bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer
Authors: Cui Luying , Liu Ruiqi , Han Shuling , Zhang Chunhui , Wang Bojun , Ruan Yuli , Yu Xuefan , Li Yien , Yao Yuanfei , Guan Xin , Liao Yuanyu , Su Dan , Ma Yue , Li Shuijie , Liu Chao , Zhang Yanqiao
Published: December 2024

ARID1A, a core constituent of SWI/SNF complex, is mutated in approximately 10% of colorectal cancers (CRC). While ARID1A deficiency corresponds to heightened immune activity in CRC, immune checkpoint inhibitors (ICIs) have shown limited efficacy in these tumors. The discovery of targetable vulnerabilities associated with ARID1A deficiency in CRC could expand treatment options for patients. In this study, we demonstrated that arachidonic acid metabolism inhibitors synergize with ICIs in ARID1A-deficient CRC by enhancing the activity of CD8+ T cells and inhibiting vasculogenic mimicry (VM). Epigenetic analysis using ATAC-seq and ChIP-qPCR revealed that the lack of ARID1A results in reduced levels of PTGS1 and PTGS2, the key enzymes that control the arachidonic acid pathway. Low PTGS1 and PTGS2 expression generated a reliance on the remaining functionality of the arachidonic acid pathway in ARID1A-deficient cells. The arachidonic acid pathway inhibitor aspirin selectively inhibited the growth of ARID1A-deficient CRC, and aspirin sensitized tumors lacking ARID1A to immunotherapy. Together, these findings suggest that blocking arachidonic acid metabolism can enhance immune responses against tumors by activating CD8+ T cells and inhibiting VM, which synergizes with ICIs to improve treatment of ARID1A-deficient CRC.
Multiomics Reveals the Immunologic Features and the Immune Checkpoint Blockade Potential of Colorectal Medullary Carcinoma
Authors: Liu Chao , Zou Haoyi , Ruan Yuli , Fang Lin , Wang Bojun , Cui Luying , Wu Tong , Chen Zhuo , Dang Tianjiao , Lan Ya , Zhao Wenyuan , Zhang Chunhui , Meng Hongxue , Zhang Yanqiao
Published: December 2024

Purpose:

Colorectal medullary carcinoma (MeC) is extensive lymphocyte infiltration and is associated with an active immune response. However, studies to comprehensively explore the immune landscape and efficacy of immune checkpoint blockade (ICB) therapy in MeC are limited.

Experimental Design:

We screened 47 cases of MeC from the Harbin Medical University Cancer Hospital cohort. The immunologic characteristics of MeC were analyzed by targeted exon sequencing, NanoString nCounter gene expression sequencing, IHC, multiplexed immunofluorescence, and T-cell antigen receptor sequencing. An additional 47 patients with MeC who received ICB therapy were included in the retrospective analysis to verify the efficacy of immunotherapy.

Results:

Genomically, MeC tends to have a higher proportion of mismatch repair protein deficiency/microsatellite instability (MSI), ARID1A mutation, and ASCL2 amplification. Gene expression shows enriched immune response–related pathways while downregulating oncogenic pathways, such as glycolysis, epithelial–mesenchymal transition, and Wnt/β-catenin signaling. Further immune characterization showed that MeC showed advantages in antigen presentation, co-stimulatory molecules, effector molecules, immune checkpoints, and immune cell abundance. More importantly, both MSI and microsatellite-stable type MeC showed a similar state of high infiltration of immune cells, even better than MSI non-MeC. MeC infiltrated massive highly clonal immune cells, especially intraepithelial CD8+ T cells. In the retrospective cohort, there were 30 patients with MeC who received ICB therapy and achieved complete or partial response with an objective response rate of 63.8%, especially including 16 patients with microsatellite-stable colorectal cancer.

Conclusions:

MeC is a pathologic subtype with an active immune response and is a promising group for ICB therapy. This heightened immune response was not limited to the patients' microsatellite status.
Abstract IA014: Mechanistic insights for the advancement of PPARG inverse agonists in muscle invasive urothelial cancer
Authors: Stuckey Jacob I. , Mertz Jennifer , Wilson Jonathan , Li Yong , Chenail Gregg , Kuljanin Miljan , Audia James , Sims Robert
Published: December 2024

In the last decade, genetic activation of PPARG in muscle invasive urothelial cancer (MIUC) has emerged as a potential therapeutic intervention point. More than two decades ago, the first PPARG covalent inverse agonist was described. While cellularly potent, subsequent drug discovery efforts to understand and improve the pharmacology of this initial inverse agonist were largely unsuccessful until quite recently. We have recently disclosed FX-909, a covalent inverse agonist of PPARG that shows durable tumor regressions in PPARG-activated xenograft models. Detailed structural, biochemical and medicinal chemistry studies were critical to both rational and rapid evolution from previously described covalent PPARG inverse agonists to FX-909, which exhibits both superior pharmacological and in vivo properties. Mechanistic understanding of the altered conformational landscape of PPARG in MIUC integrated with detailed insights into the covalent reaction coordinate of PPARG inverse agonists enabled the design of FX-909, specifically tailored to exhibit robust “conformational biasing” that counters the PPARG conformational “activation bias” observed in MIUC.

Citation Format: Jacob I. Stuckey, Jennifer Mertz, Jonathan Wilson, Yong Li, Gregg Chenail, Miljan Kuljanin, James Audia, Robert Sims. Mechanistic insights for the advancement of PPARG inverse agonists in muscle invasive urothelial cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA014.
Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Authors: Chesner Lisa N. , Polesso Fanny , Graff Julie N. , Hawley Jessica E. , Smith Alexis K. , Lundberg Arian , Das Rajdeep , Shenoy Tanushree , Sjöström Martin , Zhao Faming , Hu Ya-Mei , Linder Simon , Chen William S. , Hawkins Reed M. , Shrestha Raunak , Zhu Xiaolin , Foye Adam , Li Haolong , Kim Lisa M. , Bhalla Megha , O’loughlin Thomas , Kuzuoglu-Ozturk Duygu , Hua Junjie T. , Badura Michelle L. , Wilkinson Scott , Trostel Shana Y. , Bergman Andries M. , Ruggero Davide , Drake Charles G. , Sowalsky Adam G. , Fong Lawrence , Cooperberg Matthew R. , Zwart Wilbert , Guan Xiangnan , Ashworth Alan , Xia Zheng , Quigley David A. , Gilbert Luke A. , Feng Felix Y. , Moran Amy E.
Published: December 2024

Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression. To uncover the mechanism, we performed a genome-wide CRISPR interference (CRISPRi) screen and identified androgen receptor (AR) as a repressor of the MHCI pathway. Syngeneic mouse models of aggressive prostate cancer deficient in Ar also demonstrated increased tumor immunogenicity and promoted T cell–mediated tumor control. Notably, the increase in MHCI expression upon AR blockade is transient and correlates with resistance to AR inhibition. Mechanistic studies identified androgen response elements upstream of MHCI transcription start sites which increased MHCI expression when deleted. Together, this body of work highlights another mechanism by which hormones can promote immune escape.

Significance:

Immunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients.
First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: December 2024

Purpose:

In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.

Patients and Methods:

Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.

Results:

Twenty-eight participants were enrolled across seven cohorts and received a median of four cycles of 23ME-00610. No treatment-related serious adverse events (AE) were observed, and the maximum tolerated dose was not reached. Overall, the PK of 23ME-00610 was linear and dose proportional for doses ≥60 mg, with a median terminal half-life of 13 days at 1,400 mg. Peripheral saturation of CD200R1 was observed for doses ≥60 mg. Immune-related AEs, including rash, pruritus, and hypothyroidism, were predicted by phenome-wide association studies and observed for doses ≥60 mg. A confirmed partial response was observed in a participant with well-differentiated pancreatic neuroendocrine cancer whose tumor was among those with the highest tumor CD200 expression.

Conclusions:

23ME-00610 has mild-to-moderate on-target AEs and PK/PD consistent with tumor target saturation and dosing every 3 weeks. The trend for clinical benefit in participants with tumor CD200 expression suggests that 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary antitumor activity, 1,400 mg Q3W was selected as the dose for further study.

Significance:

Genome-wide association studies (GWAS) of the 23andMe genetic database identified CD200R1 as a promising therapeutic target for cancer. This phase 1 study of 23ME-00610, a CD200R1 antagonist IgG1, showed acceptable safety and tolerability, PK supporting Q3W dosing, and PD and preliminary clinical activity supporting an initial recommended phase 2 dose of 1,400 mg.
Relationship between Anxiety Concerning Dementia Onset and Subjective Memory Impairment in Frail Older Individuals
Authors: Suzuki Yukiko , Sudo Takayuki , Mochizuki Hideki , Shimoda Nobuaki
Published: December 2024

Introduction: This study aimed to clarify the relationship between anxiety about the possibility of developing dementia (dementia onset anxiety) and subjective memory impairment in frail older individuals who require long-term care and are experiencing declining cognitive function. Methods: This study included 30 frail older individuals requiring long-term care who completed the Everyday Memory Checklist (EMC), which was simultaneously performed by an occupational therapist (OT). Individuals were divided into two groups: with and without anxiety about dementia onset. We examined the relationship between the presence of anxiety about dementia onset and assessment scores on EMC by the individuals and by the OT. Results: Approximately 40% of participants expressed anxiety about developing dementia. No significant differences existed between the two groups in terms of age, sex, number of years of education, number of ongoing medical conditions under treatment, types of oral medications, Mini-Mental State-Japanese scores, and total functional independence measure scores. Self-assessed EMC scores by the individuals showed a significant difference between the two groups (p = 0.012, φ = 0.41), while no significant difference in the OT-assessed EMC scores. Conclusion: Despite similar levels of objective cognitive decline and objective everyday memory impairment, individuals with anxiety about developing dementia have more severe subjective memory impairment than those without such anxiety.
Burden of Cardio-Cerebrovascular and Renal Diseases Attributable to Systolic Hypertension in France in 2021
Authors: Grave Clémence , Bonaldi Christophe , Carcaillon-Bentata Laure , Gabet Amélie , Halimi Jean-Michel , Tzourio Christophe , Béjot Yannick , Torres Marion J. , Steg Philippe Gabriel , Durand Zaleski Isabelle , Blacher Jacques , Olié Valérie
Published: December 2024

BACKGROUND:

Hypertension is the most common chronic disease and a major modifiable risk factor for cardio-cerebrovascular and renal diseases. This study estimated the national burden of hypertension, defined as systolic blood pressure ≥140 mm Hg, on morbidity and mortality in 2021 in France.

METHODS:

For all diseases causally associated with hypertension (cardiovascular diseases, chronic kidney diseases, and dementia), the number and proportion of cases attributable to hypertension in adults aged ≥35 years were estimated using population attributable fractions. Age- and sex-specific population attributable fractions were computed using the distribution of hypertension in the French population. These population attributable fractions were applied to nationwide statistics for mortality, hospitalizations, disease prevalence, years of life lost, years of life lived with disability, and disability-adjusted years of life.

RESULTS:

The largest population attributable fractions were for ischemic heart disease and hemorrhagic stroke, with over 40% of cases attributable to hypertension. Overall, more than 385 000 patients were hospitalized due to hypertension, with 3.7 million hospitalizations and 6.2 million hospital days (all hospitalizations, including 3.4 million for chronic kidney disease) and including 390 000 overnight hospitalization. In 2021, more than 1.15 million individuals lived with ischemic heart disease attributable to hypertension, 1.26 million with chronic kidney diseases, and 358 033 with heart failure. Among 184 059 annual deaths from cardiovascular diseases, dementia, and chronic kidney diseases, 30% (55 280 deaths) were attributable to hypertension. Hypertension accounted for 8.5% of all deaths and 498 052 years of life lost.

CONCLUSIONS:

In France, despite near-universal health coverage and free health care access, the burden attributable to hypertension remains high.
Real-time computation of brain E-field for enhanced transcranial magnetic stimulation neuronavigation and optimization
Authors: Hasan Nahian I. , Dannhauer Moritz , Wang Dezhi , Deng Zhi-De , Gomez Luis J.
Published: December 2024

Transcranial Magnetic Stimulation (TMS) coil placement and pulse waveform current are often chosen to achieve a specified E-field dose on targeted brain regions. TMS neuronavigation could be improved by including real-time accurate distributions of the E-field dose on the cortex. We introduce a method and develop software for computing brain E-field distributions in real-time enabling easy integration into neuronavigation and with the same accuracy as 1st-order finite element method (FEM) solvers. Initially, a spanning basis set (<400) of E-fields generated by white noise magnetic currents on a surface separating the head and permissible coil placements are orthogonalized to generate the modes. Subsequently, Reciprocity and Huygens’ principles are utilized to compute fields induced by the modes on a surface separating the head and coil by FEM, which are used in conjunction with online (real-time) computed primary fields on the separating surface to evaluate the mode expansion. We conducted a comparative analysis of E-fields computed by FEM and in real-time for eight subjects, utilizing two head model types (SimNIBS’s ‘headreco’ and ‘mri2mesh’ pipeline), three coil types (circular, double-cone, and Figure-8), and 1000 coil placements (48,000 simulations). The real-time computation for any coil placement is within 4 milliseconds (ms), for 400 modes, and requires less than 4 GB of memory on a GPU. Our solver is capable of computing E-fields within 4 ms, making it a practical approach for integrating E-field information into the neuronavigation systems without imposing a significant overhead on frame generation. The software is available at https://github.com/NahianHasan/Real-Time-TMS.
Mapping multi-modal dynamic network activity during naturalistic music listening
Authors: Faber Sarah , Brown Tanya , Carpentier Sarah , McIntosh A.R.
Published: December 2024

The human brain is a complex, adaptive system capable of parsing complex stimuli and generating complex behaviour. Understanding how to model and interpret the dynamic relationship between brain, behaviour, and the environment will provide vital information on how the brain responds to real-world stimuli, develops and ages, and adapts to pathology. Modelling together numerous streams of dynamic data, however, presents sizable methodological challenges. In this paper, we present a novel workflow and sample interpretation of a data set incorporating brain, behavioural, and stimulus data from a music listening study. We use hidden Markov modelling (HMM) to extract state time series from continuous high-dimensional EEG and stimulus data, estimate time series variables consistent with HMM from continuous low-dimensional behavioural data, and model the multi-modal data together using partial least squares (PLS). We offer a sample interpretation of the results, including a discussion on the limitations of the currently available tools, and discuss future directions for dynamic multi-modal analysis focusing on naturalistic behaviours.
“I met my best friends yesterday”: Groups as a democratic practice in Brazilian schools
Authors: Mattos Amana Rocha , Carpes Barros Cassal Luan
Published: December 2024

In this paper, we analyse experiences of democratic practices in two research interventions within school contexts in Rio de Janeiro, Brazil. Both projects took place in public (Government-owned and managed) schools and were inspired by participatory and critical approaches, particularly Paulo Freire’s popular education and bell hooks’ feminist pedagogies. We analyse two case studies in which group interventions raise issues about democracy within schools and broader society, stressing the differences between the two contexts. The first case study discusses an educational programme for teachers and school staff on gender and sexual diversity, funded by a pro-diversity centre-left Federal government from 2007 to 2014. We analyse the group as a space to build multiple perspectives and democratic practices on gender and sexuality. Second, we analyse material from a project that conducted workshops with pupils (7 to 11 years old) to discuss interpersonal relations and the bonds they had with their schools during lockdowns (2021). Researchers developed participatory methods for remote learning and conducted online fieldwork with students—who had their parents’ and carers’ silent presence at home—analysing the construction of bonds with school, classmates and their autonomy. This project was conducted during a much more hostile moment than the previous one, during the COVID-19 pandemic lockdowns and in an ultraconservative political context in Brazil. While even during a social-democratic administration, we found limits in discussing gender and sexuality in schools (case study 1), the later authoritarian government and context severely worsened the situation (case study 2). Nevertheless, we were able to use critical approaches to promote and discuss democratic practices, especially considering gender, sexuality, race, and class inequalities. Through our practices as school psychologists and researchers, we make collective stands against authoritarianism.
Women’s Network Resource Acquisition in Informal Rural Entrepreneurship: A Developed View of Opportunity versus Necessity Dichotomy
Authors: Sharifi-Tehrani Mohammad , Seyfi Siamak , Vo-Thanh Tan , Zaman Mustafeed
Published: December 2024

This study explores the inherent interdependencies between microfinance social enterprises and two groups of women informal farm entrepreneurs and women informal tourism entrepreneurs in four impoverished rural regions in Iran. Using a qualitative constructivist grounded theory methodology, the findings suggest that women tourism entrepreneurs tend to engage in a greater coexistence of weak vertical and horizontal ties. In contrast, women farm entrepreneurs primarily develop strong horizontal ties. Consequently, members of the tourism group have greater opportunities to access a diverse range of resources, placing them in a more advantageous position along the opportunity–necessity entrepreneurship continuum. Guided by a network approach combined with strong structuration theory, this study develops a theoretical model that illustrates how these two groups of women entrepreneurs differently cope with gender constraints to grow their informal businesses. The findings highlight the need for tailored strategies and policies to empower various groups of subsistence women entrepreneurs.
Building Food Markets as a Method for Confronting the Rise of Authoritarian Populism: How the New Political Regime Has Forced Rural Movements to Create New Action Repertoires in Southern Brazil
Authors: Pizarro Muñoz Estevan Felipe , de Castro Camila Penna , Niederle Paulo André
Published: December 2024

This article examines how the political construction of food markets acts as a strategy for collective action with regards to three rural movements in Brazil: CONTAG, the MST, and Rede Ecovida. Each used food markets to confront the effects of a regime change that occurred with the rise of a populist authoritarian government. The research for this article was conducted between October 2017 and December 2020 through documentary analysis, observation, and interviews with social leaders. The results show how, since Jair Bolsonaro’s election as president, building new markets became vital to movements that sought to resist the influence of authoritarian populism as well as those that sought to dismantle public policies. A comparative analysis between the three movements also demonstrates how their diverse forms of organization and different political projects led to variations in how markets became privileged within larger political campaigns.

O artigo discute a construção política de mercados alimentares como estratégia de ação coletiva de três movimentos rurais brasileiros (CONTAG, MST e Rede Ecovida) em face da mudança de regime ocasionada pela ascensão de um governo populista autoritário. A pesquisa foi realizada entre outubro de 2017 e dezembro de 2020, por meio de análise documental, observação e entrevistas com lideranças sociais. Os resultados apontam que, a partir da chegada de Jair Bolsonaro à presidência, a construção de novos mercados tornou-se um componente essencial de resistência ao populismo autoritário e ao consequente desmantelamento das políticas públicas. A análise comparativa entre os três movimentos também demonstra que seus distintos formatos organizacionais e projetos políticos repercutem em diferenças com relação aos mercados privilegiados pela ação política.
The Association of Sleep Disturbance, Depression, and Kin Social Support With the College Adjustment of African American Students: A Moderated Mediation Model
Authors: Taylor Ronald D. , Bradford Jay , Joshi Crishnaa , Olaniyan Montunrayo , Gebre Azeb
Published: December 2024

This investigation examined whether the indirect association of sleep disturbance with college adjustment through depression was moderated by kin social support among African American college students. The study was grounded in the Integrative Model for the Study of Developmental Competencies in Minority Children (IM), which maintains that kin support promotes adaptive functioning of ethnic minority children and adults and moderates the effects of stressful experiences on adjustment. The hypotheses were assessed with online questionnaires administered to 152 African American college students (83% female, Mage = 21.7, SDage = 4.6). The findings revealed a significant indirect effect of sleep disturbance on college adjustment through depressive symptoms. Kin support moderated indirect effect, such that sleep disturbance was significantly associated with college adjustment through depressive symptoms, at low and moderate, but not high levels of kin support. The results suggest that it may be beneficial to incorporate sleep education among the student services administered on campuses. Developing mechanisms to link family and other sources of support with students’ campus life may be important for African American college students’ adjustment.
EP Thompson’s moral economy and legacy
Authors: Kirk Neville
Published: December 2024

This article offers a critical commentary upon historian EP Thompson’s pioneering research, carried out between the 1960s and 1980s, into the notion of moral economy. It addresses the main features of Thompson’s moral economy, his methodology and his profound, but also contested and ambivalent legacy to subsequent scholars. Set within the specific historical context of eighteenth-century England, Thompson’s moral economy revealed in new and original ways the often strained and conflict-ridden relations and actions between the working population and its rulers around the marketing of food and the price of bread. Thompson paid particular attention to food riots. They clearly illustrated the conflict, between, on the one hand, the traditional regulatory customs of some of the ruled and their supporters and the ‘free-market’ innovations of increasing numbers of their rulers. Thompson offered a historical-materialist reading of moral economy, situated in social contexts, relations and actions as well as in values and norms. Having addressed key empirical and methodological issues, the article proceeds to a critical examination of Thompson’s legacy. This covers the deep and widespread influence of Thompson’s moral economy, academically and geographically, its weaknesses as well as strengths and the ways in which he responded to reviews. In the last section, ‘Moral economy at the crossroads’, the article outlines and comments upon some of the key characteristics of the recent and ongoing single-, multi- and cross-disciplinary proliferation of studies of moral economy. It concludes by briefly indicating the ways in which future research into moral economy may fruitfully develop.
Symptom Burden and Quality of Life in Long-Term Survivors with Head and Neck Cancer
Authors: Gostian Magdalena , Allner Moritz , Rak Atina , Balk Matthias , Rupp Robin , Ostgathe Christoph , Mantsopoulos Konstantinos , Sievert Matti , Iro Heinrich , Hecht Markus , Gostian Antoniu-Oreste
Published: December 2024

Objectives: In this study, long-term survivors of head and neck cancer (HNC) were evaluated regarding their symptom burden and quality of life (QoL). Methods: This prospective study was performed during the regular follow-up consultations at one of Germany’s largest tertiary referral centers for HNC. The assessment included demographic, clinical, and oncological data, as well as the MIDOS(2) and the University of Washington Quality of Life Questionnaire (UW QoL) questionnaires. Patients were subdivided based on their disease stage, that is, early cancer stages (UICC I/II) and advanced cancer stages UICC (III/IV). Results: Between January 1, 2019 and December 31, 2019, 212 HNC patients with a mean follow-up of 46.36 ± 43.64 months were included (120 patients UICC stage I/II (22.5% female, mean age 61.93 ± 12.38 years) versus 92 patients UICC stage III/IV (25.0% female, mean age 63.73 ± 11.74 years)). For all patients evaluated (UICC I/II versus III/IV), the three most common symptoms were tiredness (47.5 vs 60.9%, P = .073, r = .123), anxiety (35.8 vs 32.6%, P = .624, phi = .034) and drowsiness (35.0 vs 44.6%, P = .157, phi = .097). Patients diagnosed with UICC III/IV stages reported loss of appetite significantly more frequently and with a high level of severity (15.0 vs 32.6%, P = .002, phi = .157; 0.23 ± 0.60 vs 0.47 ± 0.78, P = .003, r = .203). The overall symptom burden was low with a severity sum score (min 0-max 30) of 3.04 ± 3.29 versus 3.58 ± 3.38 ( P = .143, r = .100). All patients rated their QoL as good (65.67 ± 20.93 vs 59.56 ± 22.00, P = .043, r = .139). Conclusion: The overall symptom burden of long-term survivors of HNC is encouragingly low.

Trial registration: The study was registered in the German Registry for Clinical Studies (application No.: 00017122). Date of registration: 15.08.2019. https://drks.de/search/de/trial/DRKS00017122 .
Indigenous-municipal Intergovernmental Agreements: Policy Convergence by Region, Distance, or Cultural Similarity?
Authors: Alcantara Christopher , Brie Evelyne , Nelles Jen , Spicer Zachary
Published: December 2024

This paper examines policy convergence in Indigenous-local agreements in Canada using a dataset of 192 agreements collected between 2010 and 2014. It explores whether these agreements, which facilitate service sharing, contracting, and relationship formation, exhibit similarities across Indigenous communities, and whether these similarities are being driven by geographic location, proximity, or cultural similarity. Using word embeddings analysis, we find that culture is the strongest predictor of semantic similarity, with geographic location within the same province and proximity having much smaller effects.
Exploring Writer’s Block as Embodied Experience Across the Grades
Authors: Enriquez Grace , Vaughan Andrea
Published: December 2024

Background or Context:

The notion of writer’s block has been primarily conceived and explored as a breakdown in a cognitive writing process (Rose, 1984); yet, for many writers, confronting writer’s block often involves engaging the body through sensations, feelings, movement, and action. However, these considerations have not yet impacted our understanding of writer’s block in the field of literacy education. Given how attention to bodies and theories of embodiment have broadened considerations of literacies, we approach writing and writing processes (including not being able to write) as similarly embodied.

Purpose, Objective, Research Question, or Focus of Study:

Our purpose is to theorize writer’s block not only as a cognitive phenomenon, but also as an embodied one, and to offer that conceptualization for use in literacy theory, research, and practice. We ultimately argue that viewing writer’s block as an embodied phenomenon opens up possibilities for understanding writer’s block as not only restrictive, but also potentially generative, and can reframe understandings of “struggling” writers.

Research Design:

Drawing from our research across grades K–12, as well as our own experiences as writers, we present vignettes from elementary, middle school, high school, and adult contexts to illustrate how viewing writer’s block as embodied produces a more nuanced understanding of writers’ experiences. Moreover, because we engaged different research designs and methods for each study, we sought to “think with theory” (Jackson & Mazzei, 2012) across our work, rather than select a traditional qualitative analysis approach that might not have made visible the connections and nuances we sensed. These data and reflections are not intended to serve as complete, standalone case studies, but rather as illustrative examples to clarify our points.

Conclusions or Recommendations:

A more robust conception of writer’s block as something that is multidimensional (cognitive, social, cultural, affective, embodied, etc.) may allow for a fuller discussion of writing processes, as well as counter deficit assumptions of writers who appear to be “struggling,” including, in particular, Black, Indigenous, and students of color; disabled students; English learners; and other students who tend to be marginalized in official writing classroom contexts. Central to our framework are the following principles: (1) Bodies are an important medium through which writer’s block is recognized and expressed. (2) Writer’s block is socially co-constructed. (3) Writer’s block constitutes an intra-action with the human and nonhuman aspects of writing. (4) Despite appearing “stuck” or off-task, writers’ bodies are constantly charged with energy and possibility. With implications for practice and further research, this framework repositions writer’s block for students, teachers, and researchers from a deficit or remedial issue to an experience of writerly engagement, productivity, and possibility.
An Enquiry Into Modes of Non-Existence
Authors: Valkenburg Govert
Published: December 2024

After the many symmetries (subject-object, truth-falsity, etc.) that science and technology studies (STS) has explored, one symmetry seems unaddressed: the symmetry of explaining non-existence from the same kind of causes as existence. A social-constructivist perspective that articulates the work required to bring about existence cannot uncritically take for granted that the absence of such work simply explains non-existence. Rather, some non-existences are just as much “made,” and these non-existences “could have been otherwise.” In this article, I attempt to systematize this construction of non-existence under the notion of stifling. I first explore how the production of forms of non-existence has been thematized in scholarship in STS. I take non-things, non-knowledge, and non-people as the main classes to organize the arguments. I then propose a systematic approach to the ontological work performed through stifling and, notably, the consequences for what kind of futures this renders thinkable and unthinkable. Stifling then emerges as an important dynamic through which modal power is exercised and an indispensable element of ontological politics.
Neoliberalism’s Persistence and the Struggle for What Comes After
Authors: Firth Claudia
Published: December 2024

In this article I assess the contribution of works by Nancy Fraser and Wendy Brown on neoliberalism and the rise of right-wing populism. Both theorists report on monstrous and morbid symptoms that have emerged recently: the result of a crisis of hegemony for Fraser, and of contradictions in morality and moral conscience produced by neoliberalism, for Brown. Both also offer a feminist lens in relation to the politics of recognition and identity on the one hand, and wounded angry white maleness on the other. I discuss the differences in their particular contributions to post-Marxist debate and ways forward from the uneasy place in which we find ourselves, in which the moral authority of neoliberalism both wanes and continues to persist. Their work is of particular importance in understanding how subjects are enrolled into neoliberalism and, therefore, how alternative principles, practices and subjectivities, and new coalitions and alliances might be built.
Co-production in practice: A qualitative study of the development of advance care planning workshops for South Asian elders
Authors: Clabburn Oliver , Stone Tracey , Anwar Naheed , Saleem Taskin , Khan Salim , Hewat Verena , Grieve Usha , Dawson Lesel , Farr Michelle , Redwood Sabi , Selman Lucy E
Published: December 2024

Background:

Advance care planning can improve patient and family outcomes; however, minoritised ethnic communities experience access barriers. Co-production offers a way to design culturally appropriate information and support, but evidence is needed to understand its implementation in palliative care.

Aim:

To explore and describe how two charities used co-production to develop and deliver community-based advance care planning workshops for South Asian elders.

Design:

Workshops were co-produced by two charities. In parallel, a multi-component qualitative study was conducted comprising workshop observations, semi-structured interviews with charity staff and focus groups with workshop participants, facilitated by community co-researchers in English, Hindi, Urdu and Punjabi. Data were analysed using thematic analysis.

Setting/participants:

Four workshops were held in a London (UK) community setting (each with 5–30 participants); four interviews were conducted with charity staff members, and three focus groups with 16 workshop participants.

Results:

We describe three main themes: Co-production in action: organic origins and trusted foundations; Co-production processes embedded in equal partnership; and Impact of the workshops. Fundamental to co-production processes was the community-led approach of the local charity, the trust of the local South Asian community and the relationship between the charities, including transparent communication and mutual respect. The workshops were reported to be useful and enjoyable, engendering a sense of agency and connection and helped disseminate awareness and knowledge through the community, benefitting the wider system.

Conclusions:

Co-production can help widen access to advance care planning. Findings offer an in-depth example of co-production-in-action to inform intervention development and research.
Neuronal cytoplasmic inclusion bodies in the brain of Lagotto Romagnolo dogs: A qualitative and quantitative histologic evaluation
Authors: Peura Sini , Kiiskinen Elina , Jokinen Tarja S. , Virtala Anna-Maija K. , Syrjä Pernilla
Published: December 2024

Four neurologic diseases affect dogs of the Lagotto Romagnolo (LR) breed, namely benign familial juvenile epilepsy (BFJE), vacuolar storage disease, and 2 forms of cerebellar cortical degeneration. Intraneuronal inclusion bodies in cerebellar Purkinje cells were first described in the BFJE phenotype. Upon further characterization of these diseases, similar inclusions were also noted in the brain of LRs used as controls. This study investigated the clinical, histologic, and electron microscopic findings in 23 LRs to determine the nature of their neuronal inclusions and whether the presence, distribution, or number of inclusions is associated with neurologic signs. Electron microscopy of the inclusions revealed a cytoplasmic aggregate without a limiting membrane. The inclusions appeared proteinaceous on histochemical staining and positive on phosphotungstic-acid-hematoxylin (PTAH) stain for proteins rich in basic amino acids. Markers of commonly known proteinopathies of humans (ubiquitin, p62, LC3, α-synuclein, and β-amyloid) were not detected in the inclusions when assessed by immunohistochemistry. The overall presence of inclusion bodies was not significantly associated with the dog’s neurologic status. The results show an association between inclusions in the cerebral cortex and an absence of clinical neurologic disease in LRs. There was no significant difference in the quantitative inclusion body burden when compared in LRs with or without neurologic signs. Although PTAH-positive proteinaceous neuronal inclusions are a common finding in LRs regardless of neurologic signs, these inclusions may be a protective response when present in the cerebral cortex.
Effect of preventive treatment with atogepant on quality of life, daily functioning, and headache impact across the spectrum of migraine: Findings from three double-blind, randomized, phase 3 trials
Authors: Gottschalk Christopher , Gandhi Pranav , Pozo-Rosich Patricia , Christie Suzanne , Tassorelli Cristina , Stokes Jonathan , Liu Yingyi , Luo Lei , Nagy Krisztian , Trugman Joel M. , Lipton Richard B.
Published: December 2024

Background

We aimed to assess the effects of preventive migraine treatment with atogepant vs. placebo on patient-reported quality of life and functioning.

Methods

Analyses of patient-reported outcomes from three 12-week, randomized, placebo-controlled trials evaluating preventive migraine treatment with atogepant 60 mg once-daily: ADVANCE (low-frequency episodic migraine [LFEM], 4–8 monthly migraine days [MMDs] and high-frequency episodic migraine [HFEM], 8–14 MMDs), PROGRESS (chronic migraine, CM) and ELEVATE (episodic migraine in those previously failed by two to four classes of oral preventive treatments).

Results

Least squares mean differences (95% confidence interval (CI)) in change from baseline were greater ( p < 0.05) for atogepant vs. placebo for Migraine-Specific Quality of Life questionnaire Role Function–Restrictive domain scores at week 12 (ADVANCE: LFEM 12.0 (95% CI = 6.0–18.0), HFEM 9.9 (95% CI = 3.4–16.4); PROGRESS: 6.2 (95% CI = 2.5–9.8); ELEVATE: 17.7 (95% CI = 13.1–22.3)), for Headache Impact Test-6 total scores at week 12 (ADVANCE: LFEM −4.7 (95% CI = −6.7 to −2.7); HFEM −3.4 (95% CI = −5.5 to −1.2); PROGRESS: −2.8 (95% CI = −4.1 to −1.4); ELEVATE: −6.5 (95% CI = −8.3 to −4.7)) and for Activity Impairment in Migraine–Diary-Performance of Daily Activities scores across 12 weeks (ADVANCE: LFEM −2.3 (95% CI = −3.9 to −0.7), HFEM −4.5 (95% CI = −6.9 to −2.2); PROGRESS: −3.4 (95% CI = −5.3 to −1.5); ELEVATE: −4.7 (95% CI = −6.4 to −3.1)).

Conclusions

Preventive migraine treatment with atogepant 60 mg once-daily vs. placebo improved measures of migraine-related quality of life and functioning among participants with different headache frequencies and histories of previous treatment failure. Trial Registration: ClinicalTrials.gov: NCT03777059 (ADVANCE); NCT03855137 (PROGRESS); NCT04740827 (ELEVATE)
Disclosing Past Adult Sexual Assault to Romantic Partners: A Mixed-Methods Analysis
Authors: Person Abby I. , Frazier Patricia A. , Simpson Jeffry A.
Published: December 2024

The primary aim of the current mixed-method study was to examine factors that predict adult sexual assault disclosure in romantic relationships and understand how romantic partners respond if survivors choose to disclose their experiences to them. Sexual assault survivors ( N = 330; 93% cisgender women) completed online surveys assessing disclosure and various factors that might be associated with disclosure, and described how their partner responded to their disclosure or what prevented them from disclosing (qualitatively coded). Many victims did not disclose experiences of assault to their partners. Proportional odds logistic regression revealed that survivors who perceived their partners as more responsive were more likely to have disclosed, but partner trust was unrelated to disclosure. Attachment avoidance (but not anxiety) was negatively related to disclosure. Sexual and gender minority victims were more likely to have disclosed to their partners; race was unrelated to disclosure. The most common qualitative response was that partners reacted to disclosures with emotional support, although some responded negatively. Survivors most often chose not to tell their partners because the assault was too difficult to talk about or was not relevant to the relationship. Sexual assault stigma may play out in victims’ disclosure decisions and partners’ disclosure reactions.
Special Educators’ Knowledge of Foundational Reading Skills: A Review of the Literature
Authors: Trezek Beverly J. , Zepp Lauren
Published: December 2024

Teachers’ knowledge of foundational reading skills (e.g., phonemic awareness, phonics, fluency, vocabulary, comprehension) and the impact of this knowledge on the ability to provide effective reading instruction has been a topic of interest in teacher preparation for decades. Given the number of students with disabilities with significant instructional needs in reading, understanding the knowledge and skills of special educators and effective approaches for improving teachers’ knowledge is especially critical. Therefore, a systematic narrative review of the literature was conducted to identify studies that employed survey methods to examine special educators’ knowledge of foundational reading skills. The results of 18 studies published between 2001 and 2020 revealed that most investigations focused on assessing knowledge of the phonological aspects of reading. Furthermore, inconsistent performance and knowledge gaps were identified both within and across studies. Detailed summaries of studies are provided and recommendations for future research and practice explored.
Asking for Traces: A Vignette Study on Acceptability Norms and Personal Willingness to Donate Digital Trace Data
Authors: Silber Henning , Breuer Johannes , Felderer Barbara , Gerdon Frederic , Stammann Patrick , Daikeler Jessica , Keusch Florian , Weiß Bernd
Published: December 2024

Digital trace data are increasingly used in the social sciences. Given the risks associated with data access via application programming interfaces (APIs) as well as ethical discussions around the use of such data, data donations have been proposed as a methodologically reliable and ethically sound way of collecting digital trace data. While data donations have many advantages, study participants may be reluctant to share their data, for example, due to privacy concerns. To assess which factors in a data donation request are relevant for participants’ acceptance and decisions, we conducted a vignette experiment investigating the general acceptability and personal willingness to donate various data types (i.e., data from GPS, web browsing, LinkedIn/Xing, Facebook, and TikTok) for research purposes. The preregistered study was implemented in the probability-based German Internet Panel (GIP) and gathered responses from n = 3821 participants. Results show that people rate the general acceptability of data donation requests higher than their own willingness to donate data. Regarding the different data types, respondents indicated that they would be more willing to donate their LinkedIn/Xing, TikTok, and GPS data compared to web browsing and Facebook data. In contrast, information about whether the donated data would be shared with other researchers and data security did not affect the responses to the respective donation scenarios. Based on these results, we discuss implications for studies employing data donations.
Surgical planning in HTO – alternative approaches to the Fujisawa gold-standard
Authors: Komnik Igor , Funken Johannes , Zachow Stefan , Schmidt-Wiethoff Rüdiger , Ellermann Andree , Potthast Wolfgang
Published: December 2024

Background

Presurgical planning of the correction angle plays a decisive role in a high tibial osteotomy, affecting the loading situation in the knee affected by osteoarthritis. The planning approach by Fujisawa et al. aims to adjust the weight-bearing line to achieve an optimal knee joint load distribution. While this method is accessible, it may not fully consider the complexity of individual dynamic knee-loading profiles. This review aims to disclose existing alternative HTO planning methods that do not follow Fujisawa's standard.

Methods

PubMed, Web of Science and CENTRAL databases were screened, focusing on HTO research in combination with alternative planning approaches.

Results

Eight out of 828 studies were included, with seven simulation studies based on finite element analysis and multi-body dynamics. The planning approaches incorporated gradual degrees of realignment parameters (weight-bearing line shift, medial proximal tibial angle, hip-knee-ankle, knee joint line orientation), simulating their effect on knee kinematics, contact force/stress, Von Mises and shear stress. Two studies proposed implementing individual correction magnitudes derived from preoperatively predicted knee adduction moments.

Conclusion

Most planning methods depend on static alignment assessments, neglecting an adequate loading-depending profile. They are confined to their conceptual phases, making the associated planning methods unviable for current clinical use.