bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing and validating measures of self-reported everyday and healthcare discrimination for Aboriginal and Torres Strait Islander adults
Authors: Thurber Katherine A. , Walker Jennie , Batterham Philip J. , Gee Gilbert C. , Chapman Jan , Priest Naomi , Cohen Rubijayne , Jones Roxanne , Richardson Alice , Calear Alison L. , Williams David R. , Lovett Raymond 
Published: January 2021

Abstract
Background
It is well established that racism is a fundamental contributor to poor health and inequities. There is consistent evidence of high exposure to discrimination among Aboriginal and Torres Strait Islander (Indigenous Australian) peoples, but impacts have not been fully quantified, in part due to limited measurement tools. We aim to validate instruments developed to measure interpersonal discrimination.

Methods
Instruments were discussed at five focus groups and with experts, and field tested in developing Mayi Kuwayu: The National Study of Aboriginal and Torres Strait Islander Wellbeing. Data from 7501 baseline survey participants were analysed. Acceptability was assessed according to extent of missingness, construct validity using exploratory and confirmatory factor analysis, and reliability using Cronbach’s alpha. Associations between each instrument and outcomes conceptually understood to be closely (community-level racism) or less closely (family wellbeing) related were quantified to test convergent and discriminant validity.

Results
An 8-item instrument captures experiences of discrimination in everyday life and a 4-item instrument experiences in healthcare, each followed by a global attribution item. Item missingness was 2.2–3.7%. Half (55.4%) of participants reported experiencing any everyday discrimination, with 65.7% attributing the discrimination to Indigeneity; healthcare discrimination figures were 34.1% and 51.1%. Items were consistent with two distinct instruments, differentiating respondents with varying experiences of discrimination. Scales demonstrated very good reliability and convergent and divergent validity.

Conclusion
These brief instruments demonstrate face validity and robust psychometric properties in measuring Aboriginal and Torres Strait Islander adults’ experiences of interpersonal discrimination in everyday life and in healthcare. They can be used to quantify population-level experiences of discrimination, and associated wellbeing consequences, and monitor change.
Clinical characteristics and predictors of mortality in young adults with severe COVID-19: a retrospective observational study
Authors: Lu Yanjiao , Huang Zhenli , Wang Meijia , Tang Kun , Wang Shanshan , Gao Pengfei , Xie Jungang , Wang Tao , Zhao Jianping 
Published: January 2021

Abstract
Background and objective
Little is yet known whether pathogenesis of COVID-19 is different between young and elder patients. Our study aimed to investigate the clinical characteristics and provide predictors of mortality for young adults with severe COVID-19.

Methods
A total of 77 young adults with confirmed severe COVID-19 were recruited retrospectively at Tongji Hospital. Clinical characteristics, laboratory findings, treatment and outcomes were obtained from electronic medical records. The prognostic effects of variables were analyzed using logistic regression model.

Results
In this retrospective cohort, non-survivors showed higher incidence of dyspnea and co-existing laboratory abnormalities, compared with young survivals in severe COVID-19. Multivariate logistic regression analysis showed that lymphopenia, elevated level of d-dimer, hypersensitive cardiac troponin I (hs-CTnI) and high sensitivity C-reactive protein (hs-CRP) were independent predictors of mortality in young adults with severe COVID-19. Further analysis showed that severely young adults with two or more factors abnormalities above would be more prone to death. The similar predictive effect of above four factors had been observed in all-age patients with severe COVID-19.

Conclusion
Lymphopenia, elevated level of d-dimer, hs-CTnI and hs-CRP predicted clinical outcomes of young adults with severe COVID-19.
Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1
Authors: Xing Shan , Tian Zhi , Zheng Wenying , Yang Wenjuan , Du Nan , Gu Yixue , Yin Jiang , Liu Hao , Jia Xiaoting , Huang Donglan , Liu Wanli , Deng Min 
Published: January 2021

Abstract
Background
MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC.

Methods
The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model.

Results
In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo.

Conclusions
Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.
Association between lipoprotein cholesterol and future cardiovascular disease and mortality in older adults: a Korean nationwide longitudinal study
Authors: Kim Seung Hee , Son Ki Young 
Published: January 2021

AbstractBackgroundDyslipidemia is considered an independent health risk factor of cardiovascular disease (CVD), a leading cause of mortality in older adults. Despite its importance, there have been few reports on the association between lipoprotein cholesterol and future CVD and cardiovascular (CV) mortality among elderly Asians aged ≥ 65 years. This study investigated the association between lipoprotein cholesterol and future CVD and CV mortality in an elderly Korean population using a large nationwide sample.MethodsFrom the cohort database of the Korean National Health Insurance Service, 62,604 adults aged ≥ 65 years (32,584 men and 30,020 women) were included. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were categorized by quartiles. Cox proportional hazard models and linear regression analyses were used to assess the association between the quartiles of lipoprotein cholesterol and future CV events or mortality.ResultsThe mean follow-up period was 3.3 years. The incidence rates of ischemic heart disease and ischemic brain disease were 0.97 and 0.61 per 1,000 person-years, respectively, and the mortality rates from these diseases were 0.22 and 0.34 per 1,000 person-years, respectively. In a completely adjusted model, high HDL-C and LDL-C levels were not associated with total CV events and CVD mortality. However, high LDL-C levels were significantly associated with a lower incidence of ischemic brain disease. Furthermore, diabetic patients with high LDL-C levels were more likely to have higher CV mortality, whereas non-smokers with high LDL-C levels were less likely to be at risk of CV events.ConclusionsNeither high LDL-C nor HDL-C levels were significantly associated with future CV mortality in older adults aged ≥ 65 years. High LDL-C levels do not seem to be a risk factor for CVD in elderly individuals, and further studies are required.
Contribution of sarcomere gene mutations to left atrial function in patients with hypertrophic cardiomyopathy
Authors: Chung Hyemoon , Kim Yoonjung , Park Chul Hwan , Kim In-Soo , Kim Jong-Youn , Min Pil-Ki , Yoon Young Won , Kim Tae Hoon , Lee Byoung Kwon , Hong Bum-Kee , Rim Se-Joong , Kwon Hyuck Moon , Lee Kyung-A , Choi Eui-Young 
Published: January 2021

Abstract
Background
Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling.

Methods
Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n = 30).

Results
Patients with HCM had lower late-diastolic mitral annular velocity (a’) and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n = 67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0 ± 18.5 vs. 44.2 ± 12.4%, p = 0.025). In patients without AF (n = 187), the PSM had lower a’ (6.9 ± 2.0 vs. 7.8 ± 1.9 cm/s, p = 0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a’ independent of E/e’, LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e’, s’, LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass.

Conclusions
PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM.
Hyaluronic acid modified covalent organic polymers for efficient targeted and oxygen-evolved phototherapy
Authors: Shu Fangpeng , Yang Taowei , Zhang Xuefeng , Chen Wenbin , Wu Kaihui , Luo Junqi , Zhou Xumin , Liu Guochang , Lu Jianming , Mao Xiangming 
Published: January 2021

AbstractThe integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.
Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer
Authors: Jing Boping , Gai Yongkang , Qian Ruijie , Liu Zhen , Zhu Ziyang , Gao Yu , Lan Xiaoli , An Rui 
Published: January 2021

Abstract
Background
Tumor cell-derived exosomes (TEx) have emerged as promising nanocarriers for drug delivery. Noninvasive multimodality imaging for tracing the in vivo trafficking of TEx may accelerate their clinical translation. In this study, we developed a TEx-based nanoprobe via hydrophobic insertion mechanism and evaluated its performance in dual single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer.

Results
TEx were successfully isolated from HCT116 supernatants, and their membrane vesicle structure was confirmed by TEM. The average hydrodynamic diameter and zeta potential of TEx were 110.87 ± 4.61 nm and –9.20 ± 0.41 mV, respectively. Confocal microscopy and flow cytometry findings confirmed the high tumor binding ability of TEx. The uptake rate of 99mTc-TEx-Cy7 by HCT116 cells increased over time, reaching 14.07 ± 1.31% at 6 h of co-incubation. NIRF and SPECT imaging indicated that the most appropriate imaging time was 18 h after the injection of 99mTc-TEx-Cy7 when the tumor uptake (1.46% ± 0.06% ID/g) and tumor-to-muscle ratio (8.22 ± 0.65) peaked. Compared with radiolabeled adipose stem cell derived exosomes (99mTc-AEx-Cy7), 99mTc-TEx-Cy7 exhibited a significantly higher tumor accumulation in tumor-bearing mice.

Conclusion
Hydrophobic insertion-based engineering of TEx may represent a promising approach to develop and label exosomes for use as nanoprobes in dual SPECT/NIRF imaging. Our findings confirmed that TEx has a higher tumor-targeting ability than AEx and highlight the potential usefulness of exosomes in biomedical applications.
Density of surface charge is a more predictive factor of the toxicity of cationic carbon nanoparticles than zeta potential
Authors: Weiss Maud , Fan Jiahui , Claudel Mickaël , Sonntag Thomas , Didier Pascal , Ronzani Carole , Lebeau Luc , Pons Françoise 
Published: January 2021

Abstract
Background
A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.6 to + 26.9 mV) but displaying an increasing surface charge density (electrokinetic charge, Qek from 0.23 to 4.39 µmol/g). An anionic and non-cytotoxic NP (NP1, ζ-potential = − 38.5 mV) was used as control.

Results
The 5 cationic NPs induced high (NP6 and NP5, Qek of 2.95 and 4.39 µmol/g, respectively), little (NP3 and NP4, Qek of 0.78 and 1.35 µmol/g, respectively) or no (NP2, Qek of 0.23 µmol/g) viability loss in THP-1-derived macrophages exposed for 24 h to escalating NP dose (3 to 200 µg/mL). A similar toxicity trend was observed in airway epithelial cells (A549 and Calu-3), with less viability loss than in THP-1 cells. NP3, NP5 and NP6 were taken up by THP-1 cells at 4 h, whereas NP1, NP2 and NP4 were not. Among the 6 NPs, only NP5 and NP6 with the highest surface charge density induced significant oxidative stress, IL-8 release, mitochondrial dysfunction and loss in lysosomal integrity in THP-1 cells. As well, in mice, NP5 and NP6 only induced airway inflammation. NP5 also increased allergen-induced immune response, airway inflammation and mucus production.

Conclusions
Thus, this study clearly reveals that the surface charge density of a cationic carbon NP rather than the absolute value of its ζ-potential is a relevant descriptor of its in vitro and in vivo toxicity.
Peer-assisted injection as a harm reduction measure in a supervised consumption service: a qualitative study of client experiences
Authors: Pijl Em , Oosterbroek Tracy , Motz Takara , Mason Erin , Hamilton Keltie 
Published: January 2021

Abstract
Background
Peer assistance is an emerging area of study in injection drug use. When Canada’s first supervised consumption site (SCS) opened in 2003 in Vancouver, Canada, clients were prohibited from injecting their peers; only recently has this practise been introduced as a harm reduction measure at these sites. In 2018, Health Canada granted federal exemption to allow peer-assisted injection at certain SCS sites, under the Controlled Drugs and Substances Act. Literature pertaining to peer-assisted injection addresses several topics: interpersonal relationships between the injection provider and recipient; the role of pragmatism; trust and expertise; and gender relations.

Methods
In this qualitative study, participants (n = 16) were recruited to be interviewed about their experiences in a peer-assisted injection program (PAIP) at one SCS regulated by Health Canada. Interview data were transcribed and thematically analyzed. Quantitative administrative data were used to provide context and to describe the study population, comprised of people in the PAIP (n = 248).

Results
PAIP clients made up 17.4% of all SCS clients. PAIP clients were more likely to be female and Indigenous. Injection providers expressed being moved by compassion to help others inject. While their desire to assist was pragmatic, they felt a significant burden of responsibility for the outcomes. Other prominent factors related to the injection provider-recipient relationship were social connection, trust, safety, social capital, and reciprocity. Participants also made suggestions for improving the PAIP which included adding more inhalation rooms so that if someone was unable to inject they could smoke in a safe place instead. Additionally, being required by law to divide drugs outside of the SCS, prior to preparing and using in the site, created unsafe conditions for clients.

Conclusions
Regular use of the SCS, and access to its resources, enabled participants to lower their risk through smoking and to practice lower-risk injections. At the federal level, there is considerable room to advocate for allowing clients to divide drugs safely within the SCS, and to increase capacity for safer alternatives such as inhalation.
Collaborative research and knowledge translation on road crashes in Burkina Faso: the police perspective 18 months on
Authors: Dagenais Christian , Proulx Michelle , Mc Sween-Cadieux Esther , Nikiema Aude , Bonnet Emmanuel , Ridde Valéry , Somé Paul-André 
Published: January 2021

AbstractIn this commentary, we present a follow-up of two articles published in 2017 and 2018 about road traffic crashes, which is an important public health issue in Africa and Burkina Faso. The first article reported on a research project, conducted in partnership with local actors involved in road safety, carried out in Ouagadougou in 2015. Its aim was to test the effectiveness, acceptability, and capacity of a surveillance system to assess the number of road traffic crashes and their consequences on the health of crash victims. Several knowledge translation activities were carried out to maximize its impact and were reported in the 2018 article published in HRPS: monthly reports presenting the research data, large-format printed maps distributed to the city’s police stations, and a deliberative workshop held at the end of the research project. The present commentary presents our efforts to deepen our understanding of the impacts of the knowledge translation strategy, based on follow-up interviews, 18 months after the workshop, with the heads of the road traffic crash units in Ouagadougou police stations (n = 5). Several benefits were reported by respondents. Their involvement in the process prompted them to broaden their knowledge of other ways of dealing with the issue of road crashes. This led them, sometimes with their colleagues, to intervene differently: more rapid response at collision sites, increased surveillance of dangerous intersections, user awareness-raising on the importance of the highway code, etc. However, sustaining these actions over the longer term has proven difficult. Several lessons were derived from this experience, regarding the importance of producing useful and locally applicable research data, of ensuring the acceptability of the technologies used for data collection, of using collaborative approaches in research and knowledge translation, of ensuring the visibility of actions undertaken by actors in the field, and of involving decision-makers in the research process to maximize its impacts.
Connecting the αα-hubs: same fold, disordered ligands, new functions
Authors: Staby Lasse , Bugge Katrine , Falbe-Hansen Rasmus Greve , Salladini Edoardo , Skriver Karen , Kragelund Birthe B. 
Published: January 2021

Abstract
Background
Signal fidelity depends on protein–protein interaction–‘hubs’ integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the αα-hubs were defined, which are small α-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators.

Methods
Comparative structural biology.

Results
We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the αα-hubs. The new member of the αα-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the αα-hubs. As a common trait, the αα-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk.

Conclusion
The inclusion of the HHD in the αα-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the αα-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.