bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is checklist an effective tool for teaching research students? A survey-based study
Authors: Makram Abdelrahman M , Wang Julia , Vaghela Gladson , Gala Dhir , Quan Nguyen Khoi , Duc Nguyen Tran Minh , Imoto Atsuko , Moji Kazuhiko , Huy Nguyen Tien 
Published: July 2022

Abstract
Background
Students face hardships in determining what are the main points that need more studying in every subject. Checklists are one of the ways that can help students identify the most important pieces of information. Accordingly, in this study, we aimed at examining the impact of using educational checklists on the learning process of postgraduate students at Nagasaki University, Japan.

Methods
Thirty-one Master's students, who finished a “how to write a research protocol” course were recruited by sending them an invitation email that had an attached link to a previously developed and tested questionnaire on the SurveyMonkey® platform. After signing the electronic informed consent, twenty-two participants (response rate = 71%) finished the survey. The data was analyzed using Microsoft Excel and expressed in the form of frequencies and percentages.

Results
More than half of the students declared that they know the checklist will be used in the course that we investigated. Only two students used checklists as a means of studying (9%). Twelve students (55%) confirmed that no other courses or lessons in the School of Tropical Medicine and Global Health (TMGH) use checklists. No students found the usage of checklists not easy or not practical to apply. Many students thought the length of the checklist was suitable and not too short (64%), although three students (14%) found it lengthy. Moreover, most students described the checklist as beyond good (86%) and they would recommend using a checklist for teaching other college students (73%).

Conclusion
Using checklists in education can facilitate the learning process, help in memorization, and deepen the concepts being studied. Further studies are required to examine the impact of checklists in teaching undergraduate students and students from other non-healthcare disciplines.
Application of artificial intelligence-based dual-modality analysis combining fundus photography and optical coherence tomography in diabetic retinopathy screening in a community hospital
Authors: Liu Rui , Li Qingchen , Xu Feiping , Wang Shasha , He Jie , Cao Yiting , Shi Fei , Chen Xinjian , Chen Jili 
Published: July 2022

Abstract
Background
To assess the feasibility and clinical utility of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and macular edema (ME) by combining fundus photos and optical coherence tomography (OCT) images in a community hospital.

Methods
Fundus photos and OCT images were taken for 600 diabetic patients in a community hospital. Ophthalmologists graded these fundus photos according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale as the ground truth. Two existing trained AI models were used to automatically classify the fundus images into DR grades according to ICDR, and to detect concomitant ME from OCT images, respectively. The criteria for referral were DR grades 2–4 and/or the presence of ME. The sensitivity and specificity of AI grading were evaluated. The number of referable DR cases confirmed by ophthalmologists and AI was calculated, respectively.

Results
DR was detected in 81 (13.5%) participants by ophthalmologists and in 94 (15.6%) by AI, and 45 (7.5%) and 53 (8.8%) participants were diagnosed with referable DR by ophthalmologists and by AI, respectively. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 91.67%, 96.92% and 0.944, respectively. For detecting referable DR, the sensitivity, specificity and AUC of AI were 97.78%, 98.38% and 0.981, respectively. ME was detected from OCT images in 49 (8.2%) participants by ophthalmologists and in 57 (9.5%) by AI, and the sensitivity, specificity and AUC of AI were 91.30%, 97.46% and 0.944, respectively. When combining fundus photos and OCT images, the number of referrals identified by ophthalmologists increased from 45 to 75 and from 53 to 85 by AI.

Conclusion
AI-based DR screening has high sensitivity and specificity and may feasibly improve the referral rate of community DR.
CircGPR137B/miR-4739/FTO feedback loop suppresses tumorigenesis and metastasis of hepatocellular carcinoma
Authors: Liu Lianyong , Gu Mingjun , Ma Junhua , Wang Ying , Li Miao , Wang Hui , Yin Xin , Li Xiangqi 
Published: July 2022

Abstract
Background
Emerging evidence indicates that circular RNAs (circRNAs) and m6A RNA methylation participate in the pathogenesis and metastasis of multiple malignancies including hepatocellular carcinoma (HCC). However, it remains undocumented how circRNAs form a feedback loop with the m6A modification contributing to HCC.

Methods
A novel hsa_circ_0017114 (circGPR137B) was identified from three pairs of primary HCC and adjacent normal tissues by circRNA expression profiling. The association of circGPR137B and miR-4739 with clinicopathological parameters and prognosis in patients with HCC was analyzed by RT-qPCR, fluorescence in situ hybridization and TCGA cohorts. The role of circGPR137B in HCC was estimated in vitro and in vivo. RT-qPCR, western blot, m6A dot blot, RIP, MeRIP and dual-luciferase reporter assays were used to validate the reciprocal regulation of the feedback loop among circGPR137B, miR-4739 and m6A demethylase FTO. Meanwhile, the expression, function and prognosis of FTO in HCC were investigated by RT-qPCR, western blot, TCGA and rescue experiments.

Results
We identified a new dramatically downregulated circGPR137B in HCC tissues, and found that downregulation of circGPR137B or upregulation of miR-4739 was associated with poor prognosis in patients with HCC. Ectopic expression of circGPR137B strikingly repressed the proliferation, colony formation and invasion, whereas knockdown of circGPR137B harbored the opposite effects. Moreover, restored expression of circGPR137B inhibited tumor growth and lung metastasis in vivo. Further investigations showed that circGPR137B, co-localized with miR-4739 in the cytoplasm, acted as a sponge for miR-4739 to upregulate its target FTO, which mediated m6A demethylation of circGPR137B and promoted its expression. Thus, a feedback loop comprising circGPR137B/miR-4739/FTO axis was formed. FTO suppressed cell growth and indicated favorable survival in patients with HCC.

Conclusion
Our results demonstrate that circGPR137B inhibits HCC tumorigenesis and metastasis through the circGPR137B/miR-4739/FTO feedback loop. This positive feedback mechanism executed by functional coupling between a circRNA sponge and an m6A modification event suggests a model for epigenetics.
Recent advances in smart nanoplatforms for tumor non-interventional embolization therapy
Authors: Dong Heng , Yang Dongliang , Hu Yanling , Song Xuejiao 
Published: July 2022

AbstractTumor embolization therapy has attracted great attention due to its high efficiency in inhibiting tumor growth by cutting off tumor nutrition and oxygen supply by the embolic agent. Although transcatheter arterial embolization (TAE) is the mainstream technique in the clinic, there are still some limitations to be considered, especially the existence of high risks and complications. Recently, nanomaterials have drawn wide attention in disease diagnosis, drug delivery, and new types of therapies, such as photothermal therapy and photodynamic therapy, owing to their unique optical, thermal, convertible and in vivo transport properties. Furthermore, the utilization of nanoplatforms in tumor non-interventional embolization therapy has attracted the attention of researchers. Herein, the recent advances in this area are summarized in this review, which revealed three different types of nanoparticle strategies: (1) nanoparticles with active targeting effects or stimuli responsiveness (ultrasound and photothermal) for the safe delivery and responsive release of thrombin; (2) tumor microenvironment (copper and phosphate, acidity and GSH/H2O2)-responsive nanoparticles for embolization therapy with high specificity; and (3) peptide-based nanoparticles with mimic functions and excellent biocompatibility for tumor embolization therapy. The benefits and limitations of each kind of nanoparticle in tumor non-interventional embolization therapy will be highlighted. Investigations of nanoplatforms are undoubtedly of great significance, and some advanced nanoplatform systems have arrived at a new height and show potential applications in practical applications.
Ablation of Siglec-E augments brain inflammation and ischemic injury
Authors: Li Lexiao , Chen Yu , Sluter Madison N. , Hou Ruida , Hao Jiukuan , Wu Yin , Chen Guo-Yun , Yu Ying , Jiang Jianxiong 
Published: July 2022

AbstractSialic acid immunoglobulin-like lectin E (Siglec-E) is a subtype of pattern recognition receptors found on the surface of myeloid cells and functions as a key immunosuppressive checkpoint molecule. The engagement between Siglec-E and the ligand α2,8-linked disialyl glycans activates the immunoreceptor tyrosine-based inhibitory motif (ITIM) in its intracellular domain, mitigating the potential risk of autoimmunity amid innate immune attacks on parasites, bacteria, and carcinoma. Recent studies suggest that Siglec-E is also expressed in the CNS, particularly microglia, the brain-resident immune cells. However, the functions of Siglec-E in brain inflammation and injuries under many neurological conditions largely remain elusive. In this study, we first revealed an anti-inflammatory role for Siglec-E in lipopolysaccharide (LPS)-triggered microglial activation. We then found that Siglec-E was induced within the brain by systemic treatment with LPS in mice in a dose-dependent manner, while its ablation exacerbated hippocampal reactive microgliosis in LPS-treated animals. The genetic deficiency of Siglec-E also aggravated oxygen–glucose deprivation (OGD)-induced neuronal death in mouse primary cortical cultures containing both neurons and glial cells. Moreover, Siglec-E expression in ipsilateral brain tissues was substantially induced following middle cerebral artery occlusion (MCAO). Lastly, the neurological deficits and brain infarcts were augmented in Siglec-E knockout mice after moderate MCAO when compared to wild-type animals. Collectively, our findings suggest that the endogenous inducible Siglec-E plays crucial anti-inflammatory and neuroprotective roles following ischemic stroke, and thus might underlie an intrinsic mechanism of resolution of inflammation and self-repair in the brain.
Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study
Authors: Ramasubramanian Ramya , Meier Helen C. S. , Vivek Sithara , Klopack Eric , Crimmins Eileen M. , Faul Jessica , Nikolich-Žugich Janko , Thyagarajan Bharat 
Published: July 2022

AbstractBackgroundCellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (TN) and increase in memory T-cells (TM). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously.MethodsWe developed two ARIP indicators based on well understood age-related changes in T cell distribution: TN/(TCM(Central Memory) + TEM(Effector Memory) + TEFF(Effector)) (referred as TN/TM) in CD4 + and CD8 + T-cells. We compared them with existing ARIP measures including CD4/CD8 ratio and CD8 + TN cells by evaluating associations with chronological age and the Klemera Doubal measure of biological age (measured in years) using linear regression, multimorbidity using multinomial logistic regression and two-year mortality using logistic regression.ResultsCD8 + TNand CD8 + TN/TMhad the strongest inverse association with chronological age (beta estimates: -3.41 and -3.61 respectively;p-value < 0.0001) after adjustment for sex, race/ethnicity and CMV status. CD4 + TN/TMand CD4 + TN had the strongest inverse association with biological age (β = -0.23;p = 0.003 and β = -0.24;p = 0.004 respectively) after adjustment for age, sex, race/ethnicity and CMV serostatus. CD4/CD8 ratio was not associated with chronological age or biological age. CD4 + TN/TMand CD4 + TNwas inversely associated with multimorbidity. For CD4 + TN/TM, people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63–0.86p = 0.0003) compared to those without any chronic conditions while those with 3 chronic conditions had an odds ratio of 0.75 (95% CI: 0.63–0.90;p = 0.003) after adjustment for age, sex, race/ethnicity, CMV serostatus, smoking, and BMI. The results for the CD4 + TNsubset were very similar to the associations seen with the CD4 + TN/TM. CD4 + TN/TMand CD4 + TNwere both associated with two-year mortality (OR = 0.80 (95% CI: 0.67–0.95;p = 0.01) and 0.81 (0.70–0.94;p = 0.01), respectively).ConclusionCD4 + TN/TMand CD4 + TNhad a stronger association with biological age, age-related morbidity and mortality compared to other ARIP measures. Future longitudinal studies are needed to evaluate the utility of the CD4 + subsets in predicting the risk of aging-related outcomes.
Grouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation: a case-study
Authors: Murphy Fiona , Jacobsen Nicklas Raun , Di Ianni Emilio , Johnston Helinor , Braakhuis Hedwig , Peijnenburg Willie , Oomen Agnes , Fernandes Teresa , Stone Vicki 
Published: July 2022

Abstract
Background
The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing.

Results
The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument.

Conclusion
This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of ‘similar’ MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.
How sports clubs decide to adopt an outdoor smoke-free policy: a qualitative study applying the Garbage Can Model
Authors: Garritsen Heike H. , Rozema Andrea D. , van de Goor Ien A. M. , Kunst Anton E. 
Published: July 2022

Abstract
Background
Outdoor smoke-free policies (SFPs) at sports clubs can contribute to protecting people from second-hand smoke (SHS). However, in absence of national legislation, it is uncertain whether and how sports clubs decide to adopt an SFP. The aim of this study was to explore the decision-making process at sports clubs in relation to the adoption of an outdoor SFP.

Methods
Semi-structured interviews were held with key stakeholders at 20 Dutch sports clubs (in field hockey, football, tennis, or korfball) with an outdoor SFP. Thematic analysis was applied, and themes were defined in line with the four streams of the Garbage Can Model (GCM).

Results
We identified four motivating factors for sports clubs to start the decision-making process: 1) SHS as a problem, 2) intolerance of smoking behavior, 3) advantages of an outdoor SFP, and 4) external pressure to become smoke-free. The decision-making process involved a variety of participants, but the board, influential club members, and smokers usually played major roles. Decisions were discussed during both formal and informal choice opportunities, but only made during formal choice opportunities. With regard to solutions, sports clubs adopted a partial or total outdoor SFP. In addition, sports clubs followed different strategies with regard to the decision-making process, which we classified along two dimensions: 1) autocratic vs. democratic and 2) fast vs. slow.

Conclusion
A number of factors motivated sports clubs to start the decision-making process. These factors were mainly linked to a strong non-smoking norm. Decision-making involved different participants, with a key role for the board, influential club members, and smokers. Governments and other external organizations may contribute to SFP adoption at sports clubs in several ways. They may advise clubs on strategies of decision-making and how to involve smokers in this process.
Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study
Authors: Ollila Henriikka , Pihlaja Riikka , Koskinen Sanna , Tuulio-Henriksson Annamari , Salmela Viljami , Tiainen Marjaana , Hokkanen Laura , Hästbacka Johanna 
Published: July 2022

Abstract
Background
Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU).

Methods
This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms.

Results
The groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037).

Conclusions
ICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions.
Trial registration number: ClinicalTrials.gov NCT04864938, retrospectively registered February 9, 2021
A prospective randomised controlled trial of mechanical axis with soft tissue release balancing vs functional alignment with bony resection balancing in total knee replacement—a study using Stryker Mako robotic arm-assisted technology
Authors: Young Simon W. , Zeng Nina , Tay Mei Lin , Fulker David , Esposito Christina , Carter Matthew , Bayan Ali , Farrington Bill , Van Rooyen Rupert , Walker Matthew 
Published: July 2022

Abstract
Background
Improving the functional outcome following total knee arthroplasty (TKA) by using different alignment techniques remains controversial. The surgical techniques and technologies used so far to obtain these alignments have all suffered from inaccuracies. The use of robotic technology to plan and execute the bony resection provides increased accuracy for these various alignment techniques and may determine which will deliver superior function. Functional alignment (FA) is a newer surgical technique that aims to position the prosthesis with respect to each patients’ specific bony anatomy whilst minimising disruption to the soft tissue envelope. This trial aims to compare the patient and surgical outcomes of FA to the current gold standard surgical technique, mechanical alignment (MA), under randomised and blinded conditions.

Methods
Patients with symptomatic knee osteoarthritis will be prospectively recruited. Following informed consent, 240 patients will be randomised to either a MA surgical technique (the control group) or a FA surgical technique (the intervention group) at a ratio of 4:1 using a random number generator. All patients will undergo computer tomography (CT) based robotic arm-assisted surgery to execute planned implant positioning and alignment with high levels of accuracy. The primary outcome is the forgotten joint score (FJS) at 2 years post-operation. Secondary outcome measures include patient reported outcome measures of post-operative rehabilitation, pain, function and satisfaction, as well as limb alignment, implant revisions and adverse events. Intention-to-treat and per-protocol population analysis will also be conducted. Standardisation of the surgical system and care pathways will minimise variation and assist in both patient and physiotherapist blinding. Ethical approval was obtained from the Northern B Health and Disability Ethics Committee (20/NTB/10).

Discussion
Currently, MA remains the gold standard in knee replacement due to proven outcomes and excellent long-term survivorship. There are many alternative alignment techniques in the literature, all with the goal of improving patient outcomes. This study is unique in that it leverages an advanced analytics tool to assist the surgeon in achieving balance. Both alignment techniques will be executed with high precision using the CT-based robotic arm-assisted surgery system which will minimise surgical variation. This trial design will help determine if FA delivers superior outcomes for patients.

Trial registration
Australia and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000009910. Registered on 9 January 2020. ClinicalTrials.gov, NCT04600583. Registered on 29 September 2020.