR = 2.31, 95%CI 1.74–3.11, P < 0.001), 216% (OR = 3.16, 95%CI 2.56–3.93, P < 0.001), 181% (OR = 2.81, 95%CI 1.88–4.28, P < 0.001) in normolipidemic men, hyperlipidemic men, and normolipidemic women, respectively. Similarly, the ORs for the association between Adipo-IR and NAFLD in women with age ≥ 50 years were higher than ORs in women with age < 50 years.

Conclusions

The positive correlation between Adipo-IR and NAFLD was stronger in hyperlipidemic women, compared with normolipidemic or hyperlipidemic men, or normolipidemic women. The association also strengthened for women over 50 years. Treatment strategies targeting Adipo-IR to alleviate NAFLD may be of value, especially in hyperlipidemic women after menopause.
RETRACTED ARTICLE: Auto scheduling through distributed reinforcement learning in SDN based IoT environment
Authors: Wu Yuanyuan
Published: October 2023

The Internet of Things (IoT), which is built on software-defined networking (SDN), employs a paradigm known as channel reassignment. This paradigm has great potential for enhancing the communication capabilities of the network. The traffic loads may be scheduled more effectively with the help of an SDN controller, which allows for the transaction of matching channels via a single connection. The present techniques of channel reassignment, on the other hand, are plagued by problems with optimisation and cooperative multi-channel reassignment, which affect both traffic and routers. In this paper, we provide a framework for SDN–IoT in the cloud that permits multi-channel reassignment and traffic management simultaneously. The multi-channel reassignment based on traffic management is optimised via the use of a deep reinforcement learning technique, which was developed in this paper. We do an analysis of the performance metrics in order to optimise the throughput while simultaneously reducing the rate of packet loss and the amount of delay in the process. This is achieved by distributing the required traffic loads over the linked channels that make up a single connection.
Prioritization of e-traceability drivers in the agri-food supply chains
Authors: Krstić Mladen , Agnusdei Giulio Paolo , Tadić Snežana , Miglietta Pier Paolo
Published: October 2023

Electronic traceability (e-traceability) is a growing trend in the agri-food industry, offering improved transparency, accountability, and reduced risk of foodborne illnesses through the use of electronic systems to trace products throughout the entire supply chain. E-traceability drivers in the agri-food supply chain encompass diverse factors motivating companies to adopt electronic systems for product tracking, aiming to enhance visibility, minimize risk, ensure compliance, and promote safety, sustainability, and efficiency through clear and verifiable records of product origins, quality, and sustainability, building consumer trust and loyalty. By identifying the main drivers of e-traceability, this research aims to shed light on the factors that motivate companies to implement electronic systems for tracking and monitoring products. For solving this problem of multi-criteria decision-making (MCDM), this study proposes a hybrid MCDM model. The model combines “Factor Relationship” (FARE) and “Axial Distance-based Aggregated Measurement” (ADAM) methods in the fuzzy environment. The results indicate that the most important drivers are supply chain efficiency, technology development and sustainability. These drivers are critical and they significantly impact the successful implementation and adoption of e-traceability strategies in the agri-food sector.