bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of COVID-19 on antipsychotic prescriptions for patients with schizophrenia in Australia
Authors: Kisely Steve , Dangelo-Kemp Dante , Taylor Mark , Liu Dennis , Graham Simon , Hartmann Jodie , Colman Sam
Published: July 2021

Objective:

To assess the impact, in the Australian setting, of the COVID-19 lockdown on antipsychotic supplies for patients with schizophrenia following a prescription from a new medical consultation when compared to the same periods in the previous 4 years. A secondary objective was to assess the volume of all antipsychotic supplies, from new and repeat prescriptions, over these same periods.

Methods:

A retrospective pharmaceutical claims database study was undertaken, using the Department of Human Services Pharmaceutical Benefits Scheme 10% sample. The study population included all adult patients with three or more supplies of oral or long-acting injectable antipsychotics for the treatment of schizophrenia at any time between 1 June 2015 and 31 May 2020. The primary outcome compared volumes of dispensed antipsychotics from new prescriptions (which require a medical consultation) between 1 April and 31 May each year from 2016 to 2020. This was to analyse the period during which the Australian Government imposed a lockdown due to COVID-19 (April to May 2020) when compared the same periods in previous years.

Results:

There was a small (5.7%) reduction in the number of antipsychotics dispensed from new prescriptions requiring a consultation, from 15,244 to 14,372, between April and May 2019 and the same period in 2020, respectively. However, this reduction was not statistically significant ( p = 0.75) after adjusting for treatment class, age, gender, location and provider type.

Conclusion:

The COVID-19 restrictions during April and May 2020 had no significant impact on the volume of antipsychotics dispensed from new prescriptions for patients with schizophrenia when compared to the volume of antipsychotics dispensed from new prescriptions during the same period in previous years.
The Moderating Effect of Emotional Intelligence on Problematic Internet Use and Cyberbullying Perpetration Among Adolescents: Gender Differences
Authors: Yudes Carolina , Rey Lourdes , Extremera Natalio
Published: July 2021

A large body of literature has identified the problematic Internet use as a risk factor for cyberbullying perpetration. Nevertheless, the studies on protective factors that may moderate this relationship are still scarce. The purpose of the present study was to examine if the emotional intelligence is a moderator in the relationship between problematic Internet use and cyberbullying perpetration. A total of 2039 Spanish adolescents between 12 to 18 years filled out three self-report questionnaires to evaluate these variables. Results indicated that cyberbullying perpetration was positively associated with problematic Internet use and negatively with emotional intelligence. On the other hand, problematic Internet use was negatively related to emotional intelligence, being this relationship stronger in girls. With respect to the possible buffering effect, emotional intelligence moderated the relation between problematic Internet use and cyberbullying perpetration in boys, especially at lower levels. These findings suggest that emotional intelligence is a personal resource which have an important protective role for the problematic Internet use in adolescents. Implications for the preventive interventions of cyberbullying perpetration are discussed.
Importance of brain alterations in spinal cord injury
Authors: Zhao Can , Bao Shu-Sheng , Xu Meng , Rao Jia-Sheng
Published: July 2021

Spinal cord injury (SCI) destroys the sensorimotor pathway and blocks the information flow between the peripheral nerve and the brain, resulting in autonomic function loss. Numerous studies have explored the effects of obstructed information flow on brain structure and function and proved the extensive plasticity of the brain after SCI. Great progress has also been achieved in therapeutic strategies for SCI to restore the “re-innervation” of the cerebral cortex to the limbs to some extent. Although no thorough research has been conducted, the changes of brain structure and function caused by “re-domination” have been reported. This article is a review of the recent research progress on local structure, functional changes, and circuit reorganization of the cerebral cortex after SCI. Alterations of structure and electrical activity characteristics of brain neurons, features of brain functional reorganization, and regulation of brain functions by reconfigured information flow were also explored. The integration of brain function is the basis for the human body to exercise complex/fine movements and is intricately and widely regulated by information flow. Hence, its changes after SCI and treatments should be considered.
Duplicity behind Stained Glass: Childlike “Self-knowledge” and the Role of Community
Authors: Wrigley-Carr Robyn
Published: July 2021

The recent revelation of Jean Vanier (1928–2019) and historical cases of sexual manipulation and abuse of six women workers at L’Arche (Trosly-Breuil, France, 1970–2005) is a reminder of our human fragility. This article explores the question of how we, as people working in religion, can seek greater integration so as to avoid, as far as possible, the self-deception and duplicity that can lead to profound harm of others. Through engaging with two theologians—Teresa of Avila (1515–1582) and George MacDonald (1824–1905)—we gain insights concerning discernment of our blind spots, plus wisdom regarding ways to safeguard ourselves from duplicity. Teresa reminds us of the need to continually develop authentic “self-knowledge,” and the importance of a courageous, discerning community—both a perceptive spiritual director and honest peers who are willing to challenge leaders and speak up. MacDonald highlights the need for spiritual discernment and a “childlike” posture (rather than self-elevation to a revered “guru” status), to help us live more integrated, genuine lives. Both dialogue partners are explicitly Christocentric and emphasize the ongoing work of the Spirit, opening our eyes and ears to the reality of who we truly are, and the importance of imitating and being “in Christ,” in order to be freed from self-obsession, duplicity, and self-deception.
Exhibitionary Commerce, the Construction of Whiteness, and the Theological Sideshow
Authors: Powell Lisa D.
Published: July 2021

I will briefly recount the histories of three individuals who were exhibited for White audiences, to consider the role that the White spectator has in the construction of White supremacist ideology that casts Whiteness as norm and Blackness as deviant curiosity. Drawing from womanist scholarship, I will argue that the White theological canon and White-centric scholarship actively perpetuate this legacy. In conclusion I analyze the theology syllabi collected in the Wabash/AAR database to expose the ongoing construction of White supremacist ideologies within the theology classroom.
Diagnostic Performance of Muscle Echo Intensity and Fractal Dimension for the Detection of Frailty Phenotype
Authors: Mirón Mombiela Rebeca , Vucetic Jelena , Monllor Paloma , Cárdenas-Herrán Jenny S. , Taltavull de La Paz Paloma , Borrás Consuelo
Published: July 2021

To determine the relationship between muscle echo intensity (EI) and fractal dimension (FD), and the diagnostic performance of both ultrasound parameters for the identification of frailty phenotype. A retrospective interpretation of ultrasound scans from a previous cohort (November 2014–February 2015) was performed. The sample included healthy participants <60 years old, and participants ≥60 divided into robust, pre-frail, and frail groups according to Fried frailty criteria. A region of interest of the rectus femoris from the ultrasound scan was segmented, and histogram function was applied to obtain EI. For fractal analysis, images were processed using two-dimensional box-counting techniques to calculate FD. Statistical analyses were performed with diagnostic performance tests. A total of 102 participants (mean age 63 ± 16, 57 men) were evaluated. Muscle fractal dimension correlated with EI ( r = .38, p < .01) and showed different pattern in the scatter plots when participants were grouped by non-frail (control + robust) and frail (pre-frail + frail). The diagnostic accuracy for EI to categorize frailty was of 0.69 (95%CI: 0.59–0.78, p = .001), with high intra-rater (ICC: 0.98, 95%CI: 0.98–0.99); p < .001) and inter-rater (ICC: 0.89, 95%CI: 0.75–0.95; p < .001) reliability and low measurement error for both parameters (EI: −0.18, LOA95%: −10.8 to 10.5; FD: 0.00, LOA95%: −0.09 to 0.10) in arbitrary units. The ROC curve combining both parameters was not better than EI alone ( p = .18). Muscle FD correlated with EI and showed different patterns according to frailty phenotype, with EI outperforming FD as a possible diagnostic tool for frailty.
Role reversal in remote peer supervision: Utilising tools commonly used in dramatherapy and family therapy to facilitate peer supervision
Authors: Iordanou Christiana , Rapanou Spyridoula
Published: July 2021

Peer supervision is a dynamic process which highlights constructive and supportive feedback among therapists while minimising feelings of being evaluated. Some of its benefits include decreased dependency on the expertise of a supervisor, freedom, and equality. In this article, we outline the benefits of peer supervision between a dramatherapist and a family therapist and how their common roots based on creativity and action-based approaches could be used remotely to enhance the goals of peer supervision. We discuss how we utilised such methods and more specifically role reversal in a virtual space during the first Covid-19 lockdown to facilitate the process of peer supervision and understand better the needs and perspective of the client. We propose that incorporating creative and spontaneous methods such as role reversal in a virtual peer supervision environment can potentially enhance the supervisory alliance and therapeutic practice.
The geopolitical hijacking of open networking: the case of Open RAN
Authors: Plantin Jean-Christophe
Published: July 2021

This article investigates how discourses on open networking technologies provide a social imaginary that industry and government actors mobilize in an attempt to expand their control over mobile telecommunications networks. The case of recent initiatives aiming to ‘open up’ radio access network (or RAN, a key component of telecommunications infrastructure) with an ‘open RAN’ model reveals how the US Government came to promote this nascent technology to create an opposition between its own ‘open’ telecommunications networks versus proprietary and presumed ‘untrustworthy’ networks based on foreign equipment, namely Huawei. While a closer look casts doubts on the benefits of open radio access network to increase network security or to open up the equipment market, this case reveals how openness is an ambiguous notion that can be used by governments to exclude foreign trade enemies, while advocating for trust in telecommunications networks.
Relations between shear flow and vortices in the near wake of a high speed train
Authors: Pan Yong-chen , Yao Jian-wei , Xu Rui , Liu Tao , Zheng Jun , Li Chang-feng
Published: July 2021

Two flow cases for high speed train models with different lengths have been numerically computed by performing the improved delayed detached-eddy simulation. Based on the Omega method and turbulence production (TP) distribution, the relations between the shear flow and vortices in the near turbulent wake of a high speed train have been comparatively analyzed. First, in the wake region immediately close to the tail, the boundary layer separation plays significant roles. And the mechanism makes shear deformation prominent in the region with the formed vortices. Moreover, the shear layers are pertinent to the boundary-layer thicknesses and help to the TP distribution. However, the shear-dominated region is very limited due to high dissipation. One the other hand, a vast majority of the vortices captured with the parameter Omega increasing in the downstream region away from the tail. And the TP distributions are stable at different streamwise positions, though obviously decreased. They are greatly attributed to the mean strain rate in the horizontal plane. Meanwhile, the vortical vorticity is thought to be the dominant component inside the vortex cores, although the shear becomes weaker. And thus the turbulence itself can be spatially sustained due to the relatively stable vortex structure. Moreover, the weak shear is believed to depend upon the interaction between the vortices and the ground.
One step forward, two steps back? Shifting patterns of participation in a former informal settlement in Mexico City
Authors: Silvonen Taru
Published: July 2021

While advances in participatory planning have led in many cases to the more inclusive rebuilding of informal settlements, the debate regarding participatory planning has focused largely on the improvement of current informal settlements without asking “what next”. Declining living conditions following settlement consolidation, however, provide evidence of the potential shortfalls of temporary participatory approaches. Drawing on an ethnographic case study of a former informal settlement in Iztapalapa, Mexico City, this paper analyses the erosion of resident participation in neighbourhood development over 40 years. Comparisons between residents’ accounts of neighbourhood formation, mostly in the 1980s, and contemporary experiences show a gradual decrease in resident engagement. The data collected in 2016–2017 highlight this diminishing local participation and suggest that the disappearance of earlier local practices of engagement is linked in various ways to the failure of formally supported practices of citizen participation. The paper shows what can be learnt from residents’ memories of transforming informal settlements.
Conceptualizing contemporary markets: Introduction to the special issue
Authors: Gruin Julian , Massot Pascale
Published: July 2021

Contemporary markets are evolving in numerous ways that affect their structure, dynamics and consequences. Yet while the concept of the market is central to comparative, international and global political economy, there exists no concerted body of literature dedicated to debating and articulating different conceptions of the market and that critically self-reflects on how these empirical transformations are intersecting with the central theoretical concerns of political economy: power, contestation and change. This special issue enriches the debate by looking to decentre the concept of the market from its traditional home in mainstream neoclassical/liberal political economy. Western-centric conceptualizations of the market based on a minimal atomistic classical definition have dominated international economic discourses but it is becoming increasingly clear that different understandings of markets and the functions they serve are crystalizing between market stakeholders at the global level. This special issue addresses these concerns via the historicization of the concept of the market, the development and refinement of the concept of the market, as well as the decentring of the concept of the market via empirical studies of global market change informed by an awareness of the political, economic, social and cultural embeddedness of markets. In so doing, the special issue leverages the insights of global political economy and cognate disciplines to achieve richer insights into the analytical potential of the concept of the market.
Does respiratory variation in inferior vena cava diameter predict fluid responsiveness in adult patients? A systematic review and meta-analysis of diagnostic accuracy studies
Authors: Unal Akoglu Ebru , Akoglu Haldun
Published: July 2021

Objectives:

To systematically review the diagnostic utility of the respiratory variation of the inferior vena cava diameter measured using ultrasonography for predicting fluid responsiveness in adult patients and compare the three commonly used equations, inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability.

Methods:

We searched PubMed, Scopus, Web of Science and Cochrane library, and included studies investigating the diagnostic accuracy of the respiratory variation of the inferior vena cava measured using ultrasonography compared to a reference standard for measuring cardiac output after a fluid challenge for fluid responsiveness, and stratified participants as fluid responsive or not. We included studies conducted in the emergency department or intensive care unit. We excluded studies on paediatric, prehospital, cancer, pregnant, dialysis patients or healthy volunteers.

Results:

We retrieved 270 records and excluded 171 because of irrelevance, patient population or publication type. We screened the abstracts of 99 studies and then the full texts of 42 studies. Overall, 21 studies with 1321 patients were included, of whom 689 (52%) were fluid responsive. The mean threshold value for positive inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability was 17%, 35% and 12%, respectively. The heterogeneity between studies was high. Bivariate diagnostic random-effects meta-analysis was used to calculate the summary receiver operating characteristics curves. The overall accuracy, sensitivity and specificity of respiratory variation of the inferior vena cava diameter were 0.85, 0.72 and 0.81, respectively. The accuracy of inferior vena cava distensibility and inferior vena cava collapsibility was similar. The diagnostic utility of respiratory variation of the inferior vena cava diameter was lower but not statistically significant in mechanically ventilated patients compared with spontaneous breathing for predicting fluid responsiveness.

Conclusion:

The respiratory variation of the inferior vena cava diameter has moderate diagnostic utility for predicting fluid responsiveness independent of the equation used.
Automated glaucoma detection from fundus images using wavelet-based denoising and machine learning
Authors: Khan Sibghatullah I. , Choubey Shruti Bhargava , Choubey Abhishek , Bhatt Abhishek , Naishadhkumar Pandya Vyomal , Basha Mohammed Mahaboob
Published: July 2021

Glaucoma is a domineering and irretrievable neurodegenerative eye disease produced by the optical nerve head owed to extended intra-ocular stress inside the eye. Recognition of glaucoma is an essential job for ophthalmologists. In this paper, we propose a methodology to classify fundus images into normal and glaucoma categories. The proposed approach makes use of image denoising of digital fundus images by utilizing a non-Gaussian bivariate probability distribution function to model the statistics of wavelet coefficients of glaucoma images. The traditional image features were extracted followed by the popular feature selection algorithm. The selected features are then fed to the least square support vector machine classifier employing various kernel functions. The comparison result shows that the proposed approach offers maximum classification accuracy of nearly 91.22% over the existing best approaches.
Work Engagement and Patient Quality of Care: A Meta-Analysis and Systematic Review
Authors: Wee Kenneth Z. , Lai Alden Yuanhong
Published: July 2021

Past research has demonstrated that work engagement among health care professionals influences patient quality of care. There is, however, no estimate of the strength of this relationship, and existing reviews have not always explained conflicting findings. We conduct a meta-analysis and review of 25 articles, and find a small to medium mean effect size ( r = .26, p < .01) for the positive association between engagement and quality of care. Moderator analyses on five factors (type, data source, level of analysis of the quality of care measure, profession, and work engagement measure) indicate that only data source is significant, providing preliminary evidence that the relationship is stronger if quality of care is measured via self-assessments. Although a more consistent conceptualization of quality of care is needed to better determine its association with work engagement, our findings suggest that work engagement is as important as burnout in predicting quality of care.
‘Ignoring the elephant in the room’: (Under-)representation of impoliteness phenomenon in popular ELT textbooks
Authors: Talebzadeh Hossein , Khazraie Marzieh
Published: July 2021

One of the underrepresented aspects of pragmatic competence development is perceiving and responding to impoliteness acts. The present study reports on a quantitative and qualitative investigation of two international English language teaching (ELT) textbook series published by Oxford and Cambridge University Press; it focuses on the books highly popular among a thriving representative sample of learners of English as a foreign language (EFL) across four language proficiency levels and explores their coverage and treatment of impoliteness acts and their responses. Drawing on stringent models and taxonomies, the findings reveal that this unpleasant side of language is ignored and misrepresented in the textbooks, particularly at lower proficiency levels. We draw on our own and others’ previous incivility studies and argue for the inclusion of impoliteness especially from earlier stages of language learning owing to its saliency in authentic interactions. The study concludes with implications and suggestions for language learners, instructors, textbook writers, and researchers.
This Is a Secret: Learning From Children’s Engagement With Surveillance and Secrecy
Authors: Kaufmann Mareile
Published: July 2021

This article establishes the relevance of surveillance and secrecy as methodological tools, and it substantiates the argument that surveillance and secrecy are not oppositional in character, but overlap. It does so by drawing attention to obvious, but scholarly neglected performers of secrecy and surveillance: children. It discusses what it means to “work with” surveillance and secrecy as it develops their relevance in case studies involving children. As a contribution to cultural studies, the article shows how surveillance and secrecy “get to work” by tracing their constitutive character and by providing new angles for understanding points of contact between the two.
Agency: The Force and Compass of Transformation
Authors: Green Larry
Published: July 2021

Mezirow’s theory of transformative learning presupposes agency. Agency is the means by which the limitations of an inadequate meaning perspective are transcended. It is the creative activity necessitated by an encounter with a disorienting dilemma. This implies that transformation cannot be achieved from within the existent meaning perspective. It can only be exercised from outside that constellation of constructs. This depends on the person dissociating from that perspective in order to enter a groundless state where originary thought is possible. In that state, they have access to an impersonal consciousness. That impersonal consciousness, which constructed the problematic meaning perspective, is now utilized for designing a more adequate one. These processes are accompanied by associated affects. For example, anxiety is the affect associated with groundlessness whereas depression with the lack of agency. I suggest that agency arises when the situation demands it and falls away after the dilemma has been addressed.
A Simple Novel Method to Elevate the Sternum in Thoracoscopic Thymectomy
Authors: Jia Renxiang , Sun Shizhu , Wang Ziyi , Ren Yi
Published: July 2021

The right-chest thoracoscopic surgery approach has become the preferred operation for the treatment of thymic disease. Due to the limited space in the anterior mediastinum, achieving en bloc resection of the tumor is a common difficulty. Here, we report a simple method to lift the sternum by single hook. This method has a lot of advantages, including providing a wide view of the anterior mediastinum for clear vision and being an easy operation.
Less Invasive Pediatric Spinal Deformity Surgery: The Case for Robotic-Assisted Placement of Pedicle Screws
Authors: Morse Kyle W. , Otremski Hila , Page Kira , Widmann Roger F.
Published: July 2021

Introduction: Pediatric spinal deformity involves a complex 3-dimensional (3D) deformity that increases the risk of pedicle screw placement due to the close proximity of neurovascular structures. To increase screw accuracy, improve patient safety, and minimize surgical complications, the placement of pedicle screws is evolving from freehand techniques to computer-assisted navigation and to the introduction of robotic-assisted placement. Purpose: The aim of this review was to review the current literature on the use of robotic navigation in pediatric spinal deformity surgery to provide both an error analysis of these techniques and to provide recommendations to ensure its safe application. Methods: A narrative review was conducted in April 2021 using the MEDLINE (PubMed) database. Studies were included if they were peer-reviewed retrospective or prospective studies, included pediatric patients, included a primary diagnosis of pediatric spine deformity, utilized robotic-assisted spinal surgery techniques, and reported thoracic or lumbar pedicle screw breach rates or pedicle screw malpositioning. Results: In the few studies published on the use of robotic techniques in pediatric spinal deformity surgery, several found associations between the technology and increased rates of screw placement accuracy, reduced rates of breach, and minimal complications. All were retrospective studies. Conclusions: Current literature is of a low level of evidence; nonetheless, the findings suggest the accuracy and safety of robotic-assisted spinal surgery in pediatric pedicle screw placement. The introduction of robotics may drive further advances in less invasive pediatric spinal deformity surgery. Further study is warranted.
Thermal and breathability management of microencapsulated phase change material (MPCM) incorporated jute fabric
Authors: Shahid Abdus , Miah Solaiman , Rahim Abdur
Published: July 2021

Jute bags are widely used to carry food grains and other materials that may be prone to quality deterioration due to thermal fluctuation. Thermal and moisture properties play a significant role in the packaging materials in the form of a container. This study deals with the effect of microencapsulated phase change material (MPCM) with hydrophobic binder on thermal and moisture management properties of jute fabric. Jute fabric was treated with MPCM by pad-dry-cure method. The treated sample was characterized by thermogravimetric analysis (TGA), differential scanning colorimeter (DSC), scanning electron microscope (SEM), moisture management tester (MMT), and air permeability tester. The results revealed that MPCM treated jute fabric shows greater thermal stability and heat absorption ability of 10.58 J/g while changing from solid to liquid phase. The SEM image ensures even distribution of MPCMs on fabric surface and surface roughness was also observed using image processing software. The air permeability was found to decrease whereas the water repellency enhanced in the developed sample.
Exploring visual method in the field of educational leadership: Co-creating understandings of educational leadership and authority in school organisations
Authors: Grimm Frida , Norqvist Lars , Roos Katarina
Published: July 2021

This paper contributes to method development in educational leadership research. The focus is on a visual method and the inclusion of visual material in data collection and analysis. Core concepts in this paper are educational leadership, power and authority. The method was used in face-to-face interviews in a research project that studied the steering and governing in, and of, Swedish schools. The method enhances verbal narratives when informants reason and motivate their understandings of positions, relations and hierarchies within the organisations. We found that using visual material encouraged informants to reason and problematise formalised leader positions, their relations and the hierarchies that appear. The method helps to visualise the informants’ understandings of the power distribution within the organisation depending on whether positions are described as distant or close, horizontal or vertical. The method made the informants take a stand on complex matters, reflect, and gain insights about their organisations. It provided us, as researchers, with rich data material. By making subjective understandings visual, implicit assumptions were made explicit. This could challenge the knowledge on existing leadership and power norms within educational organisations, and most likely in other forms of organisations as well.
Design and analysis of a Cross Car frame. Proposal of a three-level appraisal methodology
Authors: Luque Pablo , Gutierrez Alex , Rodríguez Eduardo , Mántaras Daniel A
Published: July 2021

This paper analyses the structural design process of a Cross Car frame. Existing international and national technical regulations were analysed. The analysis of the regulatory guidelines led to the conclusion that the design only includes geometric or material restrictions at the international level. There are other more demanding national regulations (Spanish, for instance) that include structural verifications through static calculations for unidirectional actions (vertical, longitudinal or lateral). The main contribution of this paper is a novel three-level appraisal and a proposed redesign methodology. At the first level, a geometric and material verification is carried out. The second level involves the verification under unidirectional static actions. The third level entails a dynamic verification of three-dimensional combined actions. The load case is obtained from the computer multibody dynamics simulation of the full vehicle assembly in the worst case of driving conditions on circuits. This methodology is a far more detailed tool than traditional design processes. The use of this methodology allows for design optimisation, including all the effects of powertrain, brakes, suspension, steering and driver.
Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study
Authors: Zhao Yannan , Xie Ning , Li Wei , Chen Wenyan , Lv Zheng , Zheng Yabing , Sun Tao , Liu Jieqiong , Zhang Jian , Hu Shihui , Wang Yajun , Gong Chengcheng , Li Yi , Xie Yizhao , Ge Rui , Xu Fei , Wang Biyun
Published: July 2021

Background:

Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice.

Patients and Methods:

A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0.

Results:

Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia.

Conclusion:

Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.
Shockwave Treatment Enhanced Extracellular Matrix Production in Articular Chondrocytes Through Activation of the ROS/MAPK/Nrf2 Signaling Pathway
Authors: Shen Po-Chih , Chou Shih-Hsiang , Lu Cheng-Chang , Huang Hsuan-Ti , Chien Song-Hsiung , Huang Peng-Ju , Liu Zi-Miao , Shih Chia-Lung , Su Shu-Jem , Chen Li-Min , Tien Yin-Chun
Published: July 2021

Objective

Shockwave application is a potential treatment for osteoarthritis (OA), but the underlying mechanism remains unknown. Oxidative stress and a counterbalancing antioxidant system might be the key to understanding this mechanism. We hypothesized that reactive oxygen species (ROS) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),which is an important regulator of cellular redox homeostasis, are plausible elements.

Design

Porcine chondrocytes were cultured in a 3-dimensional pellet model and subjected to shockwaves. The effects of shockwaves with various energy-flux densities on optimal extracellular matrix (ECM) synthesis were assessed. ROS, mitogen-activated protein kinase (MAPK) signaling, and the redox activity of Nrf2 were measured. To investigate the signaling mechanism involved in the shockwave treatment in chondrocytes, specific inhibitors of ROS, MAPK signaling, and Nrf2 activity were targeted.

Results

Shockwaves increased ECM synthesis without affecting cell viability or proliferation. Furthermore, they induced transient ROS production mainly through xanthine oxidase. The phosphorylation of ERK1/2 and p38 and the nuclear translocation of Nrf2 were activated by shockwaves. By contrast, suppression of ROS signaling mitigated shockwave-induced MAPK phosphorylation, Nrf2 nuclear translocation, and ECM synthesis. Pretreatment of chondrocytes with the specific inhibitors of MEK1/2 and p38, respectively, mitigated the shockwave-induced nuclear translocation of Nrf2 and ECM synthesis. Nrf2 inhibition by both small hairpin RNA knockdown and brusatol reduced the shockwave-enhanced ECM synthesis.

Conclusions

Shockwaves activated Nrf2 activity through the induction of transient ROS signaling and subsequently enhanced ECM synthesis in chondrocytes. This study provided fundamental evidence confirming the potential of shockwaves for OA management.
ASSERT (Acute Sacral inSufficiEncy fractuRe augmenTation): Perceptions in the Assessment and Treatment of Pubic Rami and Sacral Fragility Fractures Amongst Healthcare Professionals in Geriatric Medicine and Surgery—A Qualitative Study
Authors: Sahota Opinder , Leighton Paul , Cameron Maribel , Taylor Rachael , Ong Terence , Drummond Avril , Hendrick Paul , Quraishi Nasir , Salem Khalid ,   On Behalf of the ASSERT Research Team
Published: July 2021

Background:

Pubic rami fragility fractures are common in older people and result in significant morbidity and increased mortality. Co-existing fractures of the sacrum are common, but routinely missed. The aim of the study was to explore the perceptions in the assessment and treatment of pubic rami and sacral fragility fractures amongst healthcare professionals.

Methods:

We interviewed 14 participants about their experience in the assessment and treatment of patients presenting with pubic rami fragility fractures. Data was analyzed using an inductive thematic approach.

Results:

The majority of patients presenting with a pubic rami fragility fracture were managed by geriatricians. However, many of the geriatricians were not aware that these fractures have a high association with co-existing sacral fragility fractures. Furthermore, they were not aware of the limitations of standard x-ray imaging, nor of the potential benefits of surgical intervention for sacral fragility fractures. Spinal surgeons recommended that early, more specialist imaging in patients with pubic rami fragility fractures failing to mobilize, would change clinical management, if found to have a coexisting sacral fragility fracture, amenable to surgical intervention.

Conclusions:

The awareness, assessment and management of sacral fragility fractures in patients presenting with pubic rami fragility fractures is poor amongst healthcare professionals in geriatric medicine. Spinal surgeons in this study advocate early further imaging and surgical intervention in patients confirmed to have a concomitant sacral fragility fracture who are failing to mobilize.
One Program Fits All? Patterns and Outcomes of Professional Development During a Large-Scale Reform in a High-Stakes Science Curriculum
Authors: Hübner Nicolas , Fischer Christian , Fishman Barry , Lawrenz Frances , Eisenkraft Arthur
Published: July 2021

When translating large-scale policy changes into educational practice, classroom-level implementation is crucial and dependent on teachers’ capabilities. Most research underscores the importance of professional development (PD) as a proximal factor to achieve educational change. Connected to the recent Advanced Placement (AP) science examination reform, this large-scale quantitative study (NTeachers = 9,096; NStudents = 197,589) investigates teacher participation in different PD formats (i.e., face-to-face, online, materials) and their associations with teacher- and student-level outcomes. We found that teacher characteristics (e.g., gender and administrative support) were associated with the choice of the PD format. We also found AP subscore differences between students of teachers who participated in different PD formats. Furthermore, teachers who participated in formal PD activities tended to report higher challenges with the AP reform. Thus, this study encourages PD providers to implement changes alongside a variety of PD programs to account for the potential differential benefits for teachers.
Pangenome analysis and virulence profiling of Streptococcus intermedius
Authors: Sinha Dhiraj , Sun Xifeng , Khare Mudra , Drancourt Michel , Raoult Didier , Fournier Pierre-Edouard
Published: July 2021

Background

Streptococcus intermedius, a member of the S. anginosus group, is a commensal bacterium present in the normal microbiota of human mucosal surfaces of the oral, gastrointestinal, and urogenital tracts. However, it has been associated with various infections such as liver and brain abscesses, bacteremia, osteo-articular infections, and endocarditis. Since 2005, high throughput genome sequencing methods enabled understanding the genetic landscape and diversity of bacteria as well as their pathogenic role. Here, in order to determine whether specific virulence genes could be related to specific clinical manifestations, we compared the genomes from 27 S. intermedius strains isolated from patients with various types of infections, including 13 that were sequenced in our institute and 14 available in GenBank.

Results

We estimated the theoretical pangenome size to be of 4,020 genes, including 1,355 core genes, 1,054 strain-specific genes and 1,611 accessory genes shared by 2 or more strains. The pangenome analysis demonstrated that the genomic diversity of S. intermedius represents an “open” pangenome model. We identified a core virulome of 70 genes and 78 unique virulence markers. The phylogenetic clusters based upon core-genome sequences and SNPs were independent from disease types and sample sources. However, using Principal Component analysis based on presence/ absence of virulence genes, we identified the sda histidine kinase, adhesion protein LAP and capsular polysaccharide biosynthesis protein cps4E as being associated to brain abscess or broncho-pulmonary infection. In contrast, liver and abdominal abscess were associated to presence of the fibronectin binding protein fbp54 and capsular polysaccharide biosynthesis protein cap8D and cpsB.

Conclusions

Based on the virulence gene content of 27 S. intermedius strains causing various diseases, we identified putative disease-specific genetic profiles discriminating those causing brain abscess or broncho-pulmonary infection from those causing liver and abdominal abscess. These results provide an insight into S. intermedius pathogenesis and highlights putative targets in a diagnostic perspective.
Development of a liquid biopsy based purely quantitative digital droplet PCR assay for detection of MLH1 promoter methylation in colorectal cancer patients
Authors: Wang Danyi , O’Rourke Dennis , Sanchez-Garcia Jorge F. , Cai Ti , Scheuenpflug Juergen , Feng Zheng
Published: July 2021

Background

MutL Homolog 1 (MLH1) promotor methylation is associated with microsatellite instability high colorectal cancer (CRC). The strong correlation between methylation status and cancer development and progression has led to a growing interest in the use of methylation markers in circulating tumor DNA (ctDNA) for early cancer detection and longitudinal monitoring. As cancer-specific DNA methylation changes in body fluids are limited, it is particularly challenging to develop clinically applicable liquid biopsy methodologies with high sensitivity and specificity. The purpose of this study was to develop a fit-for-purpose methylation sensitive restriction enzyme (MSRE) based digital droplet PCR (ddPCR) assay to examine MLH1 promoter methylation in ctDNA in advanced CRC.

Methods

Primers and probes were designed to amplify CpG sites of the MLH1 promoter. Methylated and unmethylated control genomic DNA were sheared to mimic ctDNA and subjected to MSRE HpaII digestion. Plasma samples from 20 healthy donors and 28 CRC patients were analyzed with the optimized MSRE procedure using ddPCR.

Results

Using methylated and unmethylated controls, we optimized the conditions for HpaII enzyme digestion to ensure complete digestion and avoid false positives. Based on the results from the ddPCR assay using 1 ng circulating cell-free DNA (cfDNA) input from healthy donors or CRC samples, ROC curves were generated with an area under the curve (AUC) value of 0.965 (95% CI: 0.94, 0.99). The statistically optimal assay sensitivity and specificity was achieved when 8 positive droplets were used as acceptance criteria (78% sensitivity and 100% specificity, 95% CI: 0.45, 0.95). A tiered-based cutoff (20, 50, 80% percentile based) was applied to distinguish CRC samples with different methylation level.

Conclusions

Our study demonstrated that the liquid biopsy assay for MLH1 promoter methylation detection using purely quantitative ddPCR is a simple and highly sensitive procedure that provides reliable methylation detection in ctDNA. The MSRE ddPCR approach can also be applied to other genes of interest where methylation patterns could reveal clinically relevant information for future clinical biomarker and/or companion diagnostic development.
Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)
Authors: Nakayama Takahiro , Yoshinami Tetsuhiro , Yasojima Hiroyuki , Kittaka Nobuyoshi , Takahashi Masato , Ohtani Shoichiro , Kim Seung Jin , Kurakami Hiroyuki , Yamamoto Naoko , Yamada Tomomi , Takata Takehiko , Masuda Norikazu
Published: July 2021

Background

Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer.

Methods

In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken.

Results

Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months.

Conclusions

In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings.

Trial registration

UMIN000038296; registered on 15 October 2019.