bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrosis and bone marrow: understanding causation and pathobiology
Authors: Ghosh Kanjaksha , Shome Durjoy K. , Kulkarni Bipin , Ghosh Malay K. , Ghosh Kinjalka 
Published: October 2023

AbstractBone 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

Abstract
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

Abstract
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

AbstractRecently, 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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.