bluuebunny/crossref_metadata_2025 huggingface dataset:
Submodules
Authors: Metcalf Michael , Reid John , Cohen Malcolm , Bader Reinhold
Published: March 2024

Modules may be split into separate program units called submodules, which can be in separate files. Module procedures can then be split so that the interface information remains in the module, but the bodies can be placed in the submodules. A change in a submodule cannot alter an interface, and so does not cause the recompilation of program units that use the module. A submodule has access via host association to entities in the module, and may have entities of its own in addition to providing implementations of module procedures
Coarrays
Authors: Metcalf Michael , Reid John , Cohen Malcolm , Bader Reinhold
Published: March 2024

We describe the coarray programming model, which provides a simple syntactic extension from the point of view of both work distribution and data distribution. For work distribution, it adopts the Single Program Multiple Data (SPMD) programming model, with multiple “images” (usually processes) executing identical programs. For data distribution it allows each image to access data on another image with coarray syntax that is similar to Fortran array syntax. The programmer is responsible for synchronization by using special statements known as “image control” statements. These subdivide the executions on the images into segments within each of which the compiler is free to use its optimization techniques as if the image were executing on its own. Consideration is given to recovery from image failure. A collective is an intrinsic procedure in which the images collaborate for its stated task. Atomic intrinsic procedures allow different images to access or change data in turn without synchronization
The Literary Mirroring of Aboriginal Australia and the Caribbean
Authors: Moore Dashiell
Published: March 2024

Literary Mirroring challenges the structural opposition of rootedness and rootlessness through a historical and literary analysis of the connections between the ‘First and Last of the New Worlds’: the Caribbean and Australia. It explores literary and historical continuities between Australia and the Caribbean through the work of Caribbean writers such as Édouard Glissant, Wilson Harris, Sylvia Wynter, and Kamau Brathwaite, alongside Aboriginal writers like Alexis Wright, Ali Cobby Eckermann, and Lionel Fogarty. The author examines how these authors’ use of opacity and projection reimagines the inter-colonial other as a mirror image, a projection that presents readers with fresh perspectives of the movement to Indigenization in post-Independence Caribbean literature and inter-Indigenous encounters beyond the Australian nation in Aboriginal literature. By upending the simulated opposition of the Caribbean and Australia, this book offers radically new perspectives of the world generated by literary relation.
Introduction
Authors: Schoenberger Casey
Published: March 2024

The Introduction introduces principles, concepts, and historical periodization that shape the individual chapters and the work as a whole. Principles include treating speech and music as a spectrum of propositional communication and expressivity, comments on methodology of cross-cultural comparisons, and an introduction of a digital database, titled Nine Modes Manual Online. Concepts include the theory of minds as extending beyond individual brains to include material and social worlds (extended mind thesis), prediction as a key mechanism of the mind (predictive coding/processing), and the memory function of “recoding” and “decoding” “chunks” of information. A rough five-part periodization of Chinese musical-poetic history roughly corresponding with major technological and socio-political shifts is suggested. The book’s focus being on the middle three of these periods, associated stylistic tendencies of each, further detailed in chapters, are previewed: ancient “sameness,” medieval “contrast,” and late imperial “naturalness.”
Britain's Slavery Debt
Authors: Banner Michael
Published: March 2024

This book argues that Britain owes reparations to the Caribbean. The case depends on an historical and a moral claim. The historical claim is that the exploitation of generations of the islands’ inhabitants under slavery and colonialism wronged those people while enriching Britain—and crucially that, as we are the inheritors of these riches, so present generations in the Caribbean are inheritors of relative poverty. The moral claim is that where such a moral wrong has been done, moral repair or reparations are due. Racism was the enabling doctrine for slavery and colonialism, and racism is a part of its history which Britain has failed to confront. There are many familiar objections to the very idea of making reparations: ‘It was a long time ago’, ‘slavery was legal back then’, etc. There are also practical objections, especially to any monetary payment which may form part of reparations—who will pay what to whom? Taking as a starting point the £20m which the British government paid to slave owners at abolition, the book proposes a provisional sum as the starting point for negotiations with the Caribbean nations. And while the final settlement must be a matter between national governments, it is argued that other institutions, such as universities and churches, can advance the case for reparations by themselves understanding and addressing their own entanglements with enslavement and its enduring legacies.
On sexual citizenship
Authors: Langdridge Darren
Published: March 2024

This chapter outlines the central focus on sexual citizenship by locating this concept within the broader citizenship literature. This includes consideration of early theories of citizenship—liberalism, communitarianism, and civic republicanism—before moving on to consider more recent developments in citizenship theory. The concept of identity is also introduced within the context of the tension between the particular and the universal in political theory. Feminist and sexual citizenship are then introduced as attempts to work with this tension in the service of a radical programme of political transformation. Attempts to queer citizenship are discussed, and the central focus on a dialectic of ideology and utopia (as tradition and critique) is introduced.
Conservative claims for citizenship
Authors: Langdridge Darren
Published: March 2024

This chapter describes two cases that evidence how critique may reproduce tradition, effectively mimicking the language and practice of normative sexual life. The first example concerns bondage and discipline, domination and submission, sadism and masochism (BDSM) and the way that kink communities have readily embraced a therapy narrative to story their experience just at the point that the pathologizing gaze of psychiatry has receded. While recognizing that this may have value for some folk, it is argued that the embrace of a therapy narrative risks reinscribing pathology within and upon this sexual minority community. The second case concerns polyamory and how this increasingly well-known nondyadic model of relating has embraced a rather conservative narrative focused on love while claiming to offer a radical challenge to the norm. Both examples serve to demonstrate how critique may become indistinguishable from the conservative ideology it claims to overthrow.
Housing Matters
Authors: de Maaker Erik
Published: March 2024

‘Being Garo’ finds expression first and foremost in terms of relatedness. This chapter explores relational categories, and how these are experienced across distinct social domains. Proceeding from ethnographic narrative, I discuss how roles and responsibilities are shaped, in part, to fit real-life needs. Garo express relatedness with reference to matrilineal descent and affinity. Marriages that can be continued across generations provide shape to hierarchically structured residential groups. Belonging to such groups brings access to resources, the most important of which is land. While the relationships within these groups might appear immutable, over time they can be adapted and reinterpreted in accordance with changing political and economic strengths and weaknesses. Kin groups shape people’s relationships to one another, but at the same time these groups are defined by the actions of those who are part of them.
Niam, Houses, and Land
Authors: de Maaker Erik
Published: March 2024

In rural West Garo Hills, how do people relate to the environment? The traditional Garo community religion provides strategies and (ritual) techniques to live with omnipresent spirits. These integrate with religio-political structures, carried over from the precolonial era, that have been assimilated and transformed by the modern state. Focusing on Garo animism, I discuss how contemporary land relations are anchored in the past, and show how religious responsibilities and matrilineal relatedness shape residential groups. Specifying the relationships which people trace to the forest and its spirits, and the ritual techniques mandatory for the followers of the traditional Garo community religion to cultivate swidden crops, I discuss how some of these rituals take on new forms and attain new significances in a variety of contemporary contexts.
The Modernity of Garo Niam
Authors: de Maaker Erik
Published: March 2024

The last chapter revisits the main questions explored in this book. In rural West Garo Hills niam (custom) continues to be upheld, shaping moral principles that define relations among relatives which have a major impact on how land is valued, and how it can be used, while also defining many other aspects of life. As long as niam is perceived as traditional, deep-rooted, and authoritative, it can continue to underpin the relationships that people trace among one another, which influence how they share, or sometimes compete for, the resources they depend on in everyday life.
Agricultural Workers, Tenant Farmers, and the Midcentury U.S. Welfare State: A View from the Lower Mississippi Valley
Authors: Iyer Samantha
Published: March 2024

This article reconsiders what is often seen as a defining feature of the mid-twentieth-century welfare state in the United States: its exclusion of agricultural workers and tenant farmers. It shows that in the cotton-producing regions of the Mississippi Valley, agricultural workers and tenants were not excluded from the welfare state but unequally incorporated into and disciplined by it. In the absence of other government protections, agricultural workers and tenant farmers leaned heavily on food assistance in the form of federal surplus commodities and, from the mid 1960s, food stamps. These food programmes mimicked older agrarian credit relations between black workers and tenants and their employers and landlords. In this way, they affirmed hierarchies of race and class even amidst the region’s rapid transformation toward mechanized and petrochemical-based agricultural production. Civil rights protests against the workings of food distribution programmes in the lower Mississippi Valley would eventually spark a national movement that instigated a massive expansion of federal food assistance programmes by the 1970s. And yet the paternalistic form of these programmes would not be fully broken.
Balancing best practice and reality in behavioral intervention development: A survey of principal investigators funded by the National Institutes of Health
Authors: von Klinggraeff Lauren , Burkart Sarah , Pfledderer Christopher D , McLain Alexander , Armstrong Bridget , Weaver R Glenn , Beets Michael W
Published: March 2024

Preliminary studies play a prominent role in the development of large-scale behavioral interventions. Though recommendations exist to guide the execution and interpretation of preliminary studies, these assume optimal scenarios which may clash with realities faced by researchers. The purpose of this study was to explore how principal investigators (PIs) balance expectations when conducting preliminary studies. We surveyed PIs funded by the National Institutes of Health to conduct preliminary behavioral interventions between 2000 and 2020. Four hundred thirty-one PIs (19% response rate) completed the survey (November 2021 to January 2022, 72% female, mean 21 years post-terminal degree). Most PIs were aware of translational models and believed preliminary studies should precede larger trials but also believed a single preliminary study provided sufficient evidence to scale. When asked about the relative importance of preliminary efficacy (i.e. changes in outcomes) and feasibility (i.e. recruitment, acceptance/adherence) responses varied. Preliminary studies were perceived as necessary to successfully compete for research funding, but among PIs who had peer-reviewed federal-level grants applications (n = 343 [80%]), responses varied about what should be presented to secure funding. Confusion surrounding the definition of a successful, informative preliminary study poses a significant challenge when developing behavior interventions. This may be due to a mismatch between expectations surrounding preliminary studies and the realities of the research enterprise in which they are conducted. To improve the quality of preliminary studies and advance the field of behavioral interventions, additional funding opportunities, more transparent criteria in grant reviews, and additional training for grant reviewers are suggested.
Vaccine communication training using the Brief Motivational Interviewing for Maternal Immunization intervention: A PRISM implementation evaluation
Authors: Cataldi Jessica R , Brewer Sarah E , Perreira Cathryn , Fisher Mary E , Spina Christine I , Cochran Fiona , Glasgow Russell E , O’Leary Sean T
Published: March 2024

Improving clinician–patient communication can increase uptake of recommended vaccinations during pregnancy. To evaluate adaptations to and pragmatism of the brief Motivational Interviewing for Maternal Immunizations (MI4MI) intervention and to use the Practical Robust Implementation and Sustainability Model (PRISM) to describe context and implementation outcomes among clinician and staff participants. We incorporated data from study team members, clinicians and staff participants, pregnant patients at participating clinics, and patient medical records. Quantitative and qualitative data were collected using surveys, chart reviews, study team notes, interviews, and focus groups. Adaptations were evaluated using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) and pragmatism was measured with PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2). MI4MI was effective at improving participants’ vaccine communication experiences. Adoption was limited by our recruitment approach. MI4MI implementation was shaped by contextual factors and associated adaptations related to the COVID pandemic and clinic and participant characteristics. Virtual asynchronous intervention delivery had mixed effects on adoption and implementation that varied across clinics and participants. Participants expressed interest in maintaining the MI4MI intervention moving forward; however, identification of sustainability infrastructure was limited. MI4MI was evaluated to be relatively pragmatic. Contextual factors strongly shaped implementation of MI4MI. Future iterations of MI4MI should include training delivery modes and incentives that accommodate a range of participants across job roles and organizational settings. Future studies including control clinics are needed to measure effectiveness for increasing vaccination and comparing virtual versus hybrid implementation strategies.
Reassessment of ‘Gyposaurus’ sinensis Young, 1941 (Dinosauria: Sauropodomorpha) from the Early Jurassic Lufeng Basin, Yunnan Province, China
Authors: Wang Ya-Ming , Zhao Qi , You Hai-Lu
Published: March 2024

The Early Jurassic Lufeng Formation of Yunnan Province, southwestern China, has yielded a rich assemblage of early-branching sauropodomorphs. The syntype series of ‘Gyposaurus’ sinensis Young, 1941, represented by two skeletons from the Shawan Member of this formation, was the second-earliest named taxon after Lufengosaurus huenei Young, 1941. However, its taxonomic status has been debated ever since, owing to the invalidity of the genus ‘Gyposaurus’. Here, we provide a detailed redescription of the remaining syntype specimens of ‘Gyposaurus’ sinensis, including V26 and V27, which comprise almost complete postcranial skeletons. Both the unfused vertebrae and the osteohistology of the syntype specimens suggest that they are immature individuals. The morphology of the skeletons, especially that of the scapula, humerus, ilium, and femur of ‘Gyposaurus’ sinensis, is more similar to that of Lufengosaurus huenei than to that of other non-sauropodan sauropodomorphs. A phylogenetic analysis, in which ‘Gyposaurus’ sinensis and Lufengosaurus huenei were included as separate terminal taxa, recovered ‘Gyposaurus’ sinensis as part of a polytomy with Lufengosaurus huenei and Glacialisaurus, also indicating a close relationship between these taxa. Therefore, we suggest that ‘Gyposaurus’ sinensis is probably referable to a junior synonym of Lufengosaurus huenei.
Postpartum Necrotizing Myositis With Endometrial Prolapse
Authors: Li Rongyao , Fang Zheng , Zhou Qingqing , Fu Jing , Meng Ran , Cai Qiaoyun , Shen Yingli , Peng Cheng
Published: March 2024

BACKGROUND:

Postpartum necrotizing myositis is a rare condition, typically presenting as a complication after uterine artery embolization or uterine compression suturing. Uterine ischemia can cause endometrial necrosis and even myometrial necrosis, which can lead to systemic infection. If a systemic infection is not promptly and actively treated, it may pose significant risk.

CASE:

A 35-year-old patient who had undergone bilateral uterine artery ligation, modified B-Lynch suture, and multiple compression sutures due to refractory postpartum hemorrhage frequently presented to clinic after postpartum discharge due to persistent fever and vaginal discharge. A bag-like prolapse from the vagina measuring 10×5 cm, accompanied by purulent discharge, was noted 78 days postsurgery. Subsequent pelvic magnetic resonance imaging revealed a uterine basal abscess and postpartum necrotizing myositis; an emergency laparoscopic supracervical hysterectomy was performed, with postoperative pathology confirming the diagnosis. After the patient’s discharge, she was readmitted for inpatient treatment of a pelvic abscess.

CONCLUSIONS:

Although rare, postpartum necrotizing myositis should be considered in postpartum patients presenting with fever, abdominal pain, severe infection symptoms, and abnormal vaginal discharge. Culture and sensitivity testing are recommended to direct appropriate antibiotic therapy.
Furmonertinib and intrathecal pemetrexed chemotherapy rechallenges osimertinib-refractory leptomeningeal metastasis in a non-small cell lung cancer patient harboring EGFR20 R776S, C797S, and EGFR21 L858R compound EGFR mutations: a case report
Authors: Jia Guoxia , Bashir Shoaib , Ye Minting , Li Yin , Lai Mingyao , Cai Linbo , Xu Meng
Published: March 2024

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, due to the rarity of cases, the response of EGFR-TKIs in patients harboring uncommon compound EGFR mutations still needs to be determined. Here, we demonstrated the case of a 47-year-old smoker diagnosed with leptomeningeal metastasis from NSCLC and had EGFR20 R776S, C797S, and EGFR21 L858R compound mutations. He was treated with furmonertinib combined with intrathecal pemetrexed chemotherapy following progression on osimertinib, which led to clinical improvement and successfully prolonged his survival by 3 months. Regrettably, the patient eventually died from heart disease. This report provides the first reported evidence for the use of furmonertinib and intrathecal pemetrexed chemotherapy in NSCLC patients harboring EGFR R776S/C797S/L858R mutations who progressed on previous EGFR-TKIs.
Recurrent unilateral corneal edema in a 54-year-old patient after endurance sports in low temperature
Authors: Schmid Ruediger , Butros Susanne
Published: March 2024

Introduction:

Corneal edema in endurance sports at low temperatures is a rare occurrence, and few reports can be found in the literature.

Patient and Clinical Findings:

A case of unilateral corneal edema in a 54-year-old man with a history of laser in situ keratomileusis surgery, cataract surgery, and vitrectomy is presented. Recurrent episodes of corneal edema were observed during endurance cycling in temperatures below 10 °C, with complete recovery observed the next day without any treatment.

Diagnosis, Interventions, and Outcomes:

Pathophysiology and therapeutic strategies were discussed. Local administration of hyperosmolar saline lacked of any effect as did administration of acetazolamide. A protection of the affected eye by contact lens was not successful, but ski goggles could effectively prevent the corneal edema.

Conclusions:

Some single reports in the literature described roughly similar corneal findings under different conditions. A systematic evaluation of this case could reveal a fateful combination of cold temperature, physical activity, and susceptibility of the corneal endothelium. Protection from cold wind by ski goggles was found to be an effective practical approach.
What's Next for Me? Developing an 18-Month Structured Pathway to Increase New Nurse Retention
Authors: Fazzino Kirsten , Hewitt Jocelyn , Thresher Catherine , Wilder Shailyn
Published: March 2024

Because of increasing RN turnover rates on a neuroscience unit in a large teaching hospital, unit nurse leaders created a staff retention quality improvement initiative. The initiative offered a structured pathway for professional development milestones in a nurse's 1st 18 months of employment. As a consequence of their work, the unit experienced an 82% decrease in the number of RNs who left their job on the unit in the 1st year of implementation.
Predicting Early Cochlear Implant Performance: Can Cognitive Testing Help?
Authors: Schauwecker Natalie , Tamati Terrin N. , Moberly Aaron C.
Published: March 2024

Introduction:

There is significant variability in speech recognition outcomes in adults who receive cochlear implants (CIs). Little is known regarding cognitive influences on very early CI performance, during which significant neural plasticity occurs.

Methods:

Prospective study of 15 postlingually deafened adult CI candidates tested preoperatively with a battery of cognitive assessments. The mini-mental state exam (MMSE), forward digit span, Stroop measure of inhibition-concentration, and test of word reading efficiency were utilized to assess cognition. consonant-nucleus-consonant words, AZBio sentences in quiet, and AZBio sentences in noise (+10 dB SNR) were utilized to assess speech recognition at 1- and 3-months of CI use.

Results:

Performance in all speech measures at 1-month was moderately correlated with preoperative MMSE, but these correlations were not strongly correlated after correcting for multiple comparisons. There were large correlations of forward digit span with 1-month AzBio quiet (P ≤ 0.001, rho = 0.762) and AzBio noise (P ≤ 0.001, rho = 0.860), both of which were strong after correction. At 3 months, forward digit span was strongly predictive of AzBio noise (P ≤ 0.001, rho = 0.786), which was strongly correlated after correction. Changes in speech recognition scores were not correlated with preoperative cognitive test scores.

Conclusions:

Working memory capacity significantly predicted early CI sentence recognition performance in our small cohort, while other cognitive functions assessed did not. These results differ from prior studies predicting longer-term outcomes. Findings and further studies may lead to better preoperative counseling and help identify patients who require closer evaluation to ensure optimal CI performance.
Nightly Sleep Predicts Next-Morning Expectations for Stress and Positive Experiences
Authors: Wen Jin H. , Klaiber Patrick , Leger Kate A. , Hill Patrick L. , Pfund Gabrielle N. , Slavish Danica C. , DeLongis Anita , Sin Nancy L.
Published: March 2024

Objective

Abundant research has linked nightly sleep as an antecedent of daily psychosocial experiences; however, less is known about sleep’s influence on daily expectations of these experiences. Therefore, this research examined the day-to-day associations of sleep quality, duration, and efficiency with next-day expectations for stress(ors) and positive experiences, as well as whether these expectations were related to end-of-day reports of physical symptoms.

Methods

In Study 1, U.S. adults (n = 354; ages 19 to 74) completed twice-daily diaries for 10 weekdays about sleep, expectations for encountering daily stressors and positive events, and physical symptoms. In Study 2, adults in Canada (n = 246; ages 25 to 87) wore a sleep watch for 14 consecutive days and completed mobile surveys 5×/day about sleep, stressfulness and pleasantness expectations, and physical symptoms.

Results

Multilevel models indicated that self-reported sleep quality and duration, but not efficiency, were associated with lower next-day expectations for stressors (Study 1) and stressfulness (Study 2). Self-reported sleep quality (Study 1) and all sleep indices (Study 2) predicted greater next-day expectations for positive events and pleasantness, respectively. For actigraphy-assessed sleep (Study 2), only longer-than-usual actigraphic sleep duration was associated with lower stressfulness expectations, whereas both sleep duration and efficiency were positively linked with daily pleasantness expectations. Only pleasantness expectations (Study 2)—but not daily stressfulness and event expectations (Study 1)—predicted end-of-day physical symptoms.

Conclusion

Findings suggest the importance of sleep on expectations of next-day stress and positive experiences, of which may have implications for daily physical health.
Improved Disabilities of the Arm, Shoulder and Hand scores after myoelectric arm orthosis use at home in chronic stroke: A retrospective study
Authors: Chang Sarah R. , Hofland Nicole , Chen Zhengyi , Kovelman Harry , Wittenberg George F. , Naft Jonathan
Published: March 2024

Background:

Most stroke survivors have persistent upper limb impairments after completing standard clinical care. The resulting impairments can adversely affect their quality of life and ability to complete self-care tasks and remain employed, leading to increased healthcare and societal costs. A myoelectric arm orthosis can be used effectively to support the affected weak arm and increase an individual’s use of that arm.

Objective:

The study objective was to retrospectively evaluate the outcomes and clinical benefits provided by the MyoPro® orthosis in individuals 65 years and older with upper limb impairment secondary to a stroke.

Methods:

The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was administered to individuals who have chronic stroke both before and after receiving their myoelectric orthosis. A Generalized Estimating Equation model was analyzed.

Results:

After using the MyoPro, 19 individuals with chronic stroke had a mean improvement (decrease) in DASH score of 18.07, 95% CI = (−25.41, −10.72), adjusted for 8 covariates. This large change in DASH score was statistically significant and clinically meaningful as participants self-reported an improvement with engagement in functional tasks.

Conclusions:

Use of the MyoPro increases independence in functional tasks as reported by the validated DASH outcome measure for older participants with chronic stroke.
Targeting Epstein–Barr virus in multiple sclerosis: when and how?
Authors: Giovannoni Gavin
Published: March 2024

Purpose of review

Epidemiological evidence implicates Epstein–Barr virus (EBV) as the cause of multiple sclerosis (MS). However, its biological role in the pathogenesis of MS is uncertain. The article provides an overview of the role of EBV in the pathogenesis of MS and makes a case for targeting EBV as a treatment strategy for MS.

Recent findings

EBV potentially triggers autoimmunity via molecular mimicry or immune dysregulation. Another hypothesis, supported by immunological and virological data, indicates that active EBV infection via latent-lytic infection cycling within the central nervous system or periphery drives MS disease activity. This supports testing small molecule anti-EBV agents targeting both latent and lytic infection, central nervous system-penetrant B-cell therapies and EBV-targeted immunotherapies in MS. Immunotherapies may include EBV-specific cytotoxic or chimeric antigen receptors T-cells, therapeutic EBV vaccines and immune reconstitution therapies to boost endogenous EBV-targeted cytotoxic T-cell responses.

EBV is the probable cause of MS and is likely to be driving MS disease activity via latent-lytic infection cycling. There is evidence that all licensed MS disease-modifying therapies target EBV, and there is a compelling case for testing other anti-EBV strategies as potential treatments for MS.
Exploration of low-frequency allelic variants of SARS-CoV-2 genomes reveals coinfections in Mexico occurred during periods of VOCs turnover
Authors: García-López Rodrigo , Taboada Blanca , Zárate Selene , Muñoz-Medina José Esteban , Salas-Lais Angel Gustavo , Herrera-Estrella Alfredo , Boukadida Celia , Vazquez-Perez Joel Armando , Gómez-Gil Bruno , Sanchez-Flores Alejandro , Arias Carlos F.
Published: March 2024

Graphical abstract

Coinfections occurring within a single sample can be detected by exploring all mutations in a genomic set as these have full profiles commonly observed in lower prevalence.
Hox-A2 protein expression in avian jaws cartilages and muscle primordia development
Authors: Louryan Stephane M , Duterre Myriam , Vanmuylder Nathalie
Published: March 2024

Objective: to elucidate the branchial origin of the articular and the square (homology of the malleus and the incus of mammals), we used immunohistochemistry to analyse the expression of the Hox-A2 protein during cephalogenesis in chickens. Materials and methods: immunohistochemistry on paraffin sections of embryos from stage HH16 to HH40. Results: in addition to the columella (equivalent to the mammalian stapes), the joint between the articular and the quadrate bones, and the retroarticular process of the articular (homologous to the short process of the malleus) express Hox-A2, suggesting an intervention of the 2nd arch in their formation. However, we fortuitously observed very intense expression within the early muscle plate of the second arch, which then generalized to all cephalic muscles, and extended to the trunk s myotomes. In the cartilage, the presence of the protein disappeared at stage 35. Discussion and conclusion: the present results, while confirming the contribution of the second arch to the development of avian equivalents of the mammalian ear ossicles, strongly suggest that the Hox-A2 gene plays a role in muscle development, which remains to be elucidated by more sophisticated techniques.
Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease
Authors: Leonard-Duke Julie , Agro Samuel M. J. , Csordas David J. , Bruce Anthony C. , Eggertsen Taylor G. , Tavakol Tara N. , Barker Thomas H. , Bonham Catherine A. , Saucerman Jeffery J. , Taite Lakeshia J. , Peirce Shayn M.
Published: March 2024

Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular network remodeling, which leads to the expansion or regression of microvessel networks. When microvessels undergo remodeling in idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired due to loss of alveolar structures and lung function declines. Here, we integrated a multiscale computational model with independent experiments to investigate how combinations of biomechanical and biochemical cues in IPF alter cell fate decisions leading to microvascular remodeling. Our computational model predicted that extracellular matrix (ECM) stiffening reduced microvessel area, which was accompanied by physical uncoupling of endothelial cell (ECs) and pericytes, the cells that comprise microvessels. Nintedanib, an FDA-approved drug for treating IPF, was predicted to further potentiate microvessel regression by decreasing the percentage of quiescent pericytes while increasing the percentage of pericytes undergoing pericyte-myofibroblast transition (PMT) in high ECM stiffnesses. Importantly, the model suggested that YAP/TAZ inhibition may overcome the deleterious effects of nintedanib by promoting EC-pericyte coupling and maintaining microvessel homeostasis. Overall, our combination of computational and experimental modeling can explain how cell decisions affect tissue changes during disease and in response to treatments.
Conformal prediction of molecule-induced cancer cell growth inhibition challenged by strong distribution shifts
Authors: Hernandez-Hernandez Saiveth , Guo Qianrong , Ballester Pedro J.
Published: March 2024

The drug discovery process often employs phenotypic and target-based virtual screening to identify potential drug candidates. Despite the longstanding dominance of target-based approaches, phenotypic virtual screening is undergoing a resurgence due to its potential being now better understood. In the context of cancer cell lines, a well-established experimental system for phenotypic screens, molecules are tested to identify their whole-cell activity, as summarized by their half-maximal inhibitory concentrations. Machine learning has emerged as a potent tool for computationally guiding such screens, yet important research gaps persist. Consequently, this study focuses on the application of Conformal Prediction (CP) to predict the activities of novel molecules on specific cancer cell lines. Two CP models were constructed and evaluated on each cell line, resulting in a total of 120 performance evaluations (60 cell lines x 2 CP models) per training-test partition. From this comprehensive evaluation, we concluded that, regardless of the cell line or model, novel molecules with smaller CP-calculated confidence intervals tend to have smaller predicted errors once measured activities are revealed. It was also possible to anticipate the activities of dissimilar test molecules across 50 or more cell lines. These outcomes demonstrate the robust efficacy that CP models can achieve in realistic and challenging scenarios, thereby providing valuable insights for enhancing decision-making processes in drug discovery.
Optimized CART Cell Therapy for Metastatic Aggressive Thyroid Cancer
Authors: Gleba Justyna J. , Siegler Elizabeth L. , Manriquez-Roman Claudia , Huynh Truc N. , Mai Long K. , Miller James L. , Miller Erin E. , Pawlush Matthew L. , Demirer Aylin Alasonyalilar , Kimball Brooke L. , Tapper Erin E. , Sakemura R. Leo , Stewart Carli M. , Can Ismail , Sirpilla Olivia L. , Feigin Jennifer M. , Yun Kun , Gutierrez Ruiz Omar L. , Xia Hong , Torghabeh Mehrdad Hefazi , Schick Kendall J. , Ogbodo Ekene J. , Olivier Gloria , Qiu Yushi , Tun Han W. , Smallridge Robert C. , Zubair Abba , Copland John A. , Kenderian Saad S.
Published: March 2024

Most thyroid cancer deaths are attributed to a subset of poorly differentiated, metastatic tumors. To improve treatment options for these aggressive thyroid cancers, we developed a novel thyroid-stimulating hormone receptor (TSHR)-targeted chimeric antigen receptor T (CART) cell therapy, which demonstrated antigen-specific activation and antitumor efficacy against TSHR-overexpressing cell linesin vitroandin vivo. However, de- differentiated thyroid cancers downregulate TSHR. We therefore developed a potent treatment strategy by combining our novel TSHR-CART cells with mitogen-activated protein kinase (MAPK) inhibitors, which redifferentiate thyroid tumors and upregulate TSHR expression. In patient-derived anaplastic thyroid cancer xenografts, combination therapy of TSHR-CART cells and MAPK inhibitors led to increased TSHR expression on the tumor tissue and significantly enhanced antitumor efficacy and prolonged survival compared to TSHR- CART monotherapy.

STATEMENT OF SIGNIFICANCE

Poor target selection and antigen escape limit CART cell efficacy in solid tumors. We developed TSHR-CART cells to treat differentiated thyroid cancers but observed TSHR downregulation in dedifferentiated thyroid cancers. We found that MAPK inhibitors restored TSHR expression and sensitized these cancers to TSHR- CART cell therapy.
“Multiplexed screen identifies aPseudomonas aeruginosa-specific small molecule targeting the outer membrane protein OprH and its interaction with LPS”
Authors: Poulsen Bradley E. , Warrier Thulasi , Barkho Sulyman , Bagnall Josephine , Romano Keith P. , White Tiantian , Yu Xiao , Kawate Tomohiko , Nguyen Phuong H. , Raines Kyra , Ferrara Kristina , Golas Aaron , Fitzgerald Michael , Boeszoermenyi Andras , Kaushik Virendar , Serrano-Wu Michael , Shoresh Noam , Hung Deborah T.
Published: March 2024

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly againstPseudomonas aeruginosa, a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) ofP. aeruginosacombined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging. We adapted PROSPECT1, a target-based, whole-cell screening strategy, to discover small molecule probes that killP. aeruginosamutants depleted for essential proteins localized at the OM. We identified BRD1401, a small molecule that has specific activity against aP. aeruginosamutant depleted for the essential lipoprotein, OprL. Genetic and chemical biological studies identified that BRD1401 acts by targeting the OM β-barrel protein OprH to disrupt its interaction with LPS and increase membrane fluidity. Studies with BRD1401 also revealed an interaction between OprL and OprH, directly linking the OM with peptidoglycan. Thus, a whole-cell, multiplexed screen can identify species-specific chemical probes to reveal novel pathogen biology.
Protective function ofex vivoexpanded CD8 T cells in a mouse model of adoptive therapy for cytomegalovirus infection depends on integrin beta 1 but not CXCR3, CTLA4, or PD-1 expression
Authors: Liu Xiaokun , Jauregui Rodrigo Gutierrez , Lueder Yvonne , Halle Stephan , Ospina-Quintero Laura , Ritter Christiane , Schimrock Anja , Willenzon Stefanie , Janssen Anika , Wagner Karen , Messerle Martin , Bošnjak Berislav , Förster Reinhold
Published: March 2024

The adoptive transfer of virus-specific T cells (VSTs) represents a therapeutic option for viral infection treatment in immunocompromised patients. Before administration,ex vivoculture enables VST expansion. However, it is unclear howex vivoexpansion affects the circulation, homing, and intra-tissue migration of administered VSTs. We established a model of VST immunotherapy of acute cytomegalovirus infection using adoptive transfer ofex vivoexpanded OT-I CD8 T cells (recognizing SIINFEKL peptide) intoRag2-/-mice infected with murine cytomegalovirus (MCMV) encoding for the SIINFEKL peptide.Ex vivoexpansion induced an effector T cell phenotype and affected the expression of integrins and chemokine receptors. CRISPR/Cas9-mediated gene deletions enabled us to address the role of selected genes in the homing of VSTs following intravenous administration. We found that deletion ofItgb1, encoding for integrin beta 1, prevented OT-I cells from entering infected organs and drastically reduced their number in blood, suggesting that adoptively transferred VSTs primarily expand in the infected tissues. In contrast,Cxcr3-/-OT-I cells provided equal protection as theirCxcr3+/+counterparts, indicating that this chemokine receptor does not contribute to VST entry into infected organs. Further,Pdcd1andCtla4deletion did not impair the transferred OT-I cells’ ability to protect mice from MCMV, arguing against quick exhaustion of VSTs with an effector T cell phenotype. Together, these data indicate thatex vivoexpansion affects migration and activation properties of VSTs and suggest that future clinical evaluation of adoptive T cell therapy efficacy should include homing molecule expression assessment.
Suppressive effects of oroxylin A on intracellular proliferation ofToxoplasma gondiivia host cell ERK phosphorylation inhibition
Authors: Zhang Ziyue Z , Norose Kazumi , Shinjyo Noriko , Lin Xiaoxia X , Suganami Akiko , Tamura Yutaka , Sakamoto Hirokazu , Hikosaka Kenji
Published: March 2024

Toxoplasma gondiiposes a significant threat to immunocompromised patients, resulting in high mortality rates. Considering the side effects of anti-Toxoplasmadrugs, we focused on a potential candidate, oroxylin A (OA), a common component extracted fromAstragalus membranaceusandScutellaria baicalensiswhich suppressed the growth ofT. gondii in vitroandin vivo.Our result demonstrated that OA suppressedT. gondiiintracellular proliferation and downregulated phosphorylation of ERK1/2 ofT. gondii-infected host cells very similar to the MEK1 specific inhibitor PD98059. Ourin silicoanalysis showed that OA interacts sufficiently with the mammalian MEK1 region where established MEK1 inhibitors like PD98059 and trametinib bind. Moreover, OA improved the survival rate inT. gondii-infected mice. This study proposes that host MEK1 is a novel potential target for anti-Toxoplasmadrugs with a new mechanism of action.
Cardiovascular disease risk score derivation and validation in Abu Dhabi, United Arab Emirates. Retrospective Cohort Study
Authors: Baynouna AlKetbi Latifa , Nagelkerke Nico , Humaid Ahmed , AlAlawi Noura , AlKetbi Rudina , Aleissaee Hamda , AlShamsi Noura , Abdulbaqi Hanan , Fahmawee Toqa , AlHashaikeh Basil , AlDobaee Muna , AlShamsi Mariam , AlAhbabi Nayla , AlAzeezi AlYazia , Shuaib Fatima , Alnuaimi Jawaher , Mahmoud Esraa , AlDhaheri Alreem , AlMansoori Mohammed , AlKalbani Sanaa , AlDerie Wesayef , Saeed Ekram , AlMarzooqi Nouf , AlHassani Ahmed , AlAhmadi Amira , Sahyoni Mohammed , AlFahmawi Farah , AlAlawi Ali , Sahalu Yusra , AYahyaee Aysha , AlAnsari Zinab , Doucoure Khadija , Ashoor Rawan , AlShamsi Reem , AlAzeezi Maha , AlMeqbaali Fatima , Yahya Noor , AlAlawi Shamma , AlKetbi Fatima
Published: March 2024

Abstract

Cardiovascular disease (CVD) risk assessment is key to rational decision-making in primary prevention. The CVD risk depends on dynamic factors requiring continuous equation updates.

Design

The Abu Dhabi Risk Study (ADRS) is the first and longest-duration retrospective cohort study in Abu Dhabi and the United Arab Emirates (UAE), aiming to develop 10-year risk prediction equations for CAD, stroke, and ASCVD (Atherosclerotic Cardiovascular Disease, combining CAD and stroke) and validate international risk equations.

Method

The included 8699 subjects are participants of the national cardiovascular screening program of 2011-2013 with an average follow-up of 9.2 years. They were assessed retrospectively in 2023 for health outcomes. The validation cohort, 2554 subjects, is another community-based screening program done in Abu Dhabi in the period from 2016 and 2017. With an average follow-up of 6.67 years.

Results

Of 8504 who were ASCVD-free, 250 had new coronary artery events. Identified risk factors for ASCVD in this population were the conventional risk factors such as age, gender, smoking, high cholesterol/HDL ratio, and diabetes diagnosis, in addition to low vitamin D level, and low glomerular filtration rate (GFR) levels.

Three ADRS prediction models were derived from Cox regression. The ADRS-CAD had a C- statistic of 0.899 compared to 0.828 of FRS (Framingham score) in the same population.

ADRS-Stroke had a c-statistic of 0.904. The ADRS-ASCVD had a c-statistic of 0.898 compared to 0.891 of PCE (pooled cohort equations) and 0.825 of FRS-CVD.

Applying the developed formulas to the validation cohort showed good predictability of CAD and ASCVD events with an ASCVD c-statistic of 0.825, for CAD the c-statistic was 0.799, and for stroke, it was 0.761. The PCE showed similar performance in this cohort with a c-statistic for ASCVD of 0.824.

Conclusion

This study demonstrated the value of tailoring risk assessments to local populations and healthcare contexts.
Effects of context changes on memory reactivation
Authors: Özdemir Şahcan , Şentürk Yağmur Damla , Ünver Nursima , Demircan Can , Olivers Christian N.L. , Egner Tobias , Günseli Eren
Published: March 2024

While the influence of context on long-term memory (LTM) is well-documented, its effects on the interaction between working memory (WM) and LTM remain less understood. In this study, we explored these interactions using a delayed match-to-sample task, where participants (6 Male, 16 Female) encountered the same target object across six consecutive trials, facilitating the transition from WM to LTM. During half of these target repetitions, the background color changed. We measured the WM storage of the target using the contralateral delay activity (CDA) in electroencephalography (EEG). Our results reveal that task-irrelevant context changes trigger the reactivation of long-term memories in WM. This reactivation may be attributed to content-context binding in WM and hippocampal pattern separation.

Significance Statement

Understanding the mechanisms of memory updating in response to changing contexts is vital because context plays a pivotal role in shaping long-term memories. This study demonstrates, for the first time, that an irrelevant context change triggers the reactivation of learned memories in visual working memory. This observation underscores the importance of multi-memory interactions during context updating. Challenging traditional memory models that postulate mandatory reactivation of long-term memories upon each use, our results instead reveal a selective reactivation process, especially during transitions to new environments. This finding elucidates the adaptive nature of memories and enhances our understanding of memory storage and retrieval processes.
Convergent effects of different anesthetics on changes in phase alignment of cortical oscillations
Authors: Bardon Alexandra G. , Ballesteros Jesus J. , Brincat Scott L. , Roy Jefferson E. , Mahnke Meredith K. , Ishizawa Yumiko , Brown Emery N. , Miller Earl K.
Published: March 2024

Many anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how anesthetic doses of ketamine and dexmedetomidine affected oscillations in the prefrontal cortex of nonhuman primates. Both anesthetics caused increases in phase locking in the ventrolateral and dorsolateral prefrontal cortex, within and across hemispheres. However, the nature of the phase locking varied. Activity in different subregions within a hemisphere became more anti-phase with both drugs. Local analyses within a region suggested that this finding could be explained by broad cortical distance-based effects, such as large traveling waves. By contrast, homologous areas across hemispheres became more in-phase. Our results suggest that both anesthetics induce strong patterns of cortical phase alignment that are markedly different from those in the awake state, and that these patterns may be a common feature driving loss of responsiveness from different anesthetic drugs.