bluuebunny/crossref_metadata_2025 huggingface dataset:
Enriched environment may improve secondary brain injury after traumatic brain injury by regulating the TLR2/NF-κB signaling pathway
Authors: Wu Muyao , He Xiaoyi , Gong Yating , Wang Chaoyu , Huang Yaqian , Gao Fan , Dang Baoqi
Published: November 2024

Background

Traumatic brain injury (TBI) can cause damage to the blood-brain barrier, resulting in neuroinflammatory reactions and brain edema that seriously affect the recovery of neurological function. We hypothesize that an enriched environment (EE) regulates the TLR2/NF-κB signaling pathway and thereby modulates the integrity of the blood-brain barrier to achieve neuroprotective effects.

Objective

This study evaluated the expression of toll-like receptor (TLR)-2 after TBI in a rat model, with the aim of determining whether TLR2/NF-κB improves secondary brain injury by inhibiting the release of inflammatory factors and reducing brain edema.

Methods

We established a TBI model using Sprague-Dawley rats and implemented EE intervention or TLR2 siRNA to reduce TLR2. Western-blot analysis, real-time PCR, immunofluorescence staining, ELISA, TUNEL and FJC staining, wet–dry methods, rotarod testing, and neurological scoring were then applied for analysis.

Results

Our results revealed that TLR2 was activated after TBI in rats and that EE or silencing of TLR2 with TLR2 siRNA reduced the level of inflammation, significantly alleviating brain edema, neuronal apoptosis, and degeneration. TBI exacerbated brain edema and nerve damage caused by TLR2/NF-κB signaling, and EE appeared to regulate neuroinflammation and brain edema by reducing TLR2.

Conclusions

Inhibition of TLR2 with EE might constitute a successful approach in the management of TBI.
An organisational autoethnography of learning to manage academic workplace bullying through micro-resistance and activism
Authors: Sambrook Sally
Published: November 2024

This article is about voice – I use my voice to speak out, and hopefully be heard. I am talking about workplace bullying and humiliation in higher education, and particularly in a business school, that caused abject disengagement. I articulate my pitiful, painful story through autoethnography. In doing so, I contribute to both the writing differently movement and to the growing critique of higher education. In attempting to deal with workplace bullying, I draw on theories of silence/exit/voice, complaint and disappointment as well as micro-resistance and subtle activism. My purpose is to give voice to bullying and humiliation so others (especially managers) might understand what it feels like, to learn how to deal with it individually (especially those being bullied and humiliated) and to learn how collectively we might act to address it, through micro-resistance and subtle activism.
Journalists as individual users of artificial intelligence: Examining journalists’ “value-motivated use” of ChatGPT and other AI tools within and without the newsroom
Authors: Wu Shangyuan
Published: November 2024

ChatGPT and other AI applications have made the widespread use of artificial intelligence possible with their conversational interfaces and open accessibility – this “mainstreaming” of AI use has become concerning for news organizations as they grapple with the creation of appropriate AI-related guidelines and tools for their newsrooms. Even while such discussions are ongoing, the cultural shift among journalists has already begun. This paper highlights the role of journalists not simply as agents working within the confines of news organizations, but as actors with individual agency to enact change. Their use of AI has already gained significant momentum, with or without newsroom oversight and direction. This paper, supported by field theory, uses in-depth interviews with journalists and editors to uncover how journalists are themselves using AI in their day-to-day work, and how they ensure their values of “good journalism” are not compromised. Results show that journalists are already personally using AI in numerous tasks across all the stages of news production, namely in news gathering, news writing and presentation, news editing, and news promotion, and have three strategies to maintain their practice of “good journalism”. These results prompt the paper’s proposition of a new “value-motivated use” perspective to summarize journalistic adoption of AI – that it is the journalistic values that motivate their increased use of AI, as well as the values that motivate their limitations of this use; journalists will use the technology only to the extent that it aligns with the values of their profession.
Collaboration in the humanities: Teaching and learning together
Authors: Dush Lisa
Published: November 2024

Collaboration is not a core practice in humanities teaching and learning, despite convincing arguments that it should be. To encourage collaboration in classrooms and with communities, DePaul University has developed its Experiential Humanities Collaborative. The Collaborative connects faculty, community partners, and students to co-design and implement new community-engaged, project-based humanities courses. This article outlines several rationales for collaboration in the humanities, situates the approaches of the Experiential Humanities Collaborative among those of similar initiatives, and shares outcomes from the project’s early years. While teaching and learning the humanities will always involve independent reading, reflection, and writing, the Collaborative demonstrates the value, as well as the challenges, of adding collaboration to these core practices.
Late-Onset Temporal Lobe Epilepsy—Differentiating the Gray Matter from the Matter of Gray
Authors: Marawar Rohit
Published: November 2024

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Defying the Leviathan: Community-based and intersectional approaches to decolonial leadership in Guatemala
Authors: Rodríguez Álvarez Gloriana
Published: November 2024

This paper examines decolonial leadership in Guatemala, focusing on how Indigenous and marginalised communities resist colonial and authoritarian structures through community-based and intersectional approaches. Resistance to systemic injustices is not merely a reaction but an intrinsic part of Guatemala’s historical and social fabric. Based on interviews with Indigenous leaders, feminists, LGBTQ advocates, and legal experts from 2019 to 2023, the study contests Western-centric leadership paradigms. Findings reveal that resistance movements adhere to a collective leadership rooted in community and intersectionality, integrating Indigenous knowledge systems and communitarian feminism. The community-based approach critiques individualism, hierarchical structures, and anthropocentrism. Thus, decolonial leadership underscores the interconnectedness of humanity and nature, reframing leadership as an inclusive, contextually grounded practice. Moreover, the intersectional approach highlights the role of diverse identities, specifically examining race/ethnicity, gender, and class dimensions. This study seeks to present a counter-narrative that values local knowledge and cultural specificity, providing a nuanced perspective on leadership as a means to dismantle colonial hierarchies and address systemic injustices. As such, the paper seeks to contribute to a leadership discourse that reflects a plurality of voices, perspectives, and contexts, thereby broadening the field with a more representative understanding of leadership practices.
Diversity in the editorial boards of medical journals: a perspective from the Middle East
Authors: Dakhil Zainab Atiyah , Marsool Mohammed Dheyaa Marsool , Qasim Mohammed Saad , Al-Jorani May Saad
Published: November 2024

Despite the significant increase in women in academic medicine over the last 50 years, women are still under-represented in leadership positions in academia. However, there is a lack of data on the diversity of editorial boards in Middle Eastern medical journals. So, we aim to portray the diversity of editorial boards of Iraqi medical journals by conducting a cross-sectional analysis of the editorial boards’ members of all Iraqi medical journals. Gender, affiliation and specialty were extracted from the journals’ websites and/or from the professional profiles of the editorial board members. Twenty-five journals and 446 editorial board members were analysed. More than half of editorial board members specialized in basic science, while 39.76% specialized in clinical specialties. Approximately, 20.18% of editorial board members (regardless their role) were women. Four percent of editor-in-chief were women. There were significant differences in editorial role according to gender ( p < 0.0001), yet residency ( p = 0.688) and specialty ( p = 0.190) did not differ according to their gender. Most editorial board members were affiliated with Baghdad. So, we can conclude that there is a significant under-representation of women across all roles on the editorial board of medical journals especially in the leading positions. All stakeholders, publishers, authors and academics should commit to ensure the diversity of editorial boards.
Clinical and radiological implications of subpotent generic fingolimod in multiple sclerosis: a case series
Authors: Okuda Darin T. , Tardo Lauren M. , Wright Crystal M. , Munoz Shanan B. , Punnen Tom G. , Patel Mahi A. , Moog Tatum M. , Burgess Katy W.
Published: November 2024

An expansion in the availability of generic specialty disease modifying therapies (DMTs) for treatment of multiple sclerosis (MS) has increased recently. Generic specialty medications aim to provide greater access to molecules that alter the disease trajectory at lower costs. The US Food and Drug Administration requires generic products to contain between 90% and 110% of the stated active ingredient and an 80%–125% bioequivalence range. We present the clinical experiences and absolute lymphocyte counts (ALC) trends of six people with MS originally treated with Gilenya® (fingolimod) 0.5 mg who were required to transition to generic fingolimod 0.5 mg by third-party administrators, and the medication content from recovered products. Six individuals with acute clinical exacerbations or disease advancement on MRI were identified during routine scheduled visits from a tertiary care center and consecutively included from January 2024 to August 2024. ALC trends were constructed for each individual during Gilenya® and generic fingolimod treatment. These individuals experienced signs of disease advancement while on generic fingolimod 0.5 mg at approximately 1 year of treatment and elevations in ALC, a biological metric related to the mechanism of action of sphingsine-1-phosphate receptor modulation, were observed following the transition. High purity fingolimod for standardization tests, Gilenya® 0.5 mg, and five recovered generic fingolimod 0.5 mg products were independently tested in an accredited laboratory. Gilenya® 0.5 mg capsules had an average fingolimod content of 97.7% (standard deviation (SD) = 2.59%). Three recovered generic fingolimod 0.5 mg products used during relapses had an average content of 91.2% (3.25%), 81.6% (6.24%), and 72.5% (2.05%). Two generic fingolimod 0.5 mg products not associated with relapse activity revealed averages of 97.4% (1.82%) and 103.3% (3.77%). Subpotent generic specialty DMTs may not only result in greater risk for disease activity but may also expose individuals to the potential for disease rebound, depending on the mechanism of action.
Residual temporal convolution network with novel activation function for financial prediction with feature selection procedures
Authors: Ahmad Ahmad YA Bani
Published: November 2024

Finance provides a major contribution to countries economic growth. A deep understanding of the financial market helps to offer better financial returns in the future. The financial market generates more complications for predicting the complicated system dynamics. Different machine learning techniques are implemented to execute the financial market prediction and they didn’t provide better outcomes in financial returns. Predicting the stocks in the yearly phases brings huge profits to the stock market traders and helps to make better financial decisions. Different deep learning and machine learning techniques help to predict the accuracy of the stock market. The deep learning techniques effectively handled the enormous unsupervised and unstructured data. In order to achieve better results, the intelligent deep learning model is proposed for forecasting the financial crisis. Initially, the raw data are fetched from the benchmark datasets. Subsequently, the multi-objective-based feature selection process takes place, where the features are optimally selected by using the Updated Random Variable-based Coati Optimization Algorithm (URV-COA). Due to this selection, various constraints like correlation, relief score, and data variance are considered for formulation. Finally, the resultant features are subjected to the Residual Temporal Convolutional Network with a Novel Activation function (RTCN-NAF) for predicting the financial cost. Therefore, the experimentation for the proposed model is assessed by using the divergent metrics and compared with other traditional methodologies. On the contrary, the suggested work achieves better results that can prove the effectiveness of the prediction system.
Postcolonial repetitions: Distant time in the imaginary of India’s smart cities
Authors: Ghertner D. Asher
Published: November 2024

This commentary uses contemporary Hindi cinema to suggest that the strange cosmologies of building files in India and the repetitions and re-narrations of past events that structure the letters and petitions that compose those files are steeped in a wider (post)colonial literary–cinematic imaginary. The technics of time richly explored in Ayona Datta's essay are hence shaped by and shape cultural forms, such as films and state development narratives. The promises of the future smart city cannot be understood outside of the repetitions and deferrals of the past city or the affectively saturated notions of temporality prominent in such cultural forms. Perhaps the fantasy of planning the smart city is as speculative and surreal, as nostalgic of colonial pasts, and as saturated in phantasmic affects, as Bollywood heroism.
Long-term sildenafil therapy for pulmonary veno-occlusive disease in association with melphalan therapy for multiple myeloma: A case report
Authors: Hesse Christian , Kovacs Gabor , Scheidl Stefan , Olschewski Horst
Published: November 2024

Pulmonary veno-occlusive disease has a significantly worse prognosis than idiopathic pulmonary arterial hypertension. According to a case series from France, the median survival time from diagnosis to death or lung transplantation was only 1 year, and in a more recent analysis, pulmonary arterial hypertension therapy had no significant effect on survival. There are case reports and case series describing both beneficial and adverse effects of pulmonary arterial hypertension-related medications. The most life-threatening complication of such a therapy is pulmonary oedema. In the long term, lung transplantation remains the best treatment option for suitable patients. However, elderly patients with concomitant or precipitating malignant disease are not considered transplant candidates. We describe a 59-year-old pulmonary veno-occlusive disease patient with multiple myeloma in World Health Organisation functional class IV who was successfully treated with sildenafil for almost 5 years.
A rare case of cryptococcal meningitis with infarction of the splenium of the corpus callosum in an immunocompetent patient: A case report
Authors: Hojat Ansari Sahar , Rahimzadeh Somayeh
Published: November 2024

Meningitis is a severe infection of the central nervous system. Cryptococcus neoformans is an uncommon fungal agent that can cause meningitis and often manifests unusual symptoms. While this infection is more prevalent in immunocompromised patients, it can also affect immunocompetent patients. A 33-year-old housewife living in the village visited our hospital emergency department complaining of a severe headache and mild fever for 7 days. We diagnosed an unusual occurrence of cryptococcal meningitis with infarction of the splenium of the corpus callosum in a patient who appeared to have a healthy immune system. This disease should be considered in immunocompetent individuals with persistent headache or other neurological findings, even in the absence of overt risk factors.
Parental expectations of school counsellors and their role in supporting student mental health and wellbeing: A qualitative study
Authors: Collins Glenn , Kovac Katya , Rigney Gabrielle , Benveniste Tessa , Gerace Adam , Dittman Cassandra K. , Vincent Grace E
Published: November 2024

By working in partnership with parents, school counsellors can assist in the early identification of mental health and wellbeing issues and facilitate timely access to professional support. However, very little is known about parents’ understanding of the role of school counsellors and the barriers and enablers influencing the relationship between parents and school counsellors. Therefore, this qualitative study employed one-on-one interviews of 10 parents and employed a reflexive thematic analysis approach. Results revealed that parents expect school counsellors to provide a safe and supportive environment for students. Parents believe the school counsellor should be offering curriculum and behaviour support to teachers, individual and group work to students, and career counselling. In terms of the barriers and enablers influencing collaboration between school counsellors and parents, participants overwhelmingly felt that the role was hidden away and ill-defined. Advertising services more and getting the counsellor out into the school community at times suitable to working parents were seen as important considerations. Parents value the role of school counsellors. Future research on parental attitudes towards school counsellors could gain insights by diversifying participant profiles, including various genders, socio-economic backgrounds and occupations, to capture a wider range of perspectives.
Can Social Media Engagement Predict Election Results? Bandwagon Effects of Tweets About US Senate Candidates
Authors: Wang Jinping , Sundar S. Shyam , Ram Nilàm
Published: November 2024

The social media platform X (formerly Twitter) has grown to become an important venue for political discourse, with candidates using it integrally in their election campaigns. However, it is not clear if activity on Twitter can be used to forecast elections, given conflicting findings in the literature. By analyzing 830,796 tweets mentioning key hashtags related to nine US senate races in 2014, 2016, and 2018, we demonstrate that cascades in volume and sentiment of tweets between September 1 and Election Day can predict election outcomes. We developed a non-linear growth modeling tool to identify the point in time at which bandwagon support for competing candidates begins to diverge. We also discovered that bot-driven tweets play a negligible role. We discuss theoretical and practical implications for both computational research and media effects, showing the value of combining big-data analysis and longitudinal non-linear dynamics to study the relationship between social media activity and real-world outcomes.
Early Outcomes for Management of Atrioventricular Septal Defect—Tetralogy of Fallot in the Last Decade: A Congenital Heart Surgeons’ Society Study
Authors: Callahan Connor P. , Argo Madison B. , McCrindle Brian W. , Barron David J. , Jegatheeswaran Anusha , Honjo Osami , Polimenakos Anastasios C. , Turek Joseph W. , Dabal Robert J. , Kirklin James K. , DeCampli William M. , Eghtesady Pirooz , Overman David M. ,   the Congenital Heart Surgeons’ Society AVSD-TOF Working Group
Published: November 2024

Background

We sought to determine the management and early outcomes of complete atrioventricular septal defect—tetralogy of Fallot (AVSD-TOF) for a contemporary multicenter cohort.

Methods

Of 739 participants in the Congenital Heart Surgeons' Society AVSD cohort (January 2012-May 2021), 40 had AVSD-TOF. We first compared survival differences for patients with AVSD-TOF versus those with isolated AVSD using propensity matching. Secondly, for patients with AVSD-TOF, we compared staged (n = 16) versus primary (n = 24) repair by assessing the following: patient characteristics, progression of atrioventricular valve (AVV) regurgitation, and time-related reoperation and survival.

Results

Five-year survival was similar between matched AVSD-TOF and isolated AVSD groups (80% vs 81%, P = .9). Compared with primary repair patients, staged patients had smaller pulmonary valve annulus Z-score measured at first presentation (−2.2 vs −2.9, P = .006). All staged patients (12 Blalock-Thomas-Taussig shunts, 3 right-ventricular-outflow-tract stents, 1 ductal stent) survived to complete repair. Freedom from AVSD-related reoperation five years post-AVSD-TOF repair was 57% after staged versus 90% after primary repair ( P < .05) and left AVV reoperations were the most frequent reintervention. Survival five years after AVSD-TOF repair was 80% (63% after staged vs 90% after primary repair; P = .08).

Conclusions

Patients undergoing AVSD-TOF repair have similar survival compared with matched isolated AVSD patients. Although approximately half of AVSD-TOF patients had initial palliation and all survived to complete repair, staged repair patients had lower survival and a higher reintervention rate compared with primary repair patients. The decision to pursue staged versus primary repair for future babies with AVSD-TOF remains challenging and should be chosen based on individual circumstances.
The Relationship Between Social Sustainability Practices and Performance Outcomes in Supply Chain Management: The Case of Vietnam
Authors: Duong Ngoc Hong , Bui Thanh Trang , Ha Quang-An
Published: November 2024

Nowadays, both academic scholars and decision makers are raising much attentions to underscore the meanings of social sustainability practices to the success of firms, particularly in the context of emerging countries. Under the stakeholder resource-based view (SRBV) theory, the current research model was adopted to identify determinants of social sustainability practices and its linkages with performance outcomes of the supply chain. There were 204 valid samples collected from respondents who operate the supply chains in the Vietnamese medium and large enterprises. Empirical results indicated that social sustainability practices positively impact on the performance outcomes of the supply chain management. Critically, this study is among the very first-ever papers that significantly evidenced the mediating roles of customer performance and supplier performance in the relationship between a firm’s social sustainability practices and supply chain performance. The multidimensional concept of social sustainability has been extendedly incorporated in the context of Vietnamese companies, it provides managers and policy-makers useful insights for implementing social sustainability in the corporate sustainable development strategies.
U.S. and Canadian Higher Education Protests and University and Police Responses, 2012 to 2018
Authors: Berrey Ellen , Hanna Alex , Kim Nathan , Bass Kristen
Published: November 2024

The authors describe protest patterns at U.S. and Canadian universities in the 2010s. The research draws on a new dataset, the Higher Ed Protest Event Dataset, which combines machine learning and sociological hand coding of 16,069 campus newspaper articles. The sample consists of 5,553 higher ed protests involving 584 universities and colleges between 2012 and 2018. The dataset also includes university and police responses to a subset of protests. The authors find that protest frequency is patterned by the academic calendar. The top issue in both U.S. and Canadian higher education protests was university administration and governance. The comparative analysis reveals distinctive patterns in other issues raised and protest intensity. In the United States, the periods of greatest protest activity were waves of mass mobilization across the country on often racialized issues with a national dimension: racist police violence, racially hostile campus climates, and Donald Trump’s presidency. In Canada, protest activity was most intense during provincial or local campaigns led by formal student organizations and unions on issues of economic security: public tuition, austerity, and labor conditions. Across both countries, university administrations and police usually avoided extensive intervention during protests. The findings contribute to social movements research through methodological innovations and new empirical insights on movements in higher education.
The Role of Information Visualisation and Anecdotal Evidence in Medical Students’ Clinical Reasoning Process: A Cross-Sectional Survey Study
Authors: Janssen Anna , Goldwater Micah B. , Hilton Courtney B. , Bonner Carissa , Shaw Tim
Published: November 2024

BACKGROUND

Medical students are often taught clinical reasoning implicitly, rather than through a formal curriculum. Like qualified health professionals, they engage in a wide range of information seeking and other practices as part of the clinical reasoning process. This increasingly includes seeking out information online and being informed by anecdotal information from social media or peer groups. The aim of this research was to investigate how anecdotes and icon arrays influenced the clinical reasoning process of medical students deciding to prescribe a hypothetical new drug.

METHODS

A cross-sectional survey design was used. The survey required participants to respond to six hypothetical clinical scenarios in which they were asked to prescribe a hypothetical drug “polypill” for a specific patient. The order of delivery of the six scenarios was randomised for each participant. In response to each scenario, participants indicated how effective they perceived each drug to be. The study received ethics approval from the University of Sydney Human Research Ethics Committee: Protocol No: 2019/001. All participants provided written informed consent before agreeing to participate in the study.

RESULTS

A total of 56 medical students fully completed the survey. Statistical analysis of the responses indicated that the icon array may be effective for highlighting how the polypill reduces CVD risk, reducing the impact of anecdotes on efficacy judgments. Without the icon array, both the positive and negative anecdotes made participants less willing to prescribe the polypill.

CONCLUSIONS

Medical student clinical reasoning processes appear to be influenced by anecdotal information and data visualisations. The extent of this influence is unclear, but there may be a need to actively educate students about the influence of these factors on their decision-making as they graduate into a world where they will be increasingly interacting with anecdotal information on social media and visualisations of electronic data.
Access to Debt Finance in Sub-Saharan Africa: Redefining the Problem from Risk Perspective and Way Forward
Authors: Ogunmokun Olapeju Comfort , Mafimisebi Oluwasoye P. , Obembe Demola
Published: November 2024

This article presents critical points of view relating to small and medium-sized enterprises (SMEs) access to debt finance in Sub-Saharan Africa (SSA). The prevailing view suggests that lack of credit information is a fundamental factor that contributes to the constraints faced by SMEs. We challenge this prevailing dominant view and argue that SMEs are constraints in accessing debt finance due to banks’ risk assessment strategies. At the same time, it suggests that banks modelling credit risk assessment for SMEs in SSA became extremely crucial for determining access to debt finance. This impacts on access to debt finance contrary to the popular claim that the opaque nature of SMEs is the major constraint limiting access to debt finance. In such a challenging context, SMEs are expected to either provide more information to banks to reduce the problem of information asymmetry as well as provide collateral and guarantees in the absence of reliable information to safeguard against the risk of default or maintain a long-term relationship with banks which is expected to result in an increase in debt financing. The authors emphasise the need to redefine the problem of access to debt finance so that financing obstacles for SMEs can be strengthened. The implications and alternative strategies for SMEs’ access to debt finance are discussed.
How Statistical Challenges and Misreadings of the Literature Combine to Produce Unreplicable Science: An Example From Psychology
Authors: Gelman Andrew , Brown Nicholas J. L.
Published: November 2024

Given the well-known problems of replicability, how is it that researchers at respected institutions continue to publish and publicize studies that are fatally flawed in the sense of not providing evidence to support their strong claims? We argue that two general problems are (a) difficulties of analyzing data with multilevel structure and (b) misinterpretation of the literature. We demonstrate with the example of a recently published claim that altering patients’ subjective perception of time can have a notable effect on physical healing. We discuss ways of avoiding or at least reducing such problems, including comparing final results with simpler analyses, moving away from shot-in-the-dark phenomenological studies, and more carefully examining previous published claims. Making incorrect choices in multilevel modeling is just one way that things can go wrong, but this example also provides a window into more general problems with complicated designs, cutting-edge statistical methods, and the connections between substantive theory, experimental design, data collection, and replication.
Progressive damage for 3D printed composites with variable fiber volume content and ply location
Authors: Meng Zhe , Yali Yang , Lu Lei , Chen Hao , Xu Sha , Li Yongfang , Zhang Ruoping , Zhou Tianjun
Published: November 2024

At present, 3D printed continuous carbon fiber reinforced composites (CCFRCs) are widely used in aviation and automotive fields. Most of the existing research on 3D printed CCFRCs focuses on fiber volume content and rarely explores the specific fiber ply location. However, the latter is one of the most important factors affecting the strength and stiffness properties of materials. In this paper, the constitutive model and progressive damage model of 3D printed CCFRCs are established, concentrating on the fundamental aspects of fiber volume content and fiber ply location. The mechanical properties of 3D printed CCFRCs with different fiber volume content and fiber ply location were studied by tensile tests. The mapping relationship between mechanical properties and fiber volume content and fiber ply location was obtained based on experimental data. In addition, the failure morphology and microstructure of the sample at the fracture section were analyzed, and the failure process under different fiber angles was studied to reveal the failure mechanism. The progressive damage model was used to predict and analyze the performance of 3D printed CCFRCs with different fiber volume content and fiber ply location. The results show that the feasibility and effectiveness of the present model are verified through the comparison between experiment and simulation.
CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AML
Authors: Silva Harrison J. , Martin Grace , Birocchi Filippo , Wehrli Marc , Kann Michael C. , Supper Valentina , Parker Aiyana , Graham Charlotte , Bratt Alexandra , Bouffard Amanda , Donner Hannah , Escobar Giulia , Takei Hana , Armstrong Alexander , Goncalves Sadie , Berger Trisha R. , Choi Bryan D. , Maus Marcela V. , Leick Mark B.
Published: November 2024

CD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based chimeric antigen receptor (CAR). However, here, we identify in vivo CD70 antigen escape as a limitation of single-antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity. We hypothesized that modifying our CD70 CAR platform to secrete a bispecific T-cell engaging antibody molecule (TEAM) targeting CD33 (7033) would create a therapeutic window whereby AML heterogeneity could be addressed without increasing tissue toxicity. We found that CD33 TEAMs mediated specific cytotoxicity across AML cell lines, including CD33 or CD70 single-antigen knockout tumors. 7033 CAR T cells eradicated tumor in an in vivo mixed tumor model of CD70 antigen escape and outperformed the previously optimized CD70 CAR in a patient-derived xenograft. In vivo gene expression profiling of CAR T cells revealed enhanced 7033 CAR T-cell pathway scoring for persistence, activation, and T-cell receptor signaling. Additionally, CD33 TEAMs successfully redirected T cells isolated from patients with AML to activate, secrete cytokines, and kill tumor targets despite exposure to substantial prior cytotoxic therapies. In summary, our findings demonstrate the feasibility of our 7033 CAR to overcome AML heterogeneity and leverage the bystander T cells of patients; this approach warrants further study in patients with this dire clinical need.
Development of hyperdiploidy starts at an early age and takes a decade to complete
Authors: Samur Mehmet K. , Aktas Samur Anil , Shah Parth , Park Joseph S. , Fulciniti Mariateresa , Shammas Masood , Corre Jill , Anderson Kenneth C. , Parmigiani Giovanni , Avet-Loiseau Hervé , Munshi Nikhil C.
Published: November 2024

Nearly half of patients with multiple myeloma (MM) have hyperdiploidy (HMM) at diagnosis. Although HMM occurs early, the mutational processes before and after hyperdiploidy are still unclear. Here, we used 72 whole-genome sequencing samples from patients with HMM and identified pre- and post-HMM mutations to define the chronology of the development of hyperdiploidy. An MM cell accumulated a median of 0.56 mutations per megabase before HMM, and for every clonal pre-HMM mutation, 1.21 mutations per megabase accumulated after HMM. This analysis using mutations before and after hyperdiploidy shows that hyperdiploidy happens after somatic hypermutation. Prehyperdiploidy mutations are activation-induced cytidine deaminase and age/clock-like signature driven, whereas posthyperdiploidy mutations are from DNA damage and APOBEC. Interestingly, the first hyperdiploidy event occurred within the first 3 decades of life and took a decade to complete. Copy number changes affecting chromosomes 15 and 19 occurred first. Finally, mutations before initiating event affected chromosomes at different rates, whereas post–initiating event mutational processes affect each chromosome equally.
Introduction to a review series on von Willebrand factor, factor VIII, and factor IX
Authors: Ortel Thomas L.
Published: November 2024

Edited and introduced by Associate Editor Thomas Ortel, this review series features 3 reviews of von Willebrand factor, factor VIII, and factor IX. These 3 proteins are functionally intertwined, and insights into their structure, molecular interactions, and modifications have led to important advancements in therapies for hemophilia A and B and for treatment for thrombotic thrombocytopenic purpura.
Chronic inflammation deters natural killer cell fitness and cytotoxicity in myeloid leukemia
Authors: Kuznetsova Valeriya , Krishnan Vaidehi , Costa Amanda , Ren Xi , Ricketts Tiffany D. , Patel Sweta B. , Connelly Ashley N. , Goel Paran , Knapp Joshua P. , Franceski Alana M. , Luca Francesca , Lobo de Figueiredo-Pontes Lorena , Bhatia Ravi , Prabhakar Shyam , Ong S. Tiong , Welner Robert S.
Published: November 2024

Natural killer (NK) cells play an integral role in immunosurveillance against myeloid malignancies, with their mature phenotype and abundance linked to prolonged treatment-free remission in chronic myeloid leukemia (CML). However, NK cell function is suppressed during the disease, and the orchestrators of this impairment are not fully understood. Using a chimeric BCR::ABL1+ CML mouse model, we characterized the impact of the leukemic microenvironment on NK cell function. We showed that NK cells have reduced counts, immature phenotype, poor cytotoxicity, and altered expression of activating and inhibitory receptors in CML mice, which revert to a steady state upon BCR::ABL1 inhibition. Single-cell RNA sequencing revealed an inflammatory cytokine response in CML-exposed NK cells, highlighted by the tumor necrosis factor α (TNFα)-induced gene signature, upregulation of TNFα receptor 2, and enrichment of suppressor of cytokine signaling family genes such as Cish, the critical NK cell checkpoint. Ex vivo exposure of healthy NK cells to leukemic soluble factors compromised target-specific NK cell degranulation, which was partially rescued by targeting Cish or TNFα. In alignment with these findings, NK cells from healthy donors displayed suppressed cytotoxicity when exposed to plasma from untreated patients with CML, with a partial restoration upon Cish or TNFα inhibition. Furthermore, NK cells from newly diagnosed patients with CML predestined for blast crisis showed an enrichment of the TNFα-induced proinflammatory gene signature identified in CML mice. These results suggest that targeting inflammatory signaling could enhance NK cell-based immunotherapies for CML.
“Infectious uveitis: a comprehensive systematic review of emerging trends and molecular pathogenesis using network analysis”
Authors: Asghar Muhammad Arif , Tang Shixin , Wong Li Ping , Yang Peizeng , Zhao Qinjian
Published: November 2024

Background

Infectious uveitis is a significant cause of visual impairment worldwide, caused by diverse pathogens such as viruses, bacteria, fungi, and parasites. Understanding its prevalence, etiology, pathogenesis, molecular mechanism, and clinical manifestations is essential for effective diagnosis and management.

Methods

A systematic literature search was conducted using PubMed, Google Scholar, Web of Science, Scopus, and Embase, focusing on studies published in the last fifteen years from 2009 to 2023. Keywords included “uveitis,” “infectious uveitis,” “viral uveitis,” and others. Rigorous inclusion and exclusion criteria were applied, and data were synthesized thematically. Gene symbols related to infectious uveitis were analyzed using protein-protein interaction (PPI) networks and pathway analyses to uncover molecular mechanisms associated with infectious uveitis.

Results

The search from different databases yielded 97 eligible studies. The review identified a significant rise in publications on infectious uveitis, particularly viral uveitis, over the past fifteen years. Infectious uveitis prevalence varies geographically, with high rates in developing regions due to systemic infections and limited diagnostic resources. Etiologies include viruses (39%), bacteria (17%), and other pathogens, substantially impacting adults aged 20–50 years. Pathogenesis involves complex interactions between infectious agents and the ocular immune response, with key roles for cytokines and chemokines. The PPI network highlighted IFNG, IL6, TNF, and CD4 as central nodes. Enriched pathways included cytokine-cytokine receptor interaction and JAK-STAT signaling. Clinical manifestations range from anterior to posterior uveitis, with systemic symptoms often accompanying ocular signs. Diagnostic strategies encompass clinical evaluation, laboratory tests, and imaging, while management involves targeted antimicrobial therapy and anti-inflammatory agents.

Conclusion

This review underscores the complexity of infectious uveitis, driven by diverse pathogens and influenced by various geographical and systemic factors. Molecular insights from PPI networks and pathway analyses provide a deeper understanding of its pathogenesis. Effective management requires comprehensive diagnostic approaches and targeted therapeutic strategies.
Subgroup differences in public attitudes, preferences and self-reported behaviour related to deceased organ donation before and after the introduction of the ‘soft’ opt-out consent system in England: mixed-methods study
Authors: Boadu Paul , McLaughlin Leah , Noyes Jane , O’Neill Stephen , Al-Haboubi Mustafa , Williams Lorraine , Bostock Jennifer , Mays Nicholas
Published: November 2024

Background

In the UK, over 7,000 people are on the waiting list for an organ transplant and there are inequalities in need, access and waiting time for organs, with notable differences between minority ethnic groups. In May 2020, England changed the law and introduced a ‘soft’ opt-out system of consent to organ donation with a view to increase consent rates. We aimed to learn more about the impact of the law change on attitudes and views likely to be relevant to consent to deceased organ donation between different population subgroups.

Methods

Mixed-methods design involving latent class analysis of data from twelve repeated cross-sectional surveys undertaken from 2015 to 2021 (n = 19,011); analysis of the law change survey dataset collected quarterly from 2018 to 2022 (n = 45,439); and interviews with purposively selected members of the public (n = 30) with a focus on minority perspectives.

Results

Support for the principle of deceased organ donation remained high and stable in the general population (80%) but was 20% lower among ethnic minorities. From 2018 to 2022, an average of 58% of the general population was aware of the law change; this was lower among minority ethnic groups (31%). We identified four population subgroups (supportive donors (24% of the population); unengaged donors (22%); uncommitted donors (46%); and unsupportive donors (9%)). Interview themes included the challenges of discussing organ donation decisions, balancing autonomy with respecting family relationships, targeted misinformation, frustrations at the lack of consensus between community leaders, limited understanding of what happens during the end-of-life care leading to organ donation, and how this aligns with cultural values and preferences.

Conclusion

Implementation of the law change has not been associated to date with any change in public attitudes and preferences likely to influence consent overall or in minority ethnic groups in England. Uncommitted donors may benefit from encouragement to express their organ donation decision, and unengaged donors from attempts to address mis/information, confusion, and uncertainty. Interventions to raise the consent rate need to take account of the significant role of the family as well as wider community influences on attitudes, preferences and decision-making, particularly among certain minority (ethnic) groups.
Medical dispatchers’ experience with live video during emergency calls: a national questionnaire study
Authors: Bohnstedt-Pedersen Natascha H , Linderoth Gitte , Helios Barbara , Christensen Helle C , Thomsen Britta K , Bekker Lisbeth , Gram Jannie K B , Vaeggemose Ulla , Gehrt Tine B
Published: November 2024

Background

Telehealth has become increasingly essential in healthcare provision, also in the Prehospital Emergency Medical Services (EMS), where live video is implemented as a supplemental tool to assess and triage medical emergency calls. So far, using video for emergency calls seems beneficial for patient assessment and dispatcher-assisted first aid. However, the EMS dispatchers’ experiences with and perceptions of using video during emergency calls are largely unexplored.

Methods

In 2023, a nationwide survey study was conducted in Denmark, which is covered by five Emergency Medical Dispatch Centers. All Danish EMS dispatchers were invited to participate in the study. The survey explored the dispatchers’ experience with using video during emergency calls, the perception of their own video use, and the process of implementing video as a new tool in their working procedure. Main questions were answered on a scale from 1 to 7, where higher scores indicate more agreement.

Results

Of the 183 EMS dispatchers employed during the study period, 78% completed the survey. They found video easy to use (median = 7) and found video supportive in guidance and dispatch when the patient’s problem was unclear (median = 7), but did not find video suitable for all emergency calls and expressed that complications with the technology was a barrier for using video. The EMS dispatchers were least likely to agree that they choose not to use video due to the risk of being emotionally affected by what they might see (median = 1). When dividing the sample based on EMS dispatcher’s gender, age, seniority, and educational background, generally few differences between groups were found.

Conclusions

Live video during emergency calls is generally experienced as a useful supplemental tool by EMS dispatchers in Denmark, and the greatest self-perceived barriers for using video were not finding video suitable for all situations and the technology.
Optimized production and characterization of a thermostable cellulase from Streptomyces thermodiastaticus strain
Authors: Waheeb Mery S. , Elkhatib Walid F. , Yassien Mahmoud A. , Hassouna Nadia A.
Published: November 2024

A high cellulase-producing bacterial isolate TS4 was recovered from an Egyptian soil sample and identified using 16S rRNA gene sequencing as Streptomyces thermodiastaticus. One-factor-at-a-time (OFAT) preliminary studies were carried out to determine the key factors affecting cellulase production by S. thermodiastaticus and their optimum ranges. The initial pH of the medium, carboxymethyl cellulose (CMC), tryptone, and NaCl concentrations were further optimized using a response surface Central Composite design. Fermentation under optimized variables of initial pH 6.0, presence of CMC, tryptone, and NaCl at concentrations of 2%, 0.03%, and 0.12%, respectively, resulted in 3.24 fold increase in cellulase productivity (2023 U/L) as compared to that under basal conditions (625 U/L). Cellulase production was also improved with a 4 Kilogray (KGy) dosage of gamma radiation. In comparison to the wild-type strain under basal circumstances, S. thermodiastaticus produced 5.1 fold more cellulase after a combination of model-based optimization and gamma radiation mutation. Cellulase was partially purified using ammonium sulfate precipitation followed by dialysis. The resulting cellulase was 1.74 times purified and its specific activity was 4.21 U/mg. The molecular weight of cellulase is 63 kDa as indicated by SDS-PAGE and zymogram. Its maximum activity was achieved at 60 °C and pH 5.0. In addition, it showed outstanding thermo-tolerance as it could retain its full activity after a 12-h incubation at 90 °C.
Prestack wave-equation time migration
Authors: Yan Fan , Yang Jidong , Huang Jianping
Published: November 2024

In conventional time migration, Green’s function is commonly calculated using ray tracing, which may produce inaccurate images for complex structures with strongly lateral velocity variations. To mitigate this issue, we develop an accurate prestack wave-equation time migration method, borrowing from reverse time migration (RTM). First, a two-way acoustic wave equation is derived in the image-ray coordinate system. Then, we directly solve this equation using the finite-difference method to extrapolate source- and receiver-side wavefields, which does not require any approximation as in conventional ray-based time migration. Finally, a zero-lag crosscorrelation imaging condition is applied to generate the time migration image. In addition, we derive the dispersion relation and stability condition for the finite-difference method in the image-ray coordinate system, which provides guidance for temporal and spatial grid discretization. The perfectly matched layer boundary condition is used in the image-ray coordinate system to attenuate boundary reflections. Numerical examples of synthetic and field data verify the feasibility and adaptability of our approach for low signal-to-noise land data. In addition, after mapping the images from the time domain to the depth domain, the image results are even better than RTM results.