bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objectively measuring the association between the built environment and physical activity: a systematic review and reporting framework
Authors: Pontin Francesca L. , Jenneson Victoria L. , Morris Michelle A. , Clarke Graham P. , Lomax Nik M. 
Published: September 2022

Abstract
Background
Objective measures of built environment and physical activity provide the opportunity to directly compare their relationship across different populations and spatial contexts. This systematic review synthesises the current body of knowledge and knowledge gaps around the impact of objectively measured built environment metrics on physical activity levels in adults (≥ 18 years). Additionally, this review aims to address the need for improved quality of methodological reporting to evaluate studies and improve inter-study comparability though the creation of a reporting framework.

Methods
A systematic search of the literature was conducted following the PRISMA guidelines. After abstract and full-text screening, 94 studies were included in the final review. Results were synthesised using an association matrix to show overall association between built environment and physical activity variables. Finally, the new PERFORM (’Physical and Environmental Reporting Framework for Objectively Recorded Measures’) checklist was created and applied to the included studies rating them on their reporting quality across four key areas: study design and characteristics, built environment exposures, physical activity metrics, and the association between built environment and physical activity.

Results
Studies came from 21 countries and ranged from two days to six years in duration. Accelerometers and using geographic information system (GIS) to define the spatial extent of exposure around a pre-defined geocoded location were the most popular tools to capture physical activity and built environment respectively. Ethnicity and socio-economic status of participants were generally poorly reported. Moderate-to-vigorous physical activity (MVPA) was the most common metric of physical activity used followed by walking. Commonly investigated elements of the built environment included walkability, access to parks and green space. Areas where there was a strong body of evidence for a positive or negative association between the built environment and physical activity were identified. The new PERFORM checklist was devised and poorly reported areas identified, included poor reporting of built environment data sources and poor justification of method choice.

Conclusions
This systematic review highlights key gaps in studies objectively measuring the built environment and physical activity both in terms of the breadth and quality of reporting. Broadening the variety measures of the built environment and physical activity across different demographic groups and spatial areas will grow the body and quality of evidence around built environment effect on activity behaviour. Whilst following the PERFORM reporting guidance will ensure the high quality, reproducibility, and comparability of future research.
Identification of CD8+ T cell subsets that normalize in early-treated people living with HIV receiving antiretroviral therapy
Authors: Perdomo-Celis Federico , Arcia-Anaya David , Alzate Juan Carlos , Velilla Paula A. , Díaz Francisco J. , Posada Maria Paulina , Rugeles María T. , Taborda Natalia A. 
Published: September 2022

AbstractBackgroundAlthough combined antiretroviral therapy (cART) has decreased the mortality associated with HIV infection, complete immune reconstitution is not achieved despite viral suppression. Alterations of CD8+T cells and some of their subpopulations, such as interleukin (IL)-17-producing cells, are evidenced in treated individuals and are associated with systemic inflammation and adverse disease outcomes. We sought to evaluate if different CD8+T cell subsets are differentially normalized during a clinical follow-up of people living with HIV (PLWH) receiving suppressive cART.MethodsWe explored the changes in the frequencies, activation/exhaustion phenotypes (HLA-DR, CD38, PD-1, and TIM-3), and function (total and HIV-specific cells expressing CD107a, perforin, granzyme B, interferon [IFN]-γ and IL-17) of CD8+T cells from early-treated PLWH receiving cART in a 1-year follow-up, using a multidimensional flow cytometry approach.ResultsDespite continuous cART-induced viral suppression and recovery of CD4+T cells, after a 1-year follow-up, the CD8+T cell counts, CD4:CD8 ratio, PD-1 expression, and IL-17 production by CD8+T cells exhibited incomplete normalization compared with seronegative controls. However, the proportion of CD8+T cells with an exhausted phenotype (co-expressing PD-1 andTIM-3), and cells co-expressing cytotoxic molecules (Perforin and Granzyme B), reached normalization.ConclusionsAlthough suppressive cART achieves normalization of CD4+T cell counts, only particular subsets of CD8+T cells are more rapidly normalized in PLWH receiving cART, which could be routinely used as biomarkers for therapy efficiency in these patients.
A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective
Authors: Siivola Kirsi M. , Burgum Michael J. , Suárez-Merino Blanca , Clift Martin J. D. , Doak Shareen H. , Catalán Julia 
Published: September 2022

AbstractThe number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.
Expression of immune checkpoint regulators, programmed death-ligand 1 (PD-L1/PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and indolaimine-2, 3-deoxygenase (IDO) in uterine mesenchymal tumors
Authors: Samiei Alireza , Gjertson David W. , Memarzadeh Sanaz , Konecny Gottfried E. , Moatamed Neda A. 
Published: September 2022

Abstract
Background
Immune checkpoints including programmed death-ligand 1/programmed death-1/ (PD-L1/PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and indolaimine-2, 3-deoxygenase (IDO) have recently emerged as effective candidates for treatment against a range of human malignancies. We have investigated their expression in the uterine mesenchymal tumors.

Methods
Sixty-eight mesenchymal tumors were categorized into 6 diagnostic groups. We assessed PD-L1, PD-1, CTLA-4, and IDO expression on paraffin embedded tissue blocks of the uterine tumors using the respective antibodies. Immunohistochemical (IHC) stains were classified as positive when the reactions were present in at least 1% of the cell membranes for PD-L1/PD-1 or in cytoplasm for CTLA-4 and IDO, regardless of intensity. Student’s t-test and McNemar’s chi-square tests were carried out to analyze the results.

Results
The mesenchymal neoplasms had expressed the immune checkpoints in the tumor and/or the lymphoid cells at the rate of 49% and 54% respectively. The tumor cells were positive in 10 (18%, PD-L1), 0 (0%, PD-1), 18 (32%, CTLA-4), and 13 (23%, IDO) cases while the infiltrating lymphoid cells were positive in 10 (18%, PD-L1), 23 (40%, PD-1), 18 (32%, CTLA-4), and 13 (23%, IDO) cases. Overall, comparison of paired tumor vs lymphoid cells resulted in p-values of ≤ 0.04.

Conclusions
Nearly 50% of the uterine tumors express at least one of the immune checkpoints in tumor and/or the infiltrating lymphoid cells. However, expression of the proteins in the two cellular components are mutually exclusive. Namely, when tumor cells express an immune checkpoint, the infiltrating lymphoid cells do not, and vice versa. Since the leiomyosarcomas are reportedly resistant to the immunotherapy when PD-L1 is expressed in the tumor cells, it can be posited that presence of the IHC positive lymphoid cells may be a better indicator of response to the treatment.
PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer
Authors: Ambur Sankaranarayanan Ramya , Florea Alexandru , Allekotte Susanne , Vogg Andreas T. J. , Maurer Jochen , Schäfer Laura , Bolm Carsten , Terhorst Steven , Classen Arno , Bauwens Matthias , Morgenroth Agnieszka , Mottaghy Felix M. 
Published: September 2022

Abstract
Background
Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCAmut). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125I.

Methods
TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm3, [123I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [125I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction.

Results
SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [125I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid.

Conclusion
Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [125I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.
Fintech application on banking stability using Big Data of an emerging economy
Authors: Yin Fang , Jiao Xiaomei , Zhou Jincheng , Yin Xiong , Ibeke Ebuka , Iwendi Marvellous GodsPraise , Biamba Cresantus 
Published: September 2022

AbstractThe rapid growth and development of financial technological advancement (Fintech) services and innovations have attracted the attention of scholars who are now on a quest to analyse their impact on the banking sector. This study conducts several kinds of analyses to measure the effect of the fintech era on the stability of the Chinese banking sector. It uses Big Data and performs Pearson correlation and regression analysis on the fintech era’s transition period to measure the impact of several explanatory variables— institutional regulation, government stability, bank credit to deposit ratio, and economic growth— on the outcome variables, which includes Nonperforming loans (NPLs) and its numerical measurement in relation to the mean score of the Big Data (Z-score). This study uses yearly Big Data from 1995–2018 and revealed that compared to the first wave of the fintech era, the second wave helped in the reduction of NPLs and the enhancement of financial stability in China. This study concludes that in the second wave of the fintech era, the explanatory variables mentioned above had a positive impact on NPLs and banking stability. This work helps comprehend fintech development in modern society and the importance of its disruptive forces in developing and developed countries.
Estimating the spatial correlation and convergence of China's healthcare resources allocation: evidence from the Yangtze River Delta Region
Authors: Shen Yuqing , Sun Zesheng 
Published: September 2022

Abstract
Background
China’s imbalanced allocation of healthcare resources mainly arises from urban–rural and intercity differences, the solution of which has been the goal of reforms during the past decades. Estimating the spatial correlation and convergence could help to understand the impact of China’s fast-evolving medical market and the latest healthcare reforms.

Methods
The entropy weight method was used to construct a healthcare resource supply index (HRS) by using data of 41cities in a cluster in the Yangtze River Delta (YRD) from 2007 to 2019. The Dagum Gini coefficient, kernel density estimation, Moran's I, and LISA cluster map were used to characterize the spatiotemporal evolution and agglomeration of healthcare resources, and then a spatial panel model was used to perform β convergence estimation by incorporating the spatial effect, city heterogeneity, and healthcare reforms.

Results
Healthcare resources supply in the YRD region increases significantly and converges rapidly. There is a significant spatial correlation and agglomeration between provinces and cities, and a significant spatial spillover effect is also found in β convergence. No evidence is found that the latest healthcare reforms have an impact on the balanced allocation and convergence of healthcare resources.

Conclusion
China’s long-term investment in past decades has yielded a more balanced allocation and intercity convergence of healthcare resources. However, the latest healthcare reforms do not contribute to the balanced allocation of healthcare resources from the supply-side, and demand-side analysis is needed in the future studies.
Adaptation and validation of a critical thinking scale to measure the 3D critical thinking ability of EFL readers
Authors: Mohammadi Moloud , Abbasian Gholam-Reza , Siyyari Masood 
Published: September 2022

AbstractThinking has always been an integral part of human life, and it can be said that whenever humanity has been thinking, it has been practicing a kind of criticizing the issues around. This is the concept of critical thinking that enhances the ability of individuals to identify problems and find solutions. Most previous research has focused on only one aspect of critical thinking that is critical thinking skills, while two other dimensions of criticality and critical pedagogy should have also been included. In order to assure of the validity of the instrument designed by Mohammadi et al. (Characterization and Development of Critically-thinker EFL Readers’ Reading Ability: Asynchronous Webbased Collaborative vs. Question-Answer-Relationship Instructional Approach, under review), it was first adapted and then SEM modeling was used. Examination of the results of factor analysis and modeling of SEM showed that the model satisfied the fit indices (χ2/df, CFI, TLI, RMSEA), and all the factor loads are greater than 0.4 which represent that the items are defined properly. This research suggested a SEM modeling of critical thinking skills, composed of six factors measured by twenty-two indices. The results of the PLS-SEM CFA represented that it is a valid structural model to measure a critical thinking of EFL readers at three levels.
A revitalisation of European farming and the promise of the biodynamic worldview
Authors: Wright Julia 
Published: September 2022

AbstractIn 2020 and amidst the upsurge in discourse around de-industrialisation, a consortium of sixteen indigenous leaders and organisations released a briefing statement that urged change amongst modern regenerative farming movements. Called ‘Whitewashed Hope’, the critique encouraged these movements to go deeper than simply taking indigenous practices out of context, but rather to encompass the worldviews they represent and in doing so to enable the cultural and relational changes needed for humanity’s collective healing. This paper takes a critical analysis approach to address the question of whether the critique of regenerative agriculture holds true for biodynamic agriculture in particular. This is explored using the hypothesis that there is no evidence of a synergistic relationship between the biodynamic worldview and the indigenous worldview as characterised in the document Whitewashed Hope. Drawing from the works of Rudolf Steiner as well as from other biodynamic texts, the paper uncovers synergies that exist between biodynamic and indigenous worldviews and explores the implications for regenerative farming systems. The aim of this paper is to instigate further debate and enquiry around the underexplored topic of how our worldviews impact our farming systems and of ways to develop an expanded worldview for more revitalised farming in the European context.
Graphical Abstract
Effective flow-through polishing strategies for knob-into-hole bispecific antibodies
Authors: Chen Serene W. , Hoi Kong Meng , Mahfut Farouq Bin , Yang Yuansheng , Zhang Wei 
Published: September 2022

AbstractBispecific antibodies (bsAbs), though possessing great therapeutic potential, are extremely challenging to obtain at high purity within a limited number of scalable downstream processing steps. Complementary to Protein A chromatography, polishing strategies play a critical role at removing the remaining high molecular weight (HMW) and low molecular weight (LMW) species, as well as host cell proteins (HCP) in order to achieve a final product of high purity. Here, we demonstrate using two knob-into-hole (KiH) bsAb constructs that two flow-through polishing steps utilising Capto Butyl ImpRes and Capto adhere resins, performed after an optimal Protein A affinity chromatography step can further reduce the HCP by 17- to 35-fold as well as HMW and LMW species with respect to monomer by ~ 4–6% and ~ 1%, respectively, to meet therapeutical requirement at 30–60 mg/mL-resin (R) load. This complete flow-through polishing strategy, guided by Design of Experiments (DoE), eliminates undesirable aggregation problems associated with the higher aggregation propensity of scFv containing bsAbs that may occur in the bind and elute mode, offering an improved ease of overall process operation without additional elution buffer preparation and consumption, thus aligning well with process intensification efforts. Overall, we demonstrate that through the employment of (1) Protein A chromatography step and (2) flow-through polishing steps, a final product containing < 1% HMW species, < 1% LMW species and < 100 ppm HCP can be obtained with an overall process recovery of 56–87%.Graphical Abstract
Development of a classifier for [18F]fluorodeoxyglucose extravasation severity using semi-quantitative readings from topically applied detectors
Authors: Perrin Steve , Kiser Jackson W. , Knowland Josh , Bowen Spencer L. 
Published: September 2022

Abstract
Background
Radiotracer extravasations, caused largely by faulty tracer injections, can occur in up to 23% of 18F-fluorodeoxyglucose (FDG) PET/CT scans and negatively impact radiological review and tracer quantification. Conventional radiological assessment of extravasation severity on PET has limited performance (e.g., extravasations frequently resolve before scanning) and practical drawbacks. In this study, we develop a new topical detector-based FDG extravasation severity classifier, calibrated from semi-quantitative PET measurements, and assess its performance on human subjects.

Methods
A retrospective study examined patients whose FDG injections had been monitored as part of their standard workup for PET/CT imaging. Topical uncollimated gamma ray detectors were applied proximal to the injection site and on the same location on the opposing arm, and readings were acquired continuously during radiotracer uptake. Patients were imaged with their arms in the PET field of view and total extravasation activity quantified from static PET images through a volume of interest approach. The image-derived activities were considered ground truth and used to calibrate and assess quantification of topical detector readings extrapolated to the start of PET imaging. The classifier utilizes the calibrated detector readings to produce four extravasation severity classes: none, minor, moderate, and severe. In a blinded study, a radiologist qualitatively labeled PET images for extravasation severity using the same classifications. The radiologist’s interpretations and topical detector classifications were compared to the ground truth PET results.

Results
Linear regression of log-transformed image-derived versus topical detector tracer extravasation activity estimates showed a strong correlation (R2 = 0.75). A total of 24 subject scans were cross-validated with the quantitatively based classifier through a leave-one-out methodology. For binary classification (none vs. extravasated), the topical detector classifier had the highest overall diagnostic performance for identifying extravasations. Specificity, sensitivity, accuracy, and positive predictive value were 100.0%, 80.0%, 95.8%, and 100.0%, respectively, for the topical detector classifier and 31.6%, 100.0%, 45.8%, and 27.8%, respectively, for the radiological analysis. The topical detector classifier, with an optimal detection threshold, produced a significantly higher Matthews correlation coefficient (MCC) than the radiological analysis (0.87 vs. 0.30).

Conclusions
The topical detector binary classifier, calibrated using quantitative static PET measurements, significantly improves extravasation detection compared to qualitative image analysis.