bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress, Problems, and Prospects: R2P 15 Years after the World Summit
Authors: Hunt Charles T. , Jacob Cecilia , Gallagher Adrian
Published: February 2021

This short article introduces the GR2P Forum reflecting on the Responsibility to Protect (R2P) doctrine 15 years after it was institutionalised at the international level through the World Summit Outcome Document. It contextualises the relevance of critical reflections on the R2P at its 15th anniversary and then lays out the aims and objectives of the Forum. It provides an overview of the different contributions, describing the perspectives of the authors and the key arguments they present.
The Ladder of Collaboration: Research on Joint Actions of Social Organizations against the COVID-19 Epidemic
Authors: Yang Bao , Xiao Lujun , Chen Kun
Published: February 2021

Joint actions of social organizations have been frequently seen and continuously optimized since the outbreak of the COVID-19. This article is aimed to identify and explore the typical forms and development trends of collaborative networks of social organizations. Given the case studies on joint actions of social organizations, it builds an analysis framework based on actor-network theory (ANT). Research findings are as follows. First, there are, among social organizations in their joint actions against COVID-19, “loose”, “vertical”, “decentralized” and other typical forms of collaborative network, with “decentralized” collaboration showing quite a high degree of initiative. Second, “complex needs” and “political opportunities” that emerge in times of emergency response, “social entrepreneurship” and “bridging connective social capital” that accumulate in normal times, among other factors, have combined to drive vertical collaborative networks towards decentralization. The above three forms of collaboration, each with irreplaceable functions, together comprise an ecosystem of joint actions of social organizations. This article calls the landscape of dynamic practice of joint actions of social organizations a “ladder of collaboration”.
Mapping Large-Scale Climate Variability to Hydrological Extremes: An Application of the Linear Inverse Model to Subseasonal Prediction
Authors: Tseng Kai-Chih , Johnson Nathaniel C. , Maloney Eric D. , Barnes Elizabeth A. , Kapnick Sarah B.
Published: February 2021

The excitation of the Pacific–North American (PNA) teleconnection pattern by the Madden–Julian oscillation (MJO) has been considered one of the most important predictability sources on subseasonal time scales over the extratropical Pacific and North America. However, until recently, the interactions between tropical heating and other extratropical modes and their relationships to subseasonal prediction have received comparatively little attention. In this study, a linear inverse model (LIM) is applied to examine the tropical–extratropical interactions. The LIM provides a means of calculating the response of a dynamical system to a small forcing by constructing a linear operator from the observed covariability statistics of the system. Given the linear assumptions, it is shown that the PNA is one of a few leading modes over the extratropical Pacific that can be strongly driven by tropical convection while other extratropical modes present at most a weak interaction with tropical convection. In the second part of this study, a two-step linear regression is introduced that leverages a LIM and large-scale climate variability to the prediction of hydrological extremes (e.g., atmospheric rivers) on subseasonal time scales. Consistent with the findings of the first part, most of the predictable signals on subseasonal time scales are determined by the dynamics of the MJO–PNA teleconnection while other extratropical modes are important only at the shortest forecast leads.
Climate Variability, Drought, and the Belief that High Gods Are Associated with Weather in Nonindustrial Societies
Authors: Ember Carol R. , Skoggard Ian , Felzer Benjamin , Pitek Emily , Jiang Mingkai
Published: February 2021

All societies have religious beliefs, but societies vary widely in the number and type of gods in which they believe as well as their ideas about what the gods do. In many societies, a god is thought to be responsible for weather events. In some of those societies, a god is thought to cause harm with weather and/or can choose to help, such as by bringing needed rain. In other societies, gods are not thought to be involved with weather. Using a worldwide, largely nonindustrial sample of 46 societies with high gods, this research explores whether certain climate patterns predict the belief that high gods are involved with weather. Our major expectation, largely supported, was that such beliefs would most likely be found in drier climates. Cold extremes and hot extremes have little or no relationship to the beliefs that gods are associated with weather. Since previous research by Skoggard et al. showed that greater resource stress predicted the association of high gods with weather, we also tested mediation path models to help us evaluate whether resource stress might be the mediator explaining the significant associations between drier climates and high god beliefs. The climate variables, particularly those pertaining to dryness, continue to have robust relationships to god beliefs when controlling on resource stress; at best, resource stress has only a partial mediating effect. We speculate that drought causes humans more anxiety than floods, which may result in the greater need to believe supernatural beings are not only responsible for weather but can help humans in times of need.
Indicators for the Measurement of Teachers’ Professional Identity across Asia and Africa: A Delphi Study
Authors: Samsudin Mohd Ali , Moen Melanie Carmen , Hai Pham Thi Thanh , Hagos Hailu Belay , Hidayat Arif , Ishida Yoko , Kusakabe Tatsuya , Ozawa Hiroaki , Ishak Nor Asniza , Malik Shaik Abdul , Ismail Bin Mohamed , Owoyemi Toyin Eunice , Anangisye William AL , Mgonda Nkanileka Loti , Asiimwe Joyce Ayikoru , Kyasanku Charles
Published: February 2021

The comprehensiveness of teacher professional identity (TPI) studies conducted by African and Asian researchers highlights the importance of valid TPI indicators across Africa and Asia. Questionnaire TPI indicators are important to obtain valid direct comparisons between teachers in Africa and Asia. The process of developing a questionnaire served as an avenue for researchers from Asian and African regions to learn about TPI pointers from each other. This study used the Delphi technique to achieve consensus on valid TPI indicators across African and Asian regions. Fourteen researchers from the Asia-Africa University Dialogue Network for Educational Development (AAD) were selected using purposive sampling. TPI in this study is defined as a multifaceted concept comprising contextual and personal factors that differ across national borders. The indicators in the questionnaire represented personal, social and institutional factors perceived by teachers and outlined in the literature. In the Delphi study process, the researchers used three rounds to validate the initial 40-item TPI questionnaire. Subsequent analysis of the results indicated high importance and consensus among experts. Owing to its standardized procedure, the TPI questionnaire makes it possible to collect and compare the TPI dimensions from the different socio-economic contexts in which teachers work in Africa and Asia. The findings of this study guide African and Asian researchers on the common understanding of TPI characteristics prevalent across African and Asian regions. Research protocols for fostering quality research toward addressing challenges faced by the teacher education sector in African and Asian countries is also implied.
The hack: What it is and why it matters to urban studies
Authors: Maalsen Sophia
Published: February 2021

This commentary advances the ‘hack’ as an urban concept. While the hack transcends existing literatures on the digital and informality, it is a distinctive concept and is being used systematically in new domains. I situate the hack conceptually, outline its empirical and methodological value and propose a framework to research the urban hack. Importantly, it is not just the technologies of hacking but the translation of computational logics to the urban that underpins the importance of the hack, as well as the critical need to set out a research agenda surrounding the hack within urban studies.
Re-Strategising Mission (and Development) Intervention into Africa to Avoid Corruption, the Prosperity Gospel and Missionary Ignorance
Authors: Harries Jim
Published: February 2021

The notion that Western ways are superior can be used to justify subsidising advocacy to the poor in Africa who might otherwise reject those ways out of ignorance. This ignores differences in culture that can trip up Western logic in Africa. When generosity is the reason to subsidise Western interventions, outside agents can be paid back in honour in ways not appropriate for Christians to accept. Perceived global inequalities used to convince donors to part with their money are impositions when those inequalities are not realised by recipients. When something inherently good, like the gospel, is routinely subsidised, some African people only value it when it comes with money. This disenfranchises poor evangelists. In order to overcome missionary ignorance, promotion of the prosperity gospel, and corruption associated with excessive foreign subsidies, this article advocates that vulnerable mission, namely, foreign intervention using local languages and resources, be permitted.
Revisiting rating scale development for rater-mediated language performance assessments: Modelling construct and contextual choices made by scale developers
Authors: Knoch Ute , Deygers Bart , Khamboonruang Apichat
Published: February 2021

Rating scale development in the field of language assessment is often considered in dichotomous ways: It is assumed to be guided either by expert intuition or by drawing on performance data. Even though quite a few authors have argued that rating scale development is rarely so easily classifiable, this dyadic view has dominated language testing research for over a decade. In this paper we refine the dominant model of rating scale development by drawing on a corpus of 36 studies identified in a systematic review. We present a model showing the different sources of scale construct in the corpus. In the discussion, we argue that rating scale designers, just like test developers more broadly, need to start by determining the purpose of the test, the relevant policies that guide test development and score use, and the intended score use when considering the design choices available to them. These include considering the impact of such sources on the generalizability of the scores, the precision of the post-test predictions that can be made about test takers’ future performances and scoring reliability. The most important contributions of the model are that it gives rating scale developers a framework to consider prior to starting scale development and validation activities.
Coping with Standards: Integrating Art and Safety into the Design of a Creative Playground
Authors: Lundman Riina
Published: February 2021

Technical safety standards have a strong yet controversial impact on the design of current playgrounds. This article studies the process of making a unique art-playground under the strict safety requirements. Building on the case study of a participatory design project between artists and children in Turku, Finland, this paper discusses the many legal and technical ambiguities regarding the playground standardization and investigates artists’ experiences of implementing standards in their work. The article shows that despite the controversies, it is possible to make playgrounds that comply with the standards, respect children’s desires, and are original and creative in their appearance.
Rosa Luxemburg in Mexico: On the Return of Primitive Accumulation
Authors: Whitener Brian
Published: February 2021

Perhaps no concept has shaped discussions of capitalism and its contemporary transformations more than that of ongoing primitive accumulation. This paper examines, accounts for, and unpacks how primitive accumulation came, within a certain genre of conversations, to be so central. While there have been prior critiques of its usage, notably by Robert Brenner, few have returned to the source of the modern framing of the concept, Rosa Luxemburg. Through a discussion of David Harvey’s updating of primitive accumulation as accumulation by dispossession, I return to Luxemburg in order to extract two methodological principles from her work: follow the production of aspects of accumulation and think their organic link and track violence. I then deploy these methodological principles in a discussion of certain critical processes of accumulation in contemporary Mexico to demonstrate the spatialized “organic link” of Luxemburg and Harvey has been violently reconstituted.
Influence of hydraulic versus pneumatic working fluids on quasi-static force response of fluidic artificial muscles
Authors: Chambers Jonathan M , Wereley Norman M
Published: February 2021

There is currently an increased interest in extending the application of McKibben actuators beyond gaseous environments and working fluids. Extensive efforts have already established force response models for pneumatically driven McKibben actuators that are independent of working fluid material properties, however, the model’s independence to working fluid choice has yet to be validated with empirical evidence. This paper experimentally investigates the effect of working fluid type on the quasi-static pressure dependent force-contraction response of McKibben actuators. Using either air or water as the working fluid, characteristic isobaric force-contraction response curves are compared for both large and small-scale McKibben actuators. To ensure truly isobaric force-contraction characterizations, hydraulic and pneumatic pressure systems were developed to provide precise and accurate control of pressure. Experimental testing proved using air or water as the working fluid resulted in nearly identical isobaric force-contraction response curves, demonstrating that McKibben actuator’s quasi-static force response is independent of working fluid choice. This study establishes that the applicability of existing force response models for pneumatic McKibben actuators can be extended to any practical liquids or gases.
A review on swelling theories of pH-sensitive hydrogels
Authors: Bayat Mohammad Reza , Baghani Mostafa
Published: February 2021

The pH-sensitive hydrogels are a unique class of three-dimensional hydrophilic polymers containing ionic pendant groups on their polymeric network. In response to the external pH variation, these materials span the volume of an aqueous/biological solution and swell without dissolution. Nowadays, the pH-sensitive hydrogels have attracted the growing interest of many researchers in various fields of researches such as drug delivery, tissue engineering, soft actuators, etc. which makes the simulation of their behavior crucial for optimum utilization. The essential prerequisite for the simulation of these materials is the swelling theory. In this article, we present a review of the fundamental phenomena in swelling theories of the pH-sensitive hydrogels. We also classify the swelling theories into two groups including the monophasic and multiphasic theories. Then, we briefly examine the most highlighted swelling theories in each group. The experimental data is essential for material parameters estimation as well as verification of the constitutive equations. Thus, we introduce and discuss the most highlighted experiments on the swelling and deswelling behavior of the pH-sensitive hydrogels as well.
Tiny but Mighty: Collision Tumor of a Superficial Adenocarcinoma Arising From a Tubulovillous Adenoma with Associated Low-Grade Follicular Lymphoma
Authors: Lin Yee Sing , Hamilton Auerilius E. R. , Henderson Christopher , Farzin Mahtab
Published: February 2021

Collision tumors are rare and there have only been a few previously described cases between an intestinal adenoma and a lymphoma. We report the first case of a 74-year-old woman who on investigation for iron deficiency had a tubulovillous adenoma with underlying follicular lymphoma. The atypical lymphoid proliferation showed immunohistochemical positivity for cluster of differentiation 20 (CD20), B-cell lymphoma 2 (BCL2), and B-cell lymphoma 6 (BCL6). Subsequent right hemicolectomy showed a superficially invasive adenocarcinoma.
The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review
Authors: Chen Ke , Wang Xiao , Yang Liu , Chen Zheling
Published: February 2021

Background:

Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy.

Method:

Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy).

Results:

After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002).

Conclusion:

For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.
Different Routes to University: Exploring Intersectional and Multi-Dimensional Social Mobility Under A Comparative Approach in Chile
Authors: Sepúlveda Denisse , Lizama-Loyola Andrea
Published: February 2021

The article aims to cover a gap in research, including an ethnic dimension to explore the relationship between people’s trajectories and their experiences at university. Drawing on a retrospective life-story approach, the article compares how 55 respondents of different social origins recount both their routes to university and their experiences at university. By adopting an intersectional lens of analysis, we argue that differential experiences at university affect people’s trajectories of social mobility. Data from two qualitative studies are analysed in this article to explore how class and ethnic background, but also people’s location in urban or rural areas and other aspects of their family situation, affected their educational routes to earning a university place. We argue for the subjective experience of social mobility as a process of achievement, but one fraught with numerous obstacles and challenges. This article shows that respondents from working-class social backgrounds encounter different barriers because of the lack of socioeconomic resources, previous educational disadvantages, class/ethnic discrimination, and family cultural background. Meanwhile, respondents from middle-class and upper-class backgrounds have to face different issues related to their families’ expectations of maintaining their social status. Based on those findings, we suggest that research on social mobility needs to consider multiple and intersectional dimensions that frame an individual’s life trajectories, instead of focusing on movements between fixed educational or occupational positions.
Ontological diversity in urban self-organization: Complexity, critical realism and post-structuralism
Authors: Boonstra Beitske , Rauws Ward
Published: February 2021

As urban self-organization grows into a key concept in spatial planning—explaining spontaneous spatial transformations—the understandings and applications of the concept divert. This article turns to the ontological dimension of urban self-organization and scrutinizes how a critical realist and a post-structuralist ontology inspire theoretical practices, analytical tendencies, empirical readings, and subsequent planning interventions in relation to urban self-organization. This is illustrated with an example of the self-organized regeneration of a deprived street in Rotterdam, the Netherlands. With this contribution, we aim to create ontological self-awareness among planning scholars in studying urban self-organization and invite them to reflect on how their positions complement, deviate, and potentially challenge or inspire those of others. We argue that by clarifying ontological diversity in urban self-organization, theoretical practices and complexity-informed planning interventions can be further deepened and enriched.
Outcomes of Management of Recurrent Dupuytren Contracture: A Systematic Review and Meta-analysis
Authors: Wong Chloe R. , Huynh Minh N. Q. , Fageeh Rotana , McRae Matthew C.
Published: February 2021

Background:

With numerous treatment modalities available, it is unclear whether the treatment of recurrent Dupuytren disease is as effective as its initial treatment. We aimed to investigate the outcomes of management of recurrent Dupuytren contracture.

Methods:

Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, Embase, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials were searched from their inception to April 2020. Studies of patients aged above 18 years undergoing treatment for recurrent Dupuytren contractures were included. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment. The study was registered with Open Science Foundation.

Results:

A systematic review identified 12 studies: 311 patients with 224 affected digits—index (n = 5; 2.2%), long (n = 17; 7.6%), ring (n = 57; 25.4%), small (n = 112; 50%), and unspecified (n = 33; 14.7%); of these, there were 76 metacarpophalangeal joints (MCPJ; 45.5%), 90 proximal phalangeal joints (PIPJ; 53.9%), and 1 distal interphalangeal joint (0.6%). Previous treatment included the following: percutaneous needle aponeurotomy (n = 103 of 311 patients; 33.1%), collagenase clostridium histolyticum-injection (CCH; n = 75 of 311; 24.1%), limited fasciectomy (LF) ± skin graft (n = 83 of 311; 26.7%), fasciotomy (n = 1 of 311; 0.3%), and unspecified (n = 64 of 311; 20.6%). Recurrence was treated by percutaneous needle aponeurotomy (n = 68 of 311 patients; 21.9%); CCH injection (n = 53 of 311; 17.0%); aponeurotomy or dermofasciectomy or LF (n = 176 of 311; 56.6%); ray/digit amputation (n = 8 of 311; 2.6%); and PIPJ arthrodesis (n = 6 of 293; 2.0%). Range of motion was improved by 23.31° (95% confidence interval [CI] = 13.13°-33.50°; I2 = 67%; P = .05) and 15.49° (95% CI = 2.67°-28.31°; I2 = 76%; P = .01) for MCPJ and PIPJ, respectively.

Conclusions:

There is low level of evidence that both surgical and nonsurgical treatments provide clinically important improvements for recurrent Dupuytren contracture.
Qualitative Evidence Synthesis: Where Are We at?
Authors: Flemming Kate , Noyes Jane
Published: February 2021

Qualitative evidence syntheses (QES) have increased in prominence and profile over the last decade as a discrete set of methodologies to undertake systematic reviews of primary qualitative research in health and social care and in education. The findings from a qualitative evidence synthesis can enable a richer interpretation of a particular phenomenon, set of circumstances, or experiences than single primary qualitative research studies can achieve. Qualitative evidence synthesis methods were developed in response to an increasing demand from health and social professionals, policy makers, guideline developers and educationalists for review evidence that goes beyond “what works” afforded by systematic reviews of effectiveness. The increasing interest in the synthesis of qualitative research has led to methodological developments documented across a plethora of texts and journal articles. This “State of the Method” paper aims to bring together these methodological developments in one place, contextualizing advances in methods with exemplars to support readers in making choices in approach to a synthesis and aid understanding. The paper clarifies what a “qualitative evidence synthesis” is and explores its role, purpose and development. It details the kind of questions a QES can explore, the processes associated with a QES, including the methods for synthesis. The rational and methods for integrating a QES with systematic reviews of effectiveness are also detailed. Finally approaches reporting and recognition of what a “good” or rigorous QES look like are provided.
Reliability and validity of the Hypoxico Everest Summit II altitude generator
Authors: Harwood B. , Wright J. , Burnet S.
Published: February 2021

The Hypoxico Everest Summit II Altitude Generator produces normobaric hypoxic conditions, which are commonly used in altitude acclimation. Despite being used routinely within applied sport science, this system is yet to be independently validated. Thus, the aim of this study was to explore within- and between-day inter- and intra-machine reliability and validity. Two Hypoxico Everest Summit II Altitude Generators were investigated for six altitude settings in a randomised order (0.5, 3.0, 5.5, 8.0, 10.5, 12.0). Following institutional ethics approval, Hypoxico generated air was sequentially pumped into three Douglas bags, each with a 1-min collection period. Samples were collected on eight occasions, measuring inter- and intra-machine reliability, both within-day (9 AM–2 PM) and between-day (48-h) with samples analysed to determine FiO2 (%) and volume (L·min−1). Coefficient of variation (CV) was calculated for FiO2 and volume for each altitude setting. Mean CV for FiO2 did not exceed 0.42% within-day, 0.49% between-day and 0.81% inter-machine. Volume mean CV did not exceed 0.85% within-day, 0.91% between-day and 1.17% inter-machine. One-sampled t-tests were conducted comparing Hypoxico reference values with collected samples using equivalent FiO2 for each altitude setting with a Bonferroni corrected significance set at p < 0.004. Settings 3.0, 5.5, 8.0, 10.5 and 12.0 all produced significantly different ( p < 0.001) FiO2 concentrations than the reference values stated (−0.51, −0.97, −0.72, +0.41 and +0.40%, respectively). Altitude setting and 1-min volume had an inverse relationship. All settings produced a significantly lower ( p < 0.001) volume by 21.80 to 35.40 L·min−1 as compared to the company’s claim of 126.6 L·min−1. The Hypoxico Everest Summit II produced a reliable and consistent air feed; however, the manufacturer’s reference values demonstrated poor agreement with machine produced FiO2 and volume. Therefore, it is recommended that athletes, practitioners and researchers self-validate the altitude generator post-warm-up using an accurate oxygen sensor for accuracy and safety purposes.
Shoulder Pain Diagnosis, Treatment and Referral Guidelines for Primary, Community and Intermediate Care
Authors: Rees Jonathan L , Kulkarni Rohit , Rangan Amar , Jaggi Anju , Brownson Peter , Thomas Michael , Clark David , Jenkins Paul , Candal-Couto Jaime , Shahane Shantanu , Peach Christopher , Falworth Mark , Drew Stephen , Trusler Julia , Turner Phillip , Molloy Aoife
Published: February 2021

[Formula: see text][Formula: see text]

These care pathway guidelines for the shoulder have been written in collaboration with the NHS Evidence Based Interventions (EBI) programme. The EBI programme is a partnership between the Academy of Medical Royal Colleges, NHS Clinical Commissioners, the National Institute for Health and Care Excellence, as well as NHS England and Improvement
Rho AI – Leveraging artificial intelligence to address climate change: Financing, implementation and ethics
Authors: Fischer Isabel , Beswick Claire , Newell Sue
Published: February 2021

The case focusses on Rho AI, a data science firm, and its attempt to leverage artificial intelligence to encourage environmental, social and governance investments to limit the impact of climate change. Rho AI’s proposed open-source artificial intelligence tool integrates automated web scraping technology and machine learning with natural language processing. The aim of the tool is to enable investors to evaluate the climate impact of companies and to use this evaluation as a basis for making investments in companies. The case study allows for students to gain an insight into some of the strategic choices that need to be considered when developing an artificial intelligence–based tool. Students will be able to explore the role of ethics in decision-making related to artificial intelligence, while familiarising themselves with key technical terminology and possible business models. The case encourages students to see beyond the technical granularities and to consider the multi-faceted, wider corporate and societal issues and priorities. This case contributes to students recognising that business is not conducted in a vacuum and enhances students’ understanding of the role of business in society during new developments triggered by digital technology.
An analysis of survival in patients with castrate-resistant prostate cancer receiving enzalutamide with treatment breaks
Authors: Rowe Michael P , Walter Stuart , Hidayat Ayesha , Pollard Adam , Norris Timothy , Victor Deborah , McGrane John , Thomson Alastair
Published: February 2021

Objective:

Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing.

Methods:

Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned.

Results:

A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001).

Conclusion:

Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further.

Level of evidence:

Level 2c.
Urban form study for wind potential development
Authors: Wang Biao , Geoffroy Sandrine , Bonhomme Marion
Published: February 2021

Wind energy development is helpful for realizing a green city. This work concentrates on the study of estimating urban wind energy with consideration of urban morphology. Fourteen typical urban forms in Beijing city were selected and analyzed with nine relevant urban morphology parameters. Computational fluid dynamics numerical simulations were used to evaluate the wind energy potential of the urban forms. This work demonstrates that urban forms with higher plot ratio and mean aspect ratio usually have higher wind potential density by site area, an important indicator for neighborhood-scale wind potential development. Urban forms with higher average building height would have higher wind potential density by roof area, an important indicator for building-scale wind potential development. To promote wind potential over roofs, a layout of 45° of building configuration with inlet wind direction and building forms with round-angle corners are suggested. Local wind distribution is important for wind energy evaluation of individual buildings and wind energy distribution over different directions; however, it has a substantially lesser effect on the general wind potential comparison among urban forms with different urban characteristics.
Comparison of central corneal thickness measurements with three different optical devices
Authors: Üçer Mehmet Barış , Bozkurt Erdinç
Published: February 2021

Purpose:

The purpose of this study was to compare and evaluate the agreement of central corneal thickness (CCT) values obtained with three different devices working according to optical principle in healthy eyes.

Methods:

60 eyes of 60 individuals (30 men and 30 women) were enrolled in this study. CCT measurements performed with Scheimpflug–Placido topographer (Sirius), spectral-domain optical coherence tomography (RTVue) with an anterior segment module, and optical biometer (AL-Scan) were compared. Bland–Altman analysis was used to demonstrate agreement between methods.

Results:

The mean age was 30.07 ± 7.313 years (range, 18–47 years). The mean CCT values obtained by RTVue, Sirius, and AL-Scan were 518.25 ± 36.38 µm, 526.08 ± 36.33 µm, and 513.50 ± 39.09 µm, respectively. The mean differences in CCT were 7.83 ± 14.15 µm between Sirius and RTVue, 12.58 ± 11.87 µm between Sirius and AL-Scan, and 4.75 ± 4.50 µm between RTVue and AL-Scan. The mean CCT was statistically different among the three groups ( p < 0.05). All three modalities of CCT measurements correlated closely with each other, with Pearson’s correlation coefficients ranging from 0.924 to 0.961. The 95% limits of agreement were −19.90 to 35.56 µm between Sirius and RTVue, −10.69 to 35.85 µm between Sirius and AL-Scan, and −4.07 to 13.58 µm between RTVue and AL-Scan.

Conclusion:

Different results could be obtained through different noncontact devices in CCT measurements. Although the measurement values obtained by these devices show a high level of correlation, it would be a more correct approach to not use them directly interchangeably in clinical practice. Evaluation and follow-up of CCT should be performed using the same device.
The TPOCS-self-reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY): A case study of pragmatic measure development
Authors: Becker-Haimes Emily M , Klein Melanie R , McLeod Bryce D , Schoenwald Sonja K , Dorsey Shannon , Hogue Aaron , Fugo Perrin B , Phan Mary L , Hoffacker Carlin , Beidas Rinad S
Published: February 2021

Background:

Developing pragmatic assessment tools to measure clinician use of evidence-based practices is critical to advancing implementation of evidence-based practices in mental health. This case study details our community-partnered process of developing the Therapy Process Observation Coding Scale-Self-Reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY), a pragmatic, clinician-report instrument to measure cognitive behavioral therapy (CBT) delivery.

Approach:

We describe a five-step community-partnered development process. Initial goals were to create a self-report instrument that paralleled an existing direct observation measure of clinician delivery of CBT use to facilitate later assessment of measure performance. Cognitive interviews with community clinicians ( n = 6) and consultation with CBT experts ( n = 6) were used to enhance interpretability and usability as part of an iterative refinement process. The instrument was administered to 247 community clinicians along with an established self-reported measure of clinician delivery of CBT and other treatments to assess preliminary psychometric performance. Preliminary psychometrics were promising.

Conclusion:

Our community-partnered development process showed promising success and can guide future development of pragmatic implementation measures both to facilitate measurement of ongoing implementation efforts and future research aimed at building learning mental health systems.

Plain language summary

Developing brief, user-friendly, and accurate tools to measure how therapists deliver cognitive behavioral therapy (CBT) in routine practice is important for advancing the reach of CBT into community settings. To date, developing such “pragmatic” measures has been difficult. There is little known about how researchers can best develop these types of assessment tools so that they (1) are easy for clinicians in practice to use and (2) provide valid and useful information about implementation outcomes. As a result, there are few well-validated measures in existence that measure therapist use of CBT that are feasible for use in community practice. This paper contributes to the literature by describing our community-partnered process for developing a measure of therapist use of CBT (Therapy Process Observation Coding Scale -Self-Reported Therapist Intervention Fidelity for Youth; TPOCS-SeRTIFY). This descriptive case study outlines the community-partnered approach we took to develop this measure. This case study will contribute to future research by serving as a guide to others aiming to develop pragmatic implementation measures. In addition, the TPOCS-SeRTIFY is a pragmatic measure of clinician use of CBT that holds promise for its use by both researchers and clinicians to measure the success of CBT implementation efforts.
In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice
Authors: Li Chang , Georgakopoulou Aphrodite , Mishra Arpit , Gil Sucheol , Hawkins R. David , Yannaki Evangelia , Lieber André
Published: February 2021

Base editors are capable of installing precise genomic alterations without creating double-strand DNA breaks. In this study, we targeted critical motifs regulating γ-globin reactivation with base editors delivered via HDAd5/35++ vectors. Through optimized design, we successfully produced a panel of cytidine and adenine base editor (ABE) vectors targeting the erythroid BCL11A enhancer or recreating naturally occurring hereditary persistence of fetal hemoglobin (HPFH) mutations in the HBG1/2 promoter. All 5 tested vectors efficiently installed target base conversion and led to γ-globin reactivation in human erythroid progenitor cells. We observed ~23% γ-globin protein production over β-globin, when using an ABE vector (HDAd-ABE-sgHBG-2) specific to the –113A>G HPFH mutation. In a β-YAC mouse model, in vivo hematopoietic progenitor/stem cell (HSPC) transduction with HDAd-ABE-sgHBG-2 followed by in vivo selection resulted in >40% γ-globin+ erythrocytes in the peripheral blood. This result corresponded to 21% γ-globin production over human β-globin. The average –113A>G conversion in total bone marrow cells was 20%. No alterations in hematological parameters, erythropoiesis, and bone marrow cellular composition were observed after treatment. No detectable editing was found at top-scoring, off-target genomic sites. Bone marrow lineage–negative cells from primary mice were capable of reconstituting secondary transplant-recipient mice with stable γ-globin expression. Importantly, the advantage of base editing over CRISPR/Cas9 was reflected by the markedly lower rates of intergenic HBG1/2 deletion and the absence of detectable toxicity in human CD34+ cells. Our observations suggest that HDAd-vectorized base editors represent a promising strategy for precise in vivo genome engineering for the treatment of β-hemoglobinopathies.
The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation
Authors: Zeng Chong , Shao Zhongbao , Wei Zibo , Yao Jie , Wang Weidong , Yin Liang , YangOu Huixian , Xiong Dan
Published: February 2021

Background

NOTCH signaling has been shown to play a role in the production of interleukin-22 (IL-22) by CD4+ T cells. Multiple T-helper (Th) cell populations secrete IL-22. Th22 (CD4+IL22+IFNγ−IL17A−) cells are a subgroup of CD4+ effector T cells that primarily generate IL-22. The regulatory mechanisms of the NOTCH signaling pathway involved in differentiation of the Th22 cell subset have not been completely elucidated. This study aimed to further explore the involvement of NOTCH signaling in Th22 differentiation.

Methods

In vitro combination of IL-6, IL-23, and tumor necrosis factor-α (TNF-α) treatment with naïve CD4+ T cells established the Th22 cell induced model. NOTCH signaling was activated by jagged-1 and inhibited by (2S)-N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester (DAPT). HES-1 siRNA and HES-1 vector were employed to knock down and induce overexpression of HES-1 to investigate the effect of NOTCH signaling on the differentiation of CD4+T cells into Th22 cells.

Results

We observed that the proportion of Th22 cells, along with Hes-1, Ahr, and Il-22 mRNA and protein expression, was increased by both jagged-1 and overexpression of HES-1. On the other hand, after the combined cytokine treatment of cells, and exposure to jagged-1 and DAPT or HES-1 siRNA, there was a decrease in the Th22 cell proportion, mRNA and protein expression of HES-1, AHR, and IL-22.

Conclusions

Our study demonstrates that HES-1 enhancement in AHR and IL-22 up-regulation of NOTCH signaling can promote the skewing of naïve CD4+T cells toward Th22 cells. Also, the results of our study show that HES-1 is a crucial factor in Th22 cell differentiation.
Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer
Authors: Li Zihaoran , Wu Xinghan , Wang Wenyu , Gai Chengcheng , Zhang Weifen , Li Wentong , Ding Dejun
Published: February 2021

Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.
Automatic reconstruction of metabolic pathways from identified biosynthetic gene clusters
Authors: Sulheim Snorre , Fossheim Fredrik A. , Wentzel Alexander , Almaas Eivind
Published: February 2021

Background

A wide range of bioactive compounds is produced by enzymes and enzymatic complexes encoded in biosynthetic gene clusters (BGCs). These BGCs can be identified and functionally annotated based on their DNA sequence. Candidates for further research and development may be prioritized based on properties such as their functional annotation, (dis)similarity to known BGCs, and bioactivity assays. Production of the target compound in the native strain is often not achievable, rendering heterologous expression in an optimized host strain as a promising alternative. Genome-scale metabolic models are frequently used to guide strain development, but large-scale incorporation and testing of heterologous production of complex natural products in this framework is hampered by the amount of manual work required to translate annotated BGCs to metabolic pathways. To this end, we have developed a pipeline for an automated reconstruction of BGC associated metabolic pathways responsible for the synthesis of non-ribosomal peptides and polyketides, two of the dominant classes of bioactive compounds.

Results

The developed pipeline correctly predicts 72.8% of the metabolic reactions in a detailed evaluation of 8 different BGCs comprising 228 functional domains. By introducing the reconstructed pathways into a genome-scale metabolic model we demonstrate that this level of accuracy is sufficient to make reliable in silico predictions with respect to production rate and gene knockout targets. Furthermore, we apply the pipeline to a large BGC database and reconstruct 943 metabolic pathways. We identify 17 enzymatic reactions using high-throughput assessment of potential knockout targets for increasing the production of any of the associated compounds. However, the targets only provide a relative increase of up to 6% compared to wild-type production rates.

Conclusion

With this pipeline we pave the way for an extended use of genome-scale metabolic models in strain design of heterologous expression hosts. In this context, we identified generic knockout targets for the increased production of heterologous compounds. However, as the predicted increase is minor for any of the single-reaction knockout targets, these results indicate that more sophisticated strain-engineering strategies are necessary for the development of efficient BGC expression hosts.
Correction to: Multi‑modality biomarkers in the early prediction of ischaemic heart disease in middle‑aged men during a 21‑year follow‑up
Authors: Sakalaki Maria , Hansson Per-Olof , Rosengren Annika , Thunström Erik , Pivodic Aldina , Fu Michael
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
An unusual tracheal foreign body in a middle-aged male with a 15-year history of coal use: a case report
Authors: Zhong Li-juan , Yan Min , Wang Yi , Zhou Dai-quan , Tang Jian-ming , Xiang Shou-hong
Published: February 2021

Background

Long-term exposure to coal dust causes respiratory disease. In chest computer tomography (CT), pulmonary nodules, pulmonary interstitial fibrosis and emphysema manifest themselves. However, tracheal foreign bodies caused by coal dust are rarely reported. In this study, we report a special case of a tracheal coal foreign body, in which the patient has neither a history of coal work nor foreign body inhalation.

Case presentation

A 49-year-old man was diagnosed with chronic obstructive pulmonary disease (COPD) due to chronic cough and exertional dyspnoea. His symptoms gradually worsened despite treatment for COPD. Chest radiograph and CT images showed an irregular high-density nodule inserting fromthe trachea into the right thyroid at approximately the level of the 7th cervical vertebra. Fiberoptic bronchoscopy revealed that the tracheal lumen was mostly blocked. After the surgery, the energy spectrum CT quantitative analysis showed that the foreign body was likely that of a bituminous coal specimen.

Conclusions

For cases in which a foreign body in the airway is highly suspected, early fiberoptic bronchoscopy and radiographic examinations should be performed as soon as possible to avoid misdiagnosis and ensure timely treatment.