bluuebunny/crossref_metadata_2025 huggingface dataset:
Seeing Is Believing: The Role of Place in Mitigating Partisan Attitudes Toward the Environment
Authors: Bromley-Trujillo Rebecca , Ciuk David J. , Kirkpatrick Andrew B. , Bitecofer Rachel
Published: December 2023

Over the past decade the partisan divide over environmental issues has widened significantly. Although attitudes toward climate change and other environmental policy issues have become highly polarized, it is possible that personal geography may moderate partisan attitudes. This study considers whether residing in coastal Virginia influences attitudes on environmental issues among Virginians. To test this question, we survey Virginia registered voters on a range of coastal environmental issues and consider whether place of residence has an effect on these attitudes when accounting for other factors including partisanship. We find a significant relationship between place of residence and a wide range of environmental issue attitudes, though the impact of partisanship is moderated in only limited cases. This research builds on the policy process literature concerning individual proximity to policy problems, place-attachment, and the relationship between partisanship and state environmental policy attitudes.
Decentring critical theory with the help of critical theory: Ecocide and the challenge of anthropocentricism
Authors: Cooke Maeve
Published: December 2023

Our present situation of anthropogenic ecological disaster calls on Western philosophy in general, and Frankfurt School critical theory in particular, to reconsider some long-standing, entrenched assumptions concerning what it means to be a human agent and to relate to other agents. In my article, I take up the challenge in dialogue with the idea of critical theory articulated by Max Horkheimer in the 1930s. My overall concern is to contribute to on-going efforts to decentre Frankfurt School critical theory in multiple dimensions. With the help of Horkheimer, I seek to show that this theoretical tradition has itself an important contribution to make to the endeavour. In Section 1, I argue that the methodology he advocates for critique of society offers a view of the relationship between the human mind and reality, as well as of humans with other humans, that avoids dogmatic rigidity and is hospitable towards mutual learning through engagement with other philosophical and cultural traditions. In Section 2, I consider the more specific challenge of anthropocentrism, suggesting the need for a more differentiated account of this. While critical theory is unavoidably anthropocentric in certain respects, it could avoid more pernicious forms of anthropocentrism that establish epistemic and ethical hierarchies between humans and other-than-human entities and that conceive of ethical validity as a purely human construction, with no independence of human needs and concerns.
Principal and Assistant Principal Involvement in and Barriers to Supporting Secondary Transition for Students with Disabilities
Authors: Brown Dottie , Plotner Anthony J. , Marshall Kathleen J.
Published: December 2023

To address disparities in post-school outcomes for students with disabilities, federal legislation mandates appropriate education programs to include transition planning and programs for students with disabilities. Because administrators are held responsible for ensuring appropriate educational programs for all learners including those with disabilities, it is important to understand their perspectives on secondary transition; however, research on administrators' involvement in secondary transition activities is limited. Using a single-state survey, this study examined the perspectives of secondary school administrators (i.e., principals and assistant principals) on their involvement and engagement in providing effective transition services for students with disabilities and their perceptions of barriers to providing and supporting transition efforts. Frequency of responses show the majority of administrators indicated they were highly involved in including parents and families in transition processes and attending IEP meetings. Yet, they were never directly involved with collaborating with community agencies to be actively involved with students with IEPs. Frequency of responses also show the majority of participants identified families not being prepared to participate in transition processes as a significant barrier as well as the absence of real-life instructional contexts (e.g., paid work experience) and lack of effective supports for students with IEPs from outside agencies as significant or moderate barriers. Implications for practice and future research are provided.
Memorizing song lyrics: Comparing the effectiveness of three learning formats
Authors: Napadow Miriam , Harmat László
Published: December 2023

A central part of singing includes learning new pieces of vocal music. Learning a new song is a complex task that involves several functions and modalities, such as memory functions, language and motor skills, and auditory and visual perception. Memory functions are a well-studied area, but it is unknown how memory theories apply to a multimodal activity such as singing. In this study, an attempt is made to translate the theories to the applied field of singing. This study aims to investigate the effectiveness of three types of learning formats for learning new song lyrics: auditory learning with image support (AI), auditory learning with text support (AT), and auditory learning only (A). Ninety-five participants were randomly assigned to one of the three experimental conditions. A univariate analysis of variance revealed a significant effect of condition on the lyric recall score and post-hoc tests showed that participants performed significantly better in the AI condition in comparison to both the AT and the A condition. No significant difference was found between AT and A. This study sheds light on how memory processes might work in learning song lyrics. Practical implications for practitioners such as music educators, conductors, and choir singers are discussed.
Immediacy, ensemble setup, and classroom space: A quasi-experimental study among secondary instrumental teachers and students
Authors: Roseth Nicholas
Published: December 2023

The purpose of this study was to examine the effect of closed and opened setup conditions on students’ and teachers’ reported immediacy, affect, motivation, and group cohesion in band and orchestra classrooms. A secondary purpose was to explore relationships among students’ and teachers’ reported immediacy, affect, motivation, and group cohesion. Six teachers and 379 of their students participated in the study. In this within-subjects experiment, teachers were asked to teach with their classrooms arranged in closed and opened setup conditions. In the closed condition, teachers used a traditional setup of arcs and were not asked to change their use of space when teaching. In the opened condition, an aisle was added to the ensemble setup and teachers were provided with strategies to encourage movement toward and among students when teaching. At the end of each condition, teachers and students completed measures of constructs related to immediacy, affect, motivation, and group cohesion. Results indicate the effect of the intervention increased negative affect among students, teacher proximity was associated with negative affect among students, and students’ perceptions of their teacher’s immediacy was found to have positive relationships with student affect, motivation, and group cohesion.
Stage Fright Scale – Children & Youth: Development and Validation of a New Questionnaire
Authors: Jaros Kamil , Gajda Aleksandra
Published: December 2023

Stage fright is a natural and very common phenomenon that affects everyone who must present themselves in public. However, it has a negative impact on the health and voice emission of children and adolescents, which is why it is important to study and measure it. Unfortunately, there are no appropriate tools for examining public presentation anxiety intended for children and adolescents, and that would also include the context of voice production. The main aim of this study was to describe stage fright and to present the stages of creating a tool based on the three-factor theory of stage fright constructs. The text describes the steps of developing the questionnaire, Confirmatory Factor Analysis, reliability, and convergent and discriminant validity. The results of the conducted analyses confirmed the three-factor structure of the tool and suggest that the Stage Fright Scale – Children & Youth is a reliable and consistent questionnaire for measuring stage fright in children and adolescents.
Oligarch Moralities of Wealth: The Russian Case
Authors: Schimpfössl Elisabeth
Published: December 2023

This article explores the dominant morality to which wealthy Russians adhered in their vision of how society should be organized and the role they see for themselves. The interviews with, and observations of, eighty Russian multi-millionaires and billionaires, their spouses, and their children, on which the article is based, were conducted from 2008 to 2017, a time when Russia’s rich were most settled in their positions. The interview analysis highlights the role of Soviet history and shows how it is integrated into, and harmonizes with, contemporary upper-class Russians’ notions of meritocracy. The author argues that drawing on international sociological research considerably advances our understanding of how Russian elites ideologically construe and morally legitimize the concentration of money and power in their own hands and how they model themselves as “good” in their actions and “deserving” of their fortunes. Conversely, the article suggests that these new findings on Russian elites (in particular, their references to their superior genes and their unwavering preference for private capital as a means to develop society—if necessary, to the detriment of democracy) offer great insights into, and have the potential to complement, established scholarship on Western elites (who emphasize hard work but tend to gloss over biology).
“Work Hard, Play Hard”: The Moral Economy of Company Celebrations in Post-Socialist Bulgaria
Authors: Bolgurova Rossitsa
Published: December 2023

This article explores shifts in workplace festivities in Bulgaria as part of the transition from socialism to post-socialism and analyses how work celebrations are used to express and uphold the moral economies informing them. During the socialist period, labour was glorified and work celebrations were a key instrument in the ideological and cultural engineering efforts of the state. Since the 1990s, private business owners have been reinterpreting and (re-)inventing festive traditions to stage their identities and moral orientations in discursive and performative ways. Based on in-depth interviews and participant observation in industrial production and high-tech companies from 2017 to 2019, I argue that highly mediated company celebrations are, in the wake of promotional cultures, an opportunity for employers to brand themselves as “good.” Such events also model the expectations of a “good employee,” for example, to be competitive not only regarding one’s work but also in having fun, as part of work, which is a reflection of the general insistence on happiness in the neoliberal workplace.
Caring for the Child, Caring for the Family: The Clash over the National Strategy for the Child (2019–2030) in Bulgaria
Authors: Nenova Gergana , Luleva Ana , Kotzeva Tatyana
Published: December 2023

The article explores the different meanings behind the narratives of “family,” “childcare,” and “child protection” in public discourses against the National Strategy for the Child (NSC) 2019–2030 in Bulgaria. These meanings are seen as reflecting the intertwining and cumulative effects of transnational and local influences in the anti-gender movement. Using frame analysis as an approach in social movement studies, the aim is to analyse the main ideas of NSC opponents—conservative far-right non-governmental organizations (NGOs) and citizens who joined the discussion during the public debate on the Strategy in January 2019. We differentiate between the discourses of the NGOs and the critical citizens, paying attention to the way they use the narrative of return—return to traditional family forms and child-rearing models. The conservative NGOs declared themselves to be defenders of Bulgarian children and families against the liberal policies of the European Union (EU) and the lesbian, gay, bisexual, and transgender (LGBT) lobbies. The citizens’ discourse is directed against the child-centred philosophy of the Strategy, seen as a threat to both the children themselves and parents’ rights, but it rarely mentions LGBT and gendering as a danger. The discussion revealed the deep distrust of citizens and parents towards the state and its institutions, which was amplified and instrumentalized by the far-right NGOs who mobilized and organized a mass social movement against the Strategy.
Resisting the Building Project of Whiteness: A Theological Reflection on Land Ownership in the Church of England
Authors: Walker Alison
Published: December 2023

Willie James Jennings contends that the goal of whiteness is the creation and preservation of segregated space. For Jennings, whiteness, as well as upholding perceived notions of white normativity, is a way of being in the world, an imagined reality made real by our movement in physical space which destroys the identity-forming connections between communities and land. In this article I bring together Pope Francis’s reflections on the globalised economy in Laudato Si’ with the critiques of James H. Cone and Jennings to demonstrate the horrific harm of whiteness on marginalised people groups and the land itself. To resist the building project of whiteness, therefore, requires attention to our relationship with land. At this point I turn more readily to the land of England, offering the beginnings of a theology of place given the substantial land holdings of the Church of England. I close by asking whether the Church of England can be trusted to use its land to dismantle whiteness given its troubling colonial history in relation to land use.
Anesthesia via peripheral nerve blocks during total knee replacement has no effect on postoperative inflammation in elderly patients
Authors: Lu Bin , Jin Jianwen , Pei Shujun , Gong Maowei , Liu Junle
Published: December 2023

Background

We have previously shown that, compared with general anesthesia (GA), the procedure of peripheral nerve blocks (PNB) facilitates faster recovery of elderly patients from total knee replacement (TKR). Here, we investigated whether the faster recovery is associated with decreased perioperative stress and inflammation and decreased incidences of postoperative complications.

Methods

After randomization, 165 patients aged ≥65 years underwent TKR under GA or PNB. The primary outcomes were the perioperative inflammation and stress levels, based on the serum C-reactive protein and interleukin-6 levels, erythrocyte sedimentation rate, white-blood cell and neutrophil counts, and blood-sugar level. The secondary outcomes were the postoperative complications, including cardiovascular, respiratory, and hepatic or renal complications, insomnia, delirium, electrolyte disturbances, and nausea and vomiting.

Results

The two groups were not significantly demographically different ( p > .05). Of the cytokines related to stress and inflammation, the differences of time points were statistically significant between the two groups ( p < .01), but two-way ANOVA revealed no interaction between the time points and groups. Incidences of postoperative complications were far lower in PNB group than in GA group ( p = .006). Incidences of postoperative respiratory complications ( p = .005) and postoperative nausea and vomiting ( p = .040) were significantly lower in PNB group than in GA group. There were no significant differences in other complications between the two groups ( p > .05).

Conclusions

PNB does not alleviate the stress and inflammation in elderly patients post TKR but significantly reduces the incidences of postoperative complications, especially respiratory complications, and nausea and vomiting. (ClinicalTrials.gov Identifier: NCT01871012)
Qualitative Systematic Literature Review: Participatory Visual Methods in Community Health Interventions With Migrants
Authors: Blohm Frederikke Sissel , Jacobsen Marie Honoré , Villadsen Sarah Fredsted , Sandholdt Catharina Thiel
Published: December 2023

This systematic review investigates how participatory visual methods (PVMs) (1) are applied in community health interventions (CHIs) with adult migrant populations and (2) identify potentials for participation. The search was performed in PubMed in 2021 and 2023. Eighteen articles fulfilled inclusion criteria as they investigated a CHI targeting migrants and used a visual method. We excluded articles that used quantitative methods, articles written in languages other than English, Danish, Swedish, or Norwegian, and the formats reviews, protocols, and theoretical articles. As a framework to graduate the degree of participation, we applied Arnstein’s ‘A Ladder of Citizen Participation’. Most of the studies took place in the United States, and the most frequent method used was photovoice. We categorize an equal number of articles as ‘degrees of citizen power’ or ‘degrees of tokenism’. We identify the capacity to accommodate the needs of specific target groups to be a strength in PVMs, which has potential to engage migrants in several parts of the research process. Additionally, PVMs can be used to support a change in the participants’ lives by facilitating a reflexive process concerning their life situation. However, utilization of PVMs also include a risk of tensions, they can be resource-demanding and potentially exclude certain groups.
Experiences of Fathers in Norway Attending an Online Course on Therapeutic Writing After the Death of a Child
Authors: Lehmann Olga V. , Kalstad Trine Giving , Neimeyer Robert A.
Published: December 2023

After the unexpected death of a child, bereaved parents require prompt access to helpful support systems. Online therapeutic writing courses can make such support accessible. Because few studies have included bereaved fathers as participants, we explored the experiences of fathers whose children died unexpectedly and who were part of an online course of therapeutic writing in Norway. We piloted two courses (group 1, six weeks, n = 9; group 2, 5 weeks, n = 5). We describe our methodological considerations for using poetic representations in qualitative health research and present four poetic representations based on fieldwork notes written by the principal investigator. Then, we triangulate and narratively analyze them together with two collective poems written by participants from each group; excerpts of the writings from two fathers, one per group; evaluation surveys ( n = 4; n = 3); and, anonymous check-out journaling from the second group ( n = 3). Resistance was a salient feature of our participants’ grief, and writing enabled them to both be in contact with their emotional world and process difficult emotions as they looked for meaning despite the death of their children. Those who attended the most classes perceived the course as transformative, being part of an ongoing self-exploration, and a possibility to continue and strengthen the bond with their children. Our findings mirror the complexities of the grief experiences of fathers, giving account of their need to find a rhythm to dive into their emotional world, the importance of peer support, and the value of diversifying intervention techniques to meet individual needs and preferences.
Optimization design and analysis of the broadband acoustic absorber of the microperforated panel with an interpolated straight tube
Authors: Li Qi , Wu Jinwu , Mao Qibo , Jv Xin , Chen Minghao
Published: December 2023

The microperforated panel (MPP) structure is widely used in the field of noise reduction. The traditional MPP structure has a fixed absorption peak, and the optimized MPP structure has an improved absorption band, but the frequency range of the absorption is not ideal. For the design of broadband absorption in MPP structures, this paper presents a MPP acoustic absorber structure (N-MH) with an interpolated straight tube (IST) designed for superior broadband acoustic performance. The N-MH structure combines the advantages of the MPP and the embedded necked Helmholtz resonator, as well as having a sub-wavelength thickness of only 60 mm, which is only 1/14th of the wavelength at the first resonant frequency. The N-MH structure is optimized based on the particle swarm optimization (PSO) algorithm. In comparison to traditional microperforated panel structures, the N-MH structure exhibits a significantly broader sound absorption frequency band. Additionally, we thoroughly investigate the factors influencing the mid-low-frequency sound absorption performance of the N-MH structure. Through theoretical prediction, simulation analysis, and experimental testing, it is verified that the N-MH structure has excellent broadband sound absorption characteristics in the frequency interval of 0–2000 Hz, and the percentage of sound absorption bands with absorption coefficients exceeding 0.9 can reach 78.2%.
How do strategic pricing approaches influence franchise fee decisions?
Authors: Sun Kyung-A , Lee Seoki
Published: December 2023

In the franchising market, transactions involve franchisees paying franchisors for the right to use their business models. In such transactions, the franchise fee functions as the transaction price, which is a critical component of profitability and the long-term survival of franchise brands. Based on Ohmae’s 3Cs (i.e., cost, competition, and customers) model, this study investigates how strategic pricing approaches influence franchise fees. The empirical results suggest that franchise fees are influenced by the cost-based and the value-based approaches but not by the competition-based approach. Furthermore, among the approaches, the cost-based approach is found to have the greatest impact on the franchise fee, followed by the value-based and the competition-based approaches, respectively. Additional analysis found that the different pricing approaches are used depending on the business characteristics. By delineating the pricing mechanism of the franchise fee, these findings contribute to the literature on franchising in the hospitality industry, strategic management, and marketing and have important implications for industry practitioners.
In search of decolonised political futures: Engaging Mahmood Mamdani's neither settler nor native
Authors: Moradi Fazil
Published: December 2023

This text offers a brief overview of the Special Issue on Mahmood Mamdani's book, Neither Settler Nor Native: The Making and Unmaking of Permanent Minorities (2020), and a reading of the contributions and of Mamdani's plea for the historic importance of epistemological revolution and of learning to imagine a community of survivors. My reading is mediated through an autobiographical critique of political modernity and ongoing state violence. I explore more deeply what Mamdani calls ‘settler autobiography’ and a community of survivors, other than a community of memory that is unified and homogenised. By turning to unauthorised autobiographies, the autobiographies of those subjected to colonialism as annihilatory violence, I take up Mamdani's call to rethink political violence and the possibility of living together as survivors in Iran as a ‘decolonised political community’. In order to do so I turn to memories of irredeemable destruction, displacement and incalculable losses that live on in our (my mother's and my) deferred autobiographies, alongside the epistemological revolution in Iran—Women. Life. Freedom.
Study on the friction characteristics of the bonding point of variable cross-section three-dimensional braided yarn increase based on the bonding method
Authors: Cheng Pan , He Xinhai , Zhou Hao , Liu Fei , Liang Junhao , Wei Yubo , Li Yanzhang
Published: December 2023

In the process of using adhesive method for variable cross-section 3D weaving, the introduction of adhesive at the yarn increasing point greatly increases the friction and wear between carbon fibers, which can lead to a decrease in the overall performance of the prefabricated component. In response to the above issues, a self-made experimental fixture was developed to test the friction and wear performance between carbon fibers in bonding process. The effects of friction angle, preloaded tension, and friction frequency on the friction properties between carbon fiber bundles were investigated. Solidworks is used to model bonded carbon fiber bundles with a friction angle of 90°, and ABAQUS is used to simulate the friction of the bonded carbon fiber bundle. The experimental results show that stress concentration occurs in the center of the friction area, and the wear degree at the center is more obvious, and the number of fiber breaks at the center was more than that of the side. Friction angle has great influence on friction coefficient, while pre-tensioning and friction frequency had a negligible effect. Based on the above results, when performing variable cross-section 3D weaving, it is recommended to increase the spacing between adjacent carriers and shorten the distance between the weaving chassis and the prefabricated parts. Additionally, it is advised to reduce the pre-added tension on the carrier device and increase the knitting frequency as much as possible within the scope of working conditions. The study results are of great significance for developing 3D weaving devices in terms of theoretical and engineering guidance.
Intellectual Disability and Epilepsy: The High Incidence and the Risks of Status Epilepticus and Sudden Death Require Improved Therapies
Authors: Vossler David G.
Published: December 2023

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The lost art of joy in early childhood education
Authors: Little Cathy , Karaolis Olivia
Published: December 2023

Early childhood education is a sector often mis-represented in the media and public domain, depicting a sector beleaguered by low salaries, lack of professional recognition and inadequate working conditions. Missing from this depiction is the fullness of the everyday teaching and learning experiences of early childhood educators, and subsequent joy experienced in working with young children and families and the significant contribution of this emotion to educator practice and sense of wellbeing. Using an online survey, educators were invited to share their perspectives of factors that are contributing to the crisis in the field, their daily encounters with children and the moments, both big and small, that shaped and guided their pedagogy. Findings suggested that while the concept of joy was embraced and validated by educators, it was also elusive and hard to define. Suggestions for validating the place of joy as central in early childhood education conclude the paper.
Monocultural crises and rural geographies
Authors: Williams Brian
Published: December 2023

This commentary engages with Wang et al.'s formulation of planetary rural geographies through the global agro-industrial complex. Focusing on the violent roots, unequal drivers, and differentiated dynamics of agroindustrial development, I emphasize that agro-industrial expansion and intensification often carries forward technological and territorial legacies of plantations, colonialism, and warfare against rural places and people. A focus on monocultural developments as racial-colonial projects of control and extraction, I argue, is critical to understanding the contemporary dynamics of rural crises.
Barriers and facilitators that hospital clinicians perceive to discuss the personal values, wishes, and needs of patients in palliative care: a mixed-methods systematic review
Authors: de Vries Sita , Verhoef Mary-Joanne , Vervoort Sigrid Cornelia Johanna Maria , van der Linden Yvette Milene , Teunissen Saskia Cornelia Constantia Maria , de Graaf Everlien
Published: December 2023

Background:

The exploration and monitoring of the personal values, wishes, and needs (VWN) of patients in the palliative phase by hospital clinicians is essential for guiding appropriate palliative care.

Objective:

To explore the barriers and facilitators concerning communication with patients in the palliative phase about their VWN as perceived by hospital clinicians.

Design:

A mixed-methods systematic review following the Joanna Briggs Institute guidelines for mixed-method systematic reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted (PROSPERO ID: CRD42021216693).

Data sources and methods:

Eight databases, including PubMed, Embase, and CINAHL, were searched without time restrictions. The search string was built using the search Palliative cAre Literature rEview iTeraTive mEthod (PALETTE) framework. Eligible studies focused on (1) hospital clinicians and (2) perceived barriers and facilitators regarding the exploration and monitoring of the VWN of adult patients in the palliative phase. Two researchers independently selected articles and evaluated the quality. Findings were synthesized using a convergent integrated approach.

Results:

In total, 29 studies were included: 14 quantitative, 13 qualitative, and 2 mixed methods. Five synthesized findings were identified: (1) the clinician’s professional manners, (2) the image formed of the patient and loved ones, (3) the human aspect of being a clinician, (4) the multidisciplinary collaboration, and (5) the contextual preconditions. Most studies seemed focused on communication about treatment decision making.

Conclusion:

A patient-centered approach seems lacking when clinicians discuss the patient’s VWN, since most studies focused on treatment decision making rather than on the exploration and monitoring of the multidimensional well-being of patients. This review emphasizes the need for the development and integration of a systematic approach to explore and monitor the patients’ VWN to improve appropriate palliative care in hospitals.
Targeting Libya’s rentier economy: The politics of energy, water, and infrastructural decay
Authors: Weinthal Erika , Sowers Jeannie
Published: December 2023

Libya’s fossil fuel wealth has dominated its political economy and state institutions since the 1960s and paid for large-scale, centralized water and energy infrastructures. Since the 2011 revolution, these infrastructures have been at the center of Libya’s protracted conflict. Unlike other protracted conflicts in the Middle East and North Africa in which water and energy were directly and extensively targeted, we find that warring parties in Libya have largely not sought to destroy but rather control and disrupt Libya’s rentier state institutions. The oil and gas infrastructure, along with the National Oil Company and the central bank that processes oil revenues, are at the heart of elite rivalries over political authority. We find relatively infrequent attacks on centralized water infrastructures. The toll of protracted conflict on water-energy systems has been cumulative, with looting, lack of repair and investment, and departure of qualified personnel. We draw upon an original dataset, qualitative interviews with humanitarian actors, policymakers, and Libyan experts, and a review of extant literature to show how and when local communities, armed militias, former army units, and aspiring warlords sought to capture and leverage water and energy infrastructures. The article highlights the consequences of infrastructure targeting for broader human security.
Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Induction and Consolidation with Tandem Transplant in High-Risk Newly Diagnosed Myeloma Patients: Final Results of the Phase 2 Study IFM 2018-04
Authors: Touzeau Cyrille , Perrot Aurore , Hulin Cyrille , Manier Salomon , Macro Margaret , Chretien Marie-Lorraine , Karlin Lionel , Decaux Olivier , Jacquet Caroline , Tiab Mourad , Leleu Xavier , Corre Jill , Jobert Alexandra , Planche Lucie , Avet-Loiseau Herve , Moreau Philippe
Published: December 2023

Background: High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with favorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improved response rate and progression free-survival in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improved outcome of HR TE NDMM patients (EMN02). The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) evaluated an intensive strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577).

Methods: HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Treatment strategy included Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance for 2 years. The primary endpoint was the feasibility of this intensive strategy.

Results: Fifty patients with previously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers. Median age was 57 (range 38 -65). Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10, 20%). Four (8%) patients had extramedullary disease. At data cut-off, the study met the primary endpoint with 36 (72%) patients completing second transplant. Twenty-one patients (42%) discontinued the study, due to stem-cell collection failure (n=8), disease progression (n=8), adverse event (n=4), consent withdrawal (n=1). Grade 3-4 Dara-KRD induction/consolidation related adverse event (>5% of patients) were neutropenia (44%), anemia (22%), thrombocytopenia (24%) and infection (14%). Four patients discontinued treatment due to severe adverse event (COVID-19 infection, drug-induced hepatitis, JC virus related encephalopathy, intracerebral hemorrhage). Seven patients died, 5 due to disease progression and 2 due to infection. Responses deepened over time with an overall response rate before maintenance of 100%, including 81 % complete response. Among evaluable patients (33/36), pre maintenance Minimal Residual Disease negativity rate (NGS, 10 -6) was 94%. After a median follow up of 32 months, the 24-months PFS is 87% (78-87%) and the 24-months OS is 94% (87-100%).

Conclusions: Dara-KRD induction/consolidation with tandem transplant was feasible in TE NDMM patients with high-risk cytogenetic profile, and resulted in high MRD negativity rate and high progression free survival.
CFT8634, a Clinical Stage BRD9 Bi DAC™ Degrader, Is Active in a Subset of Multiple Myeloma Cell Line Models and Synergistic When Combined with Pomalidomide
Authors: Poling Laura L , Cocozziello David , He Minsheng , Hurh Eunju , Lobbardi Riadh , Jackson Katrina L , Fisher Stewart L , Pollock Roy M
Published: December 2023

Recent literature has shown that loss-of-function of BRD9, a component of the noncanonical SWI/SNF (ncSWI/SNF) complex, mediated either by RNA interference or by BRD9 tool degrader compounds can inhibit multiple myeloma (MM) cell lines and primary MM cell proliferation in vitro, as well as inhibit mouse MM xenograft tumor growth in vivo. Additionally, in vitro synergy in MM proliferation assays was observed when a tool BRD9 degrader was combined with the standard of care (SoC) agents, dexamethasone or pomalidomide. Given the continued unmet need of the MM patient population, we explored the therapeutic potential of CFT8634 in this indication. CFT8634, a potent and selective oral BiDAC™ degrader of BRD9, is currently in a Phase 1/2 clinical trial (NCT05355753) for the treatment of SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors. Pharmacokinetic and pharmacodynamic data to date from the ongoing trial of CFT8634 has demonstrated dose-proportional human plasma exposure and robust BRD9 degradation in patient tumor samples thereby establishing proof of mechanism in patients.

Here we show that CFT8634 has anti-proliferative activity in a subset of MM cell lines that translates into tumor growth inhibition in MM xenograft models at clinically relevant CFT8634 exposures. We observe that cell lines less sensitive to pomalidomide tend to be significantly more sensitive to CFT8634 treatment. As pomalidomide is a SoC treatment in MM, we interrogated the ability to combine CFT8634 and pomalidomide. CFT8634 demonstrates synergy with pomalidomide in MM cell lines where CFT8634 is anti-proliferative as a single agent. We further show that clinically relevant exposures of CFT8634 demonstrate synergy with pomalidomide in vivo in the NCI-H929 mouse xenograft model (Figure 1). This model is relatively unresponsive to pomalidomide alone, suggesting that CFT8634 can render otherwise recalcitrant MM tumors sensitive to the effects of pomalidomide in combination. Pharmacokinetic and pharmacodynamic analyses show that in combination, CFT8634 and pomalidomide do not interfere with the ability to degrade each other's targets (BRD9 and IKZF1/3, respectively) despite both utilizing the E3 ligase cereblon.

In conclusion, we demonstrate in vitro and in vivo activity in an expanded set of MM models using the clinical oral BRD9 degrader CFT8634 as a single agent and show in vivo synergy between CFT8634 and pomalidomide at clinically relevant doses. Our findings suggest that combining CFT8634 with pomalidomide may be a viable therapeutic strategy in treating MM patients.
Multiplex Genome Editing of Human T Cells with Innovative Transformer Base Editor (tBE) for Construction of Next Generation CAR-T Therapies
Authors: Li Peixue , Su Qing , Xu Ya , He Jing , Wang Lijie , Wang Yichuan , Li Huanyu , Lan Kewei , Zheng Huiming , Zhu Di , Zhang Yan , Guo Runni , Ma Hongxia , Zhang Lang , Zhang Yuchen , Gao Runze , Wu Bingbing , Mou Susan , Chen Jia
Published: December 2023

Autologous chimeric antigen receptor T (CAR-T) cell therapy has achieved great success for antitumor treatments especially against hematological malignancies, and several autologous CAR-T therapies have been approved around the world. However, high manufacturing cost and long manufacturing process hinder the broader application of autologous CAR-T cell therapy. As a result, off-the-shelf universal CAR-T cell therapy with donor derived healthy T cells is of great interest and under development by many companies globally. Gene editing technologies including TALENs, CRISPR/Cas nucleases and base editors are of great potential in T cell engineering for allogeneic T cell therapy. The innovative transformer base editor (tBE) is a base editing system that avoids to cause DNA double strand breaks (DSBs) and exhibits higher editing efficiency, no detected off-target mutations and lower cytotoxicity. Due to its capability to avoid off-target mutations and DSB-caused chromosomal translocations, tBE is potentially one of the best gene editing tools to induce multiplex editing in cells. Here we show that the tBE was used to induce highly efficient single or multiplex gene editing in primary human T cells. With optimized electroporation conditions for tBE, TRAC, CD52 and PDCD1 could be knocked out simultaneously with editing efficiency up to ~90% for each target gene. tBE triggered no detected off-target mutation or chromosomal abnormalities, which were reported in the cases of CRISPR/Cas- or TALEN-mediated multiplex editing. CD19-targeted CAR-T cells with triplex base editing exhibits enhanced antitumor efficacy in vitro and in mouse models compared with unedited CAR-T cells. Our results demonstrated the application of tBE for construction of next generation universal or enhanced CAR-T therapies.
Preliminary Results from a Phase I/II Study of Pomalidomide Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (PRIDE)
Authors: Xu Pengpeng , Li Wang , Cheng Shu , Zhao Wei Li
Published: December 2023

Background: Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients have limited treatment options and are associated with poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. The addition of the immunomodulatory agent lenalidomide (Len) to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in some studies. Pomalidomide (Pom) is a third-generation immunomodulatory drug that has shown excellent therapeutic activity against relapsed/refractory primary central nervous system lymphoma (PCNSL) with an acceptable toxicity profile. We conducted a phase I/II study combining Pom with RICE (PRICE) as a salvage regimen in first-relapse or primary refractory DLBCL (ChiCTR2100049327). Here we report the phase I results of the study.

Methods: In phase I of the study, patients receive escalating doses of pomalidomide (2 mg, 3 mg, or 4 mg daily on d1-10) along with R-ICE therapy every 21 days by 3+3 design. Patients with CR or PR but not eligible for ASCT receive continuous pomalidomide as maintenance therapy for 12 months. The primary objective was to determine the maximum tolerated dose (MTD) or recommended dose, based on the occurrence of treatment-related DLTs. Secondary objectives included tumor response and safety.

Results: At data cut-off (July 11, 2023), 14 patients were screened and 10 eligible patients were enrolled. 9 patients had been treated in the first 2 dose-escalation cohorts: 6 patients at 2 mg and 6 patients at 3 mg. Patient characteristics at baseline are shown in Table I. DLT was observed in two patients in the 3 mg cohort (grade 4 thrombocytopenia and grade 4 rash). MTD was determined as 2 mg. Grade (G) ≥ 3 TRAEs were leukopenia (4 patients), lymphopenia (3 patients), thrombocytopenia (3 patients), neutropenia (3 patients), rash (1 patient) and myelosuppression (1 patient). No death was related to the treatment. Five patients (55.6%) achieved an objective response including four patients (44.4%) with CR. ORR for the MTD dose level was (4/6) 66.7% with 3 CR and 1 PR. Notably, among the 7 patients with MYD88 mutations, which are associated with enhanced NF-κB activity, 4 achieved CR and 1 achieved PR.

Conclusion: The addition of pomalidomide to the widely used RICE salvage regimen is feasible, and results in promising response rates in this DLBCL population that mostly with non-GCB subtype and double expression. MTD was reached and RP2D was determined to be 2 mg. Further studies are needed to evaluate the efficacy of this regimen, particularly in patients with MYD88 mutations.
Using infrared cameras in drones to detect bleeding events
Authors: West Christoph , Kaus Bernhard , Sullivan Sean O’ , Schneider Henning , Seifert Oskar
Published: December 2023

Background

Hemorrhage is one of the main causes of death in trauma. Critical bleeding in patients needs to be detected as soon as possible to save the patient. Drones are gaining increasing importance in emergency services and can support rescue forces in accident scenarios such as a mass casualty incident.

Methods

In this study, a simulated pelvic hemorrhage was detected using a drone from 7 m above the ground over a time span of 30 s.

Results

The results allow a good detection of the pelvic hemorrhage. Nevertheless, the simulated blood cools down quickly. After 30 s, there was no significant temperature difference compared to the rest of the body. At this point, further assessment is only possible via the RGB image.

Conclusion

The findings suggest that bleeding from an open and continuously bleeding wound would most likely be detectable using the drone’s thermal imaging camera, even over a longer period of time.
Association between gestational exposure and risk of orofacial clefts: a systematic review and meta-analysis
Authors: Huang ZhiMeng , Wu JinZhun , Qiu Yue , Lin Jiayan , Huang Wanting , Ma Xiaohui , Zhang Huifen , Yang Xiaoqing
Published: December 2023

Background

The occurrence of orofacial Clefts (OFCs) is a congenital disease caused by many factors. According to recent studies, air pollution has a strong correlation with the occurrence of OFCs. However, there are still some controversies about the current research results, and there is no relevant research to review the latest results in recent years.

Objective

In this paper, the authors conducted a systematic review and meta-analysis to explore the correlation between ambient air pollution and the occurrence of neonatal OFCs deformity.

Methods

We searched Pubmed, Web of science, and Embase databases from the establishment of the database to May 2023. We included observational studies on the relationship between prenatal exposure to fine particulate matter 2.5 (PM2.5), fine particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO) and the risk of cleft lip (CL), cleft palate (CP), cleft lip with or without palate (CL/P). the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the literature. Funnel plot and Egger’s regression were used to verify the publication bias. Random effect model or fixed effect model was used to estimate the combined relative risk (RR) and 95% confidence interval (95%CI).

Results

A total of eleven studies were included in this study, including four cohort studies and seven case-control studies, including 22,453 cases of OFCs. Ten studies had low risk of bias and only one study had high risk of bias. Three studies reported that PM2.5 was positively correlated with CL and CP, with a combined RR and 95%CI of 1.287(1.174,1.411) and 1.267 (1.105,1.454). Two studies reported a positive correlation between O3 and CL, with a combined RR and 95%CI of 1.132(1.047,1.225). Two studies reported a positive correlation between PM10 and CL, with a combined RR and 95%CI of 1.108 (1.017,1.206). No association was found between SO2, CO, NO2 exposure during pregnancy and the risk of OFCs.

Conclusion

The results of this study showed that there was a significant statistical correlation between exposure to PM10, PM2.5, O3 and the risk of OFCs in the second month of pregnancy. Exposure assessment, research methods and mechanisms need to be further explored.