bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo
Authors: Zhang Zhe-Ao , Xin Xin , Liu Chao , Liu Yan-hong , Duan Hong-Xia , Qi Ling-ling , Zhang Ying-Ying , Zhao He-ming , Chen Li-Qing , Jin Ming-Ji , Gao Zhong-Gao , Huang Wei 
Published: December 2021

Abstract
Background
The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery.

Methods
PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied.

Results
The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona.

Conclusions
The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery.

Graphical Abstract
Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy
Authors: Huang Chunyu , Liu Zeming , Chen Mingzhu , Du Liang , Liu Chunping , Wang Shuntao , Zheng Yongfa , Liu Wei 
Published: December 2021

AbstractHigh doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.
Graphical Abstract
Preparation, toxicity reduction and radiation therapy application of gold nanorods
Authors: Xie Lina , Zhang Xujia , Chu Chengchao , Dong Yingqi , Zhang Tianzi , Li Xinyue , Liu Gang , Cai Wen , Han Suxia 
Published: December 2021

AbstractGold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy.Graphical Abstract
Development of a knowledge broker group to support evidence-informed policy: lessons learned from Myanmar
Authors: Paing Pyone Yadanar , Kyaw Zarni Lynn , Schojan Matthew , Traill Tom , Thura Si , Tin Nilar , Sein Than-Tun , Myint Hnin Hnin Tha , Bolton Paul , Lee Catherine 
Published: December 2021

Abstract
Background
Globally, policy-makers face challenges to using evidence in health decision-making, particularly lack of interaction between research and policy. Knowledge-brokering mechanisms can fill research–policy gaps and facilitate evidence-informed policy-making. In Myanmar, the need to promote evidence-informed policy is significant, and thus a mechanism was set up for this purpose. This paper discusses lessons learned from the development of the Knowledge Broker Group–Myanmar (KBG-M), supported by the Johns Hopkins Bloomberg School of Public Health’s Applied Mental Health Research Group (JHU) and Community Partners International (CPI).

Methods
Sixteen stakeholders were interviewed to explore challenges in formulating evidence-informed policy. Two workshops were held: the first to further understand the needs of policy-makers and discuss knowledge-brokering approaches, and the second to co-create the KBG-M structure and process. The KBG-M was then envisioned as an independent body, with former officials of the Ministry of Health and Sports (MoHS) and representatives from the nongovernmental sector actively engaging in the health sector, with an official collaboration with the MoHS.

Results
A development task force that served as an advisory committee was established. Then, steps were taken to establish the KBG-M and obtain official recognition from the MoHS. Finally, when the technical agreement with the MoHS was nearly complete, the process stopped because of the military coup on 1 February 2021, and is now on hold indefinitely.

Conclusions
Learning from this process may be helpful for future or current knowledge-brokering efforts, particularly in fragile, conflict-affected settings. Experienced and committed advisory committee members enhanced stakeholder relationships. Responsive coordination mechanisms allowed for adjustments to a changing bureaucratic landscape. Coordination with similar initiatives avoided overlap and identified areas needing technical support. Recommendations to continue the work of the KBG-M itself or similar platforms include the following: increase resilience to contextual changes by ensuring diverse partnerships, maintain advisory committee members experienced and influential in the policy-making process, ensure strong organizational and funding support for effective functioning and sustainability, have budget and timeline flexibility to allow sufficient time and resources for establishment, organize ongoing needs assessments to identify areas needing technical support and to develop responsive corrective approaches, and conduct information sharing and collaboration between stakeholders to ensure alignment.
Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study
Authors: Qu Heshuang , Sundberg Erik , Aulin Cecilia , Neog Manoj , Palmblad Karin , Horne Anna Carin , Granath Fredrik , Ek Alexandra , Melén Erik , Olsson Mia , Harris Helena Erlandsson 
Published: December 2021

Abstract
Background
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms.

Methods
Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA).

Results
The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA.

Conclusions
We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
Astrocytic C–X–C motif chemokine ligand-1 mediates β-amyloid-induced synaptotoxicity
Authors: Perez-Nievas Beatriz G. , Johnson Louisa , Beltran-Lobo Paula , Hughes Martina M. , Gammallieri Luciana , Tarsitano Francesca , Myszczynska Monika A. , Vazquez-Villasenor Irina , Jimenez-Sanchez Maria , Troakes Claire , Wharton Stephen B. , Ferraiuolo Laura , Noble Wendy 
Published: December 2021

Abstract
Background
Pathological interactions between β-amyloid (Aβ) and tau drive synapse loss and cognitive decline in Alzheimer’s disease (AD). Reactive astrocytes, displaying altered functions, are also a prominent feature of AD brain. This large and heterogeneous population of cells are increasingly recognised as contributing to early phases of disease. However, the contribution of astrocytes to Aβ-induced synaptotoxicity in AD is not well understood.

Methods
We stimulated mouse and human astrocytes with conditioned medium containing concentrations and species of human Aβ that mimic those in human AD brain. Medium from stimulated astrocytes was collected and immunodepleted of Aβ before being added to naïve rodent or human neuron cultures. A cytokine, identified in unbiased screens of stimulated astrocyte media and in postmortem human AD brain lysates was also applied to neurons, including those pre-treated with a chemokine receptor antagonist. Tau mislocalisation, synaptic markers and dendritic spine numbers were measured in cultured neurons and organotypic brain slice cultures.

Results
We found that conditioned medium from stimulated astrocytes induces exaggerated synaptotoxicity that is recapitulated following spiking of neuron culture medium with recombinant C–X–C motif chemokine ligand-1 (CXCL1), a chemokine upregulated in AD brain. Antagonism of neuronal C–X–C motif chemokine receptor 2 (CXCR2) prevented synaptotoxicity in response to CXCL1 and Aβ-stimulated astrocyte secretions.

Conclusions
Our data indicate that astrocytes exacerbate the synaptotoxic effects of Aβ via interactions of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting this chemokine–receptor pair as a novel target for therapeutic intervention in AD.
Efficacy of a technology-based client-centred training system in neurological rehabilitation: a randomised controlled trial
Authors: Knippenberg Els , Timmermans Annick , Coolen Jolijn , Neven Katrien , Hallet Peter , Lemmens Jolien , Spooren Annemie 
Published: December 2021

Abstract
Background
A client-centred task-oriented approach has advantages towards motivation and adherence to therapy in neurorehabilitation, but it is costly to integrate in practice. An intelligent Activity-based Client-centred Training (i-ACT), a low-cost Kinect-based system, was developed which integrates a client-centred and task-oriented approach. The objectives were (1) to investigate the effect of additional i-ACT training on functioning. And (2) to assess whether training with i-ACT resulted in more goal oriented training.

Methods
A single-blind randomised controlled trial was performed in 4 Belgian rehabilitation centres with persons with central nervous system deficits. Participants were randomly allocated through an independent website-based code generator using blocked randomisation (n = 4) to an intervention or control group. The intervention group received conventional care and additional training with i-ACT for 3 × 45 min/week during 6 weeks. The control group received solely conventional care. Functional ability and performance, quality of life (QoL), fatigue, trunk movement, and shoulder active range of motion (AROM) were assessed at baseline, after 3 weeks and 6 weeks of training, and 6 weeks after cessation of training. Data were analysed using non-parametric within and between group analysis.

Results
47 persons were randomised and 45 analysed. Both intervention (n = 25) and control (n = 22) group improved over time on functional ability and performance as measured by the Wolf Motor Function Test, Manual Ability Measure-36, and Canadian Occupational Performance Measure, but no major differences were found between the groups on these primary outcome measures. Regarding QoL, fatigue, trunk movement, and shoulder AROM, no significant between group differences were found. High adherence for i-ACT training was found (i.e. 97.92%) and no adverse events, linked to i-ACT, were reported. In the intervention group the amount of trained personal goals (88%) was much higher than in the control group (46%).

Conclusions
Although additional use of i-ACT did not have a statistically significant added value regarding functional outcome over conventional therapy, additional i-ACT training provides more individualised client-centred therapy, and adherence towards i-ACT training is high. A higher intensity of i-ACT training may increase therapy effects, and should be investigated in future research.
Trial registration: ClinicalTrials.gov Identifier NCT02982811. Registered 29 November 2016.
Survival prognostic and recurrence risk factors after single pulmonary metastasectomy
Authors: Forster Céline , Ojanguren Amaya , Perentes Jean Yannis , Zellweger Matthieu , Krueger Thorsten , Abdelnour-Berchtold Etienne , Gonzalez Michel 
Published: December 2021

Abstract
Background
Identification of the prognostic factors of recurrence and survival after single pulmonary metastasectomy (PM).

Methods
Retrospective analysis of all consecutive patients who underwent PM for a single lung metastasis between 2003 and 2018.

Results
A total of 162 patients with a median age of 64 years underwent single PM. Video-Assisted Thoracic Surgery (VATS) was performed in 83.9% of cases. Surgical resection was achieved by wedge in 73.5%, segmentectomy in 7.4%, lobectomy in 17.9% and pneumonectomy in 1.2% of cases. The median durations of hospital stay and of drainage were 4 days (IQR 3–7) and 1 day (IQR 1–2), respectively. During the follow-up (median 31 months; IQR 15–58), 93 patients (57.4%) presented recurrences and repeated PM could be realized in 35 patients (21.6%) achieved by VATS in 77.1%. Non-colorectal tumour (HR 1.84), age < 70 years (HR 1.77) and previous extra-thoracic metastases (HR 1.61) were identified as prognostic factors of recurrence. Overall survival at 5-year was estimated at 67%. Non-colorectal tumour (HR 2.40) and mediastinal lymph nodes involvement (HR 3.42) were significantly associated with an increased risk of death.

Conclusions
Despite high recurrence rates after PM, surgical resection shows low morbidity rate and acceptable long-term survival, thus should remain the standard treatment for single pulmonary metastases.
Trial registration: The Local Ethics Committee approved the study (No. 2019–02,474) and individual consent was waived.
Surgical techniques for aortic valve xenotransplantation
Authors: Kwon Jennie H. , Hill Morgan , Gerry Brielle , Kubalak Steven W. , Mohiuddin Muhammad , Kavarana Minoo N. , Rajab T. Konrad 
Published: December 2021

Abstract
Background
Heart valve replacement in neonates and infants is one of the remaining unsolved problems in cardiac surgery because conventional valve prostheses do not grow with the children. Similarly, heart valve replacement in children and young adults with contraindications to anticoagulation remains an unsolved problem because mechanical valves are thrombogenic and bioprosthetic valves are prone to early degeneration. Therefore, there is an urgent clinical need for growing heart valve replacements that are durable without the need for anticoagulation.

Methods
A human cadaver model was used to develop surgical techniques for aortic valve xenotransplantation.

Results
Aortic valve xenotransplantation is technically feasible. Subcoronary implantation of the valve avoids the need for a root replacement.

Conclusion
Aortic valve xenotransplantation is promising because the development of GTKO.hCD46.hTBM transgenic pigs has brought xenotransplantation within clinical reach.
A heart in a heart: a case report of spontaneous flail of bicuspid aortic valve
Authors: Mohammadi Khadije , Akrami Mahsa , Mirtajaddini Marzieh 
Published: December 2021

Abstract
Background
Aortic regurgitation is attributed to congenital and acquired abnormalities of the aortic valve or aortic valve supporting structures. The most common cause of aortic regurgitation is atherosclerotic degeneration of the valve, especially in the presence of a bicuspid aortic valve.

Case summary
A 25-year-old Persian man with no past medical history, developed dyspnea since 1 week before his first visit to the physician. He was an active person up to this time, and had no history of trauma or chest pain. Transthoracic echocardiography showed severe aortic regurgitation in the context of flail bicuspid aortic valve, with no evidence of endocarditis. Laboratory tests including blood cultures were negative for infection. The patient underwent aortic valve replacement and the diagnosis was confirmed at time of surgery.

Conclusion
This case represents noninfective and nontraumatic spontaneous flail of bicuspid aortic valve.
Bayesian inference of biomass growth characteristics for sugi (C. japonica) and hinoki (C. obtusa) forests in self-thinned and managed stands
Authors: Nicoulaud-Gouin Valérie , Gonze Marc-André , Hurtevent Pierre , Calmon Phillippe 
Published: December 2021

Abstract
Background
Forests are an important sink for atmospheric carbon and could release that carbon upon deforestation and degradation. Knowing stand biomass dynamic of evergreen forests has become necessary to improve current biomass production models. The different growth processes of managed forests compared to self-managed forests imply an adaptation of biomass prediction models.

Methods
In this paper we model through three models the biomass growth of two tree species (Japanese cedar, Japanese cypress) at stand level whether they are managed or not (self-thinning). One of them is named self-thinned model which uses a specific self-thinning parameter α and adapted to self-managed forests and an other model is named thinned model adapted to managed forests. The latter is compared to a Mitscherlich model. The self-thinned model takes into account the light competition between trees relying on easily observable parameters (e.g. stand density). A Bayesian inference was carried out to determine parameters values according to a large database collected.

Results
In managed forest, Bayesian inference results showed obviously a lack of identifiability of Mitscherlich model parameters and a strong evidence for the thinned model in comparison to Mitscherlich model. In self-thinning forest, the results of Bayesian inference are in accordance with the self-thinning 3/2 rule (α=1.4). Structural dependence between stand density and stand yield in self-thinned model allows to qualifying the expression of biological time as a function of physical time and better qualify growth and mortality rate. Relative mortality rate is 2.5 times more important than relative growth rate after about 40 years old. Stand density and stand yield can be expressed as function of biological time, showing that yield is independent of initial density.

Conclusions
This paper addressed stand biomass dynamic models of evergreen forests in order to improve biomass growth dynamic assessment at regional scale relying on easily observable parameters. These models can be used to dynamically estimate forest biomass and more generally estimate the carbon balance and could contribute to a better understanding of climate change factors.
Tuberculosis infection among youths in overcrowded university hostels in Kenya: a cross-sectional study
Authors: Maina Teresia , Willetts Annie , Ngari Moses , Osman Abdullahi 
Published: December 2021

Abstract
Background
Tuberculosis (TB) remains a top global health problem and its transmission rate among contacts is higher when they are cohabiting with a person who is sputum smear-positive. Our study aimed to describe the prevalence of TB among student contacts in the university and determine factors associated with TB transmission.

Methods
We performed a cross-sectional study with an active contact case finding approach among students receiving treatment at Kilifi County Hospital from January 2016 to December 2017. The study was conducted in a public university in Kilifi County, a rural area within the resource-limited context of Kenya. The study population included students attending the university and identified as sharing accommodation or off-campus hostels, or a close social contact to an index case. The index case was defined as a fellow university student diagnosed with TB at the Kilifi County Hospital during the study period. Contacts were traced and tested for TB using GeneXpert.

Results
Among the 57 eligible index students identified, 51 (89%) agreed to participate. A total of 156 student contacts were recruited, screened and provided a sputum sample. The prevalence of TB (GeneXpert test positive/clinical diagnosis) among all contacts was 8.3% (95% CI 4.5–14%). Among the 8.3% testing positive 3.2% (95% CI 1.0–7.3%) were positive for GeneXpert only. Sharing a bed with an index case was the only factor significantly associated with TB infection. No other demographic or clinical factor was associated with TB infection.

Conclusion
Our study identified a high level of TB transmission among university students who had contact with the index cases. The study justifies further research to explore the genetic sequence and magnitude of TB transmission among students in overcrowded university in resource limited contexts.