bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 92: Assessment of an in vitro potency assay for evaluation of immune cell-mediated cytotoxicity using the Omni Pro 12 automated imaging platform
Authors: Sullivan Denise , Stemkens Lieke , Thijssen Inge , Meiler Svenja , Califano Danielle , Chvatal Stacie , Millard Daniel
Published: March 2024

The development of immunotherapies relies on the use of in vitro potency assays—which are key for understanding complex interactions between immune cells and cancer cells. Immune effector T-cells are a promising cancer therapy due to their innate cytotoxicity. In particular, CAR T-cell therapy uses genetically engineered T-cells that express a chimeric antigen receptor that binds to a specific antigen on tumor cells. Assessing the efficacy and potency of CAR T-cell therapies in vitro and at high throughputs is vital for the preclinical development of these promising therapies. Here, we describe an in vitro potency assay that uses an automated imaging platform to quantify immune cell-mediated cytotoxicity of cancer target cells by immune effector cells. A GFP fluorescent and HER-2 expressing lung cancer cell line, A549, was seeded into a 96-well cell culture plate. Then, HER-2 CAR T-cells were added at 24 hours post target cell seeding at various E:T ratios (1:10, 1:5, 1:2, 1:1, and 5:1). Fluorescent images of the target cells were captured every 6 hours by the Omni Pro 12, an automated, high-throughput, live-cell analysis platform designed for continuous multi-well imaging inside an incubator. Automated image analysis was performed using the Confluency Module in the Axion Portal to view attachment and proliferation and quantify cytolysis of fluorescent A549 target cells. Percent cytolysis of the target cells was calculated by comparing the green fluorescent confluency of treated wells to no treatment control wells. A549-GFP cells showed a dose-dependent decrease in confluency over time that correlated with increasing amounts of CAR T-cells. At 92 hours post HER-2 CAR T-cell addition, the 5:1 ET group demonstrated approximately 91.8% +/- 2.0% cytolysis of A549-GFP cells, while the 1:10 group demonstrated approximately 69.2% +/- 3.0% cytolysis. Future work will evaluate differences in CAR T-cell potency when co-cultured with target cells that express different levels of HER-2. Overall, the Omni Pro 12 platform enables continuous quantification of the potency and kinetics of immune cell-mediated cytolysis.

Citation Format: Denise Sullivan, Lieke Stemkens, Inge Thijssen, Svenja Meiler, Danielle Califano, Stacie Chvatal, Daniel Millard. Assessment of an in vitro potency assay for evaluation of immune cell-mediated cytotoxicity using the Omni Pro 12 automated imaging platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 92.
Abstract 933: Single-cell inference and validation of heterogeneous drug sensitivity in cholangiocarcinoma reveals dacinostat as novel therapeutic candidate
Authors: Obradovic Aleksandar , Tomassoni Lorenzo , Yu Daoqi , Drake Charles G. , Dela Cruz FIlemon , Kung Andrew , Califano Andrea
Published: March 2024

Cholangiocarcinoma is a rare, aggressive malignancy with limited treatment options, due to a paucity of actionable mutations and low response to immune checkpoint inhibitors. Furthermore, its extreme heterogeneity prevents identification of actionable dependencies from bulk-tissue profiles, such that transformed cells themselves represent as little as 10% of cells comprising the complex micro-environment of these tumors. To address these challenges, we introduce a highly generalizable, single-cell framework for the mechanism-based prioritization of drugs to treat rare, heterogeneous tumors. Analysis of tumor cells isolated by single-cell RNA-Sequencing across six patients and two independent data sources using protein activity inference has revealed three molecularly distinct subphenotypes of cholangiocarcinoma cells, present to varying degrees across patients but with highly conserved proteomic signatures, and predicted to be sensitive to four drugs by regulatory network analysis. A seventh independent patient recapitulated these phenotypes, and drug sensitivity predictions at single-cell level for this patient were validated in low-passage, patient-derived xenografts from the same patient, which confirmed tumor growth rate control by two of these drugs (plicamycin and dacinostat) and further validated predicted subpopulation-specific effects, such that dacinostat alone inhibited tumor growth across all three tumor subphenotypes, while plicamycin preferentially inhibited some but not all, allowing the remaining phenotypes to reconstitute a treatment-resistant tumor. This approach suggests dacinostat as a promising candidate for follow-up clinical trials in cholangiocarcinoma, either alone or in combination with current standard-of-care chemotherapies, and is highly generalizable to elucidate complementary dependencies of other aggressive, heterogeneous tumors.

Citation Format: Aleksandar Obradovic, Lorenzo Tomassoni, Daoqi Yu, Charles G. Drake, FIlemon Dela Cruz, Andrew Kung, Andrea Califano. Single-cell inference and validation of heterogeneous drug sensitivity in cholangiocarcinoma reveals dacinostat as novel therapeutic candidate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 933.
Abstract 938: Screening the entire kinase-directed, FDA-approved pharmacopeia against the largest collection of wild-type and mutant kinases reveals many opportunities for drug repurposing and targeted therapy
Authors: Loch Christian M. , Liang Shuguang , Wu Jianghong , Eason Mia , Goupil Alison , Acinapura Anthony , Purcell Jamie , Dominguez Maia
Published: March 2024

We sought to screen all FDA approved, cancer-indicated, kinase targeting drugs using the gold standard radiometric biochemical activity assay (HotSpot) against the largest collection of kinases in the world (>100 drugs against 735 total kinases including 395 wild type and 340 mutants). Virtually every drug examined exhibits polypharmacology inhibiting many kinases. Rarely does the intended target represent the greatest inhibition observed from a drug. Furthermore, most drugs inhibit a select group of mutant kinases, including especially mutants of kinases distinct from the intended target. Within a given kinase, each cancer-identified mutation is often as distinct as the different wild-type kinases are from each other, in terms of inhibition profile. Considering mutants, then, the cancer-relevant druggable kinome is many thousand distinct targets, not 518 “plus a few”. Exposing this reality is a first step towards developing all the therapeutic tools necessary to ultimately defeat cancer. Here, we reveal vast and specific repurposing opportunities among the existing pharmacopeia for tumors that are driven by kinases not previously recognized as targets for certain drugs, and for tumors that have become chemotherapy-resistant through mutation of specific kinases. The most exciting and clinically relevant opportunities were confirmed in cell-based assays, results of which will also be presented.

Citation Format: Christian M. Loch, Shuguang Liang, Jianghong Wu, Mia Eason, Alison Goupil, Anthony Acinapura, Jamie Purcell, Maia Dominguez. Screening the entire kinase-directed, FDA-approved pharmacopeia against the largest collection of wild-type and mutant kinases reveals many opportunities for drug repurposing and targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 938.
Abstract 943: Identification and validation of unusual drug combinations identified from combination databases
Authors: Grant Rainer , Pinheiro Marco , Roska Rachel Weller , Felix Robert
Published: March 2024

There is a noted trend in the identification and subsequent approval of rational drug combinations to treat various diseases, particularly cancer. When applied in a clinical setting, synergistic combinations can have significant benefits including improved patient response and avoiding or overcoming drug resistance. Although multiple strategies have been successfully implemented to identify rational drug combinations, extensive validation is initially required to confirm a combination as synergistic. The existence and growing use of web-based repositories containing comprehensive drug combination data is a key resource and can be a valuable starting point for identifying synergistic combinations. However, are synergistic combinations from these datasets expected or rational and can they be validated experimentally? By mining available drug combinations from the DrugCombo database, we wanted to identify unusual drug combinations reported as synergistic and experimentally validate these with dose-response assays. In addition, we set out to establish if cytokines could be used as an inhibition biomarker to easily assess synergy. We found multiple unexpected synergies including a predicted synergy between the JAK1/2 inhibitor Ruxolitinib with Maraviroc, a CCR5 antagonist, or Levetiracetam, an SV2A binding anti-epileptic reported in the lymphoma cell line, L-1236. Experimentally, these predicted synergies could not be validated. In the context of synergistic drug combinations, this work shows that experimental validation is crucial, particularly for combinations with uncertain biological mechanisms.

Citation Format: Rainer Grant, Marco Pinheiro, Rachel Weller Roska, Robert Felix. Identification and validation of unusual drug combinations identified from combination databases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 943.
Abstract 950: Functional characterization of atypical somatic variants in the Gundersen Precision Oncology Cohort
Authors: Feiszt Peter , Kenny Paraic A.
Published: March 2024

The generation and widespread sharing of large somatic mutation datasets has revolutionized our understanding of genetic mechanisms driving cancer initiation and progression. For well-understood mutations, this has created the opportunity for individualized therapeutic intervention in a wide range of malignancies. Beyond these well-characterized mutations, there exists a wide range of alterations that remain poorly understood and which require some kind of functional genomics analysis to determine whether such patients are eligible for the targeted therapy used for more typical mutations in that gene, whether these alterations are passenger mutations that don’t affect throughput on the associated signaling pathway, or reflect another more nuanced phenomenon.

Whether using ectopic overexpression in cell lines or generation of genetically modified mice, addressing this problem at scale using functional genomics approaches is challenging. A key limitation is the absence of the original tissue context in which that variant co-evolved with other genetic alterations as well as data on the clinical response of the patient to successive lines of therapy. This can be addressed, in part, by the banking of tissue from patient cohorts who have had comprehensive genomic profiling as part of their routine clinical care.

The Gundersen Precision Oncology Cohort is a growing dataset of FFPE specimens and longitudinal clinical data from more than 750 patients who have had comprehensive cancer genome profiling using assays from a wide range of diagnostic companies. We use this resource for biomarker discovery and functional classification of many atypical cancer variants. Current subgroups include atypical point mutations in BRAF, ERBB2 and ERBB3, as well as fusions affecting BRAF, PIK3CA and ROS1. We present examples illustrating the value of this approach for classification of variants detected in a range of tumor types.

Citation Format: Peter Feiszt, Paraic A. Kenny. Functional characterization of atypical somatic variants in the Gundersen Precision Oncology Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 950.
Table S1 from D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation
Authors: Pianka Sean T. , Li Tie , Prins Terry J. , Eldred Blaine S.C. , Kevan Bryan M. , Liang Haowen , Zapanta Rinonos Serendipity , Kornblum Harley I. , Nathanson David A. , Pellegrini Matteo , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy F. , Lai Albert
Published: March 2024

Glioma Patient Sample Characteristics
Genetic Variability of SOX10-Related Disorders within an Italian Family: Straddling the Line between Kallmann and Waardenburg Syndrome
Authors: Graziani Ludovico , Carriero Miriam Lucia , Pozzi Flavio , Minotti Chiara , Andreadi Aikaterini , Bellia Alfonso , Ruta Rosario , Bengala Mario , Novelli Antonio , Lauro Davide , Novelli Giuseppe
Published: March 2024

Introduction: Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that most often manifests hypogonadotropic hypogonadism (HH) and hypo-/anosmia due to early embryonic impairment in the migration of gonadotropin-releasing hormone neurons. SOX10 (SRY-Box 10; MIM*602229), a key transcriptional activator involved in the development of neural crest cells, has been associated with KS and is identified as one of the causative genes of Waardenburg syndrome (WS). Case Presentation: A 28-year-old female patient, who was clinically diagnosed with KS in her childhood, presented with HH and anosmia, mild bilateral sensorineural hearing loss (SNHL), and pigmentation abnormalities. Next-generation sequencing analysis detected a missense heterozygous SOX10 pathogenic variant (NM_006941.4:c.506C>T) in the proposita and in her mother, whose phenotype included exclusively anosmia and hypopigmented skin patches. The same variant has been described by Pingault et al. [Clin Genet. 2015;88(4):352–9] in a patient with apparently isolated bilateral severe SNHL. Conclusion: Our finding substantiates the extreme phenotypic variability of SOX10-related disorders, which range from classical KS and/or WS to contracted endophenotypes that could share a common pathway in the development of neural crest cells and highlights the need for careful evaluation and long-term follow-up of SOX10 patients, with special focus on atypical/additional and/or late-onset phenotypic traits.
A Novel ZBTB20 Variant in a Patient with Primrose Syndrome: A Rare Clinical Entity with Distinctive Features
Authors: Soğukpınar Merve , Karaosmanoğlu Beren , Utine Gülen Eda , Boduroğlu Koray , Şimşek-Kiper Pelin Özlem
Published: March 2024

Introduction: Primrose syndrome (PS; MIM #259050) is a rare autosomal dominant genetic condition characterized by macrocephaly with or without tall stature, hypotonia, moderate to severe intellectual disability (ID) with delay in expressive speech development, behavioral abnormalities, and a recognizable facial phenotype including deep set eyes, ptosis, narrow and frequently downslanting palpebral fissures, and depressed nasal bridge. PS is caused by a heterozygous pathogenic variant in ZBTB20 (MIM #606025) on chromosome 3q13. Among other characteristic findings are ocular abnormalities, hearing loss, calcification of the external ear cartilage, nonspecific brain magnetic resonance imaging findings, and cryptorchidism. Adults may exhibit joint contractures, distal muscle wasting, sparse body hair, cataract, and disturbed glucose metabolism as well. The majority of affected individuals have typically been adults until recently since the phenotype becomes more recognizable in time. Case Presentation: In this study, we report on a 14-month-old girl who presented with neurodevelopmental findings, facial features, and hearing loss. The glucose metabolism was normal, and muscle atrophy, joint contractures, and external ear cartilage calcification were yet hitherto not evident. A novel de novo missense variant in ZBTB20 was identified with the aid of exome sequencing. Conclusion: PS is a rare clinical entity with various recognizable features, yet the phenotype may be indistinguishable from other neurodevelopmental disorders. Exome sequencing is a useful diagnostic tool especially in patients with no specific diagnosis despite detailed examinations and imaging studies.
Algumas palavras sobre found footage
Authors: Kubelka Peter
Published: March 2024

Para um montador TODA metragem filmada é metragem filmada ENCONTRADA. é o montador quem está REALIZANDO o filme. realizar significa (A)JARDINAR.
O homem dotado de imagem: reempregos críticos segundo Peter Tscherkassky, Jean-Luc Godard, Andrei Ujică e Marylène Negro
Authors: Brenez Nicole
Published: March 2024

A história das artes (literatura, arquitetura, música, pintura, cinema)  é massivamente constituída por reempregos e contrassensos. O século XX viu se desenvolver uma cultura do reemprego de intenção crítica, seja ela de ordem analítica, polêmica ou simplesmente reflexiva. À medida que as imagens se acumularam e as práticas, suportes e modos de difusão se multiplicaram, as iniciativas analíticas e críticas também se desenvolveram.
O roteiro de sobras
Authors: Favre Michel
Published: March 2024

O entusiasmo geral que acompanhou a exposição do l’Elysée e a recente publicação de um livro, Fotoformas, contribuíram sem dúvida para a retomada, pelo artista, de um trabalho em fotografia. Além disso, em perfeita adequação com suas limitações físicas, decorrentes das inúmeras isquemias cerebrais que o deixaram com uma parte do corpo inválida, Geraldo conseguia desenvolver um trabalho artístico que lhe fosse possível: dirigia uma assistente que, segundo suas instruções, decupava negativos de família. O artista buscava esse material numa gaveta ao alcance da mão a partir da poltrona na qual passava a maior parte do tempo. Foi assim que, à sua maneira, ele se apropriou dos conceitos de restos, como se, no crepúsculo da vida, pudesse reciclar tudo, incluindo as lembranças da felicidade familiar. Iniciada em segredo em 1996, a série Sobras nascia, assim, do seu desejo, sempre presente, de criar apesar dos imprevistos da vida.
Contribuições para a documentação técnica do edifício Copan: caracterização do embasamento
Authors: Bernardo Daniel Farias da Silva , Oliveira Fabiana Lopes de
Published: March 2024

This article presents the results of an extensive documentary research aimed at discovering and documenting constructive aspects of the substructure of the Copan Building. The data acquisition process was divided into documentary research, geometric survey, and visual inspection. Primary sources retrieved from the archives of the Faculty of Architecture and Urbanism of the University of São Paulo (FAUUSP), the São Paulo Institute of Technological Research (IPT), and the Copan Building condominium itself were used. As a result, a technical and historical description of the building’s construction aspects, with a focus on the foundation, is presented The documentation undertaken helped to understand and, primarily, confirm certain constructive characteristics of the building that often appeared contradictory in the literature or had not been properly recorded
Sensory modality and information domain contribute jointly to dual-task interference between working memory and perceptual processing
Authors: Fleming Justin T. , Njoroge J. Michelle , Noyce Abigail L. , Perrachione Tyler K. , Shinn-Cunningham Barbara G.
Published: March 2024

Making sense of our environment requires us to extract temporal and spatial information from multiple sensory modalities, particularly audition and vision. Often, we must hold this sensory information in working memory (WM) to guide future actions, while simultaneously processing new sensory inputs as they arise. However, these processes of WM maintenance and perceptual processing can interfere with one another when the tasks rely on similar cognitive resources. fMRI studies have uncovered attention and WM networks that are specialized for either auditory-temporal or visual-spatial processing; the functional specialization of these networks makes specific predictions about patterns of interference between perceptual processing and WM. Specifically, we hypothesized that dual-task interference should increase when the tasks share a common sensory modality, a common information domain (temporal vs. spatial processing), or both. To test these predictions, we asked participants to store temporal or spatial information about auditory or visual stimuli in WM. On some trials, participants also performed an intervening auditory task, which was either temporal or spatial, during WM retention. Errors on WM recall and perceptual judgment tasks both generally increased when the tasks relied on shared modality- and domain-biased resources, with maximal interference when both tasks were auditory-temporal. Pupil dilations were also larger and started earlier when both tasks were auditory-temporal, indicating an increase in cognitive effort to overcome the interference. Event-related potentials (ERPs) and alpha-band oscillatory activity revealed neural signatures of domain-based interference even when the tasks were presented in different sensory modalities, when behavioral differences were masked by ceiling effects. These results demonstrate that sensory modality and information domain jointly affect how task information is represented in WM, consistent with past work demonstrating how tasks engage complementary auditory-temporal and visual-spatial cognitive control networks.
Effect of Sarcopenia on the Prognosis of Clinical Outcomes in Patients With Hepatocellular Carcinoma After Hepatic Resection
Authors: Polvieng Thanatchawan , Hongjinda Sermsak , Thienhiran Anuparp , Burasakarn Pipit , Fuengfoo Pusit
Published: March 2024

Background

We aimed to study the prognostic impact of sarcopenia on overall survival (OS), disease-free survival (DFS), and postoperative outcomes among patients with Hepatocellular carcinoma (HCC) who underwent curative hepatic resection.

Methods

Data were collected retrospectively from patients with HCC underwent curative hepatic resection and preoperative abdominal computed tomography (CT) at our institution between January 2010 and December 2020. Sarcopenia was evaluated by the skeletal muscle mass at the inferior direction of the third-lumbar-vertebra (L3) cross-sectional area based on preoperative CT imaging using software analysis. Cutoff values for skeletal muscle index (SMI) were 43.75 and 41.10 cm2/m2 for males and females. The patients were classified into sarcopenia and nonsarcopenia groups. The association between preoperative sarcopenia and clinicopathological factors, impact of sarcopenia on survival, and postoperative outcomes were analyzed.

Results

Sarcopenia was present in 39 of 83 (47.0%) patients who underwent curative hepatic resection for HCC and was significantly correlated with lower SMI, lower serum albumin levels, higher intraoperative blood loss, higher postoperative complications, and longer hospital stay. The 5-year OS was significantly lower in sarcopenic patients than in nonsarcopenic patients (58.2% vs 83.6%; P = .006), but the 5-year DFS was not significantly different between the 2 groups. Multivariate analysis revealed that sarcopenia was a significant risk factor for poor OS (HR 4.728; 95% CI, 1.458-15.329; P = .010).

Conclusion

Sarcopenia was identified as a prognostic factor for poor OS after hepatic resection, and major postoperative complications were more frequent in sarcopenia. Early sarcopenia detection and management may improve OS and clinical outcomes in postoperative HCC.
Two-Stage Liver Transplantation and Tricuspid Valve Replacement After Blunt Trauma in a Pediatric Patient
Authors: Wallace Marshall W. , Kastenberg Zachary J. , Swendiman Robert A. , Eckhauser Aaron W. , Rodriguez-Davalos Manuel , Russell Katie W.
Published: March 2024

In cases of uncontrollable hepatic hemorrhage or acute hepatic failure after trauma, liver transplantation can be a lifesaving procedure. Traumatic tricuspid valve injuries are rare, and symptoms can range from indolent to acute right heart failure. When concomitant, traumatic liver transplant and tricuspid injuries have significant physiologic interplay and management implications. We present a 14-year-old male injured in an all-terrain vehicle accident, who sustained a devastating disruption of the common bile duct and celiac artery injury, leading to acute hepatic failure, necessitating a two-stage liver transplantation. He was subsequently found to have a severe traumatic tricuspid injury, which required tricuspid valve replacement. At 4 years post-injury, he is without major complications. This is the first case presentation of the cooccurrence of these complex pathologies. Importantly, we demonstrate the complex decision-making surrounding traumatic liver transplantation and timing of subsequent tricuspid valve repair, weighing the complex interplay of these 2 pathologies.
Biblical interpretation at the Ottawa convoy occupation
Authors: Mitchell Christine
Published: March 2024

In this contribution, Christine Mitchell analyses some of the biblical texts and imagery that appeared in photographs, social media and other formats during and after the ‘Freedom Convoy’ of January–February 2022. She discusses white Christian nationalism, Canadian contexts and interpretations of biblical texts, and demonstrates that a kind of ‘plain reading’ of Christian scripture blended with Canadian symbolism gave a religious framework to the convoy.
How narcissism, promotion criteria, and empowering leadership jointly influence creativity through diverse information searching: An expectancy perspective
Authors: Liu Zhiqiang , Zhou Kong , Wang Jie
Published: March 2024

While narcissism is commonly regarded as a dark personality trait associated with many negative outcomes, it also carries potential benefits. How to suppress the negative aspects of narcissism and promote its benefits has important implications for both scholars and practitioners. This study proposes two managerial practices (i.e. promotions based on relative performance and empowering leadership) that motivate employees with high narcissism to bring benefits to the workplace. Drawing on expectancy theory, we theorize that narcissism, promotions based on relative performance, and empowering leadership each influence valence, instrumentality, and expectancy, respectively, thereby driving diverse information searching, which indirectly increases radical and incremental creativity. The results of a multi-time and multi-source field study of 462 employees on 88 teams indicate that narcissism is positively associated with diverse information searching when team leaders evaluate promotions based on relative performance and empower narcissistic employees. Moreover, there is an indirect relationship between a three-way interaction (i.e. narcissism × promotions based on relative performance × empowering leadership) and radical and incremental creativity via diverse information searching. We conclude by discussing the theoretical and practical implications of these findings, offering insights into more effective management of employees with high narcissism at work.
Development and characterization of a through-air thermobonding process with high heating rate for activating the binder and producing preforms for fibre-reinforced polymers
Authors: Hellmann Sven , Gereke Thomas , Truemper Wolfgang , Cherif Chokri
Published: March 2024

This study focuses on the development of an advanced high heating rate thermobonding process for the manufacture of preforms and the metrological characterisation of the process. The process involves passing hot air, driven by pressure differential, through a textile stack consisting of several plies of a quadraxial fabric coated with a binder. Heat is transferred into the stack and into the binder by forced convection, melting the binder. The process is used in the same way to cool the stack and binder so that the plies are bonded together. The pressure differential compacts the stack. The comprehensive methodological characterisation of the process includes first determining the air permeability of the stack and thus the volume flow of air as a function of the number of plies stacked. Further characterisation focuses on a comprehensive determination of the heating behaviour in the individual plies as a function of time, using thermocouples and thermal imaging to determine the temperatures of hot air and textiles. These are compared and related using a mathematical approach as different values have been found. The results indicate high heating rates, reducing process time by at least 85% compared to previous binder activation methods. In addition, the cantilever method assesses the flexural stiffness of the processed stacks and shows a twofold improvement in bond strength compared to uncompacted stacks. Results and discussions include orifice based volume flow determination, thermography calibration, mathematical modelling, stiffness of bonded textile plies, process comparison, process control and potential energy savings.
Work Preferences, Control, and Independence among Midlife and Older Adults in Aotearoa/New Zealand
Authors: Newton Nicky J. , Davey Judith , Alpass Fiona
Published: March 2024

In 2023, current life expectancy for adults aged 65 and over in Aotearoa/New Zealand ranged from 84.6 to 89.2 years. Mandatory retirement has been abolished, but pension age eligibility remains at age 65. However, some older adults prefer to continue working, often experiencing a mismatch between current and preferred work statuses. The current study used data drawn from the 2020 wave of the New Zealand Health, Work and Retirement study (HWR; N  =  3,916; Mage  =  66.84) to examine associations between work preferences and perceptions of control and independence. We found that those not working but who preferred to work reported the lowest levels of perceived control and independence. Conversely, work preference match and higher levels of perceived control and independence were positively related to life satisfaction. The current study adds to our understanding of the centrality of work status, perceived control, and perceived independence among midlife and older adults, particularly in Aotearoa/New Zealand.
Continuity in Socialization Styles: Typologies of Socialization in the Different Life Stages of Older People
Authors: Porras-Mendoza Yoselyn , Celdrán Montserrat , Zacarés Juan José
Published: March 2024

The purpose of this research was to identify the socialization styles of the older person (such as authoritative, indulgent, authoritarian, and negligent) in three different roles: (1) nowadays as a grandparent, (2) considering the style used to educate their own children in the past; and (3), considering the socialization style they received when they were children. The sample (317 people over 65 years old with at least one grandchild aged up to 16 years old participated) received the questionnaire on socialization styles in those roles. The results showed the predominance of the indulgent style in their role as grandparents. Almost 80% showed intergenerational continuity between at least two roles, with the exception of those with a neglectful style. Continuity in socialization style is crucial to understanding the dynamics within family relationships, which have highly durable intergenerational ties.
Clinical presentation and management outcome of pediatric intussusception at Wolaita Sodo University Comprehensive Specialized Hospital: a retrospective cross-sectional study
Authors: Zewde Yohannes , Bugie Tamrat , Daniel Abel , Wodajo Awoke , Meskele Mengistu
Published: March 2024

Objective

To assess the pattern of clinical presentations and factors associated with the management outcome of pediatric intussusception among children treated at Wolaita Sodo University Comprehensive Specialized Hospital, Ethiopia.

Methods

This retrospective cross-sectional study included the medical records of 103 children treated for intussusception from 2018 to 2020. The data collected were analyzed using SPSS 25.0 (IBM Corp., Armonk, NY, USA).

Results

In total, 84 (81.6%) patients were released with a favorable outcome. Ileocolic intussusception was a positive predictor, with a nine-fold higher likelihood of a favorable outcome than other types of intussusception [adjusted odds ratio (AOR), 9.16; 95% confidence interval (CI), 2.39–21.2]. Additionally, a favorable outcome was three times more likely in patients who did than did not undergo manual reduction (AOR, 3.08; 95% CI, 3.05–5.48). Patients aged <1 year were 96% less likely to have a positive outcome than those aged >4 years (AOR, 0.04; 95% CI, 0.03–0.57).

Conclusion

Most patients were discharged with favorable outcomes. Having ileocolic intussusception and undergoing manual reduction were associated with significantly more favorable outcomes of pediatric intussusception. Therefore, nonsurgical management such as hydrostatic enema and pneumatic reduction is recommended to reduce hospital discharge of patients with unfavorable outcomes.
The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer
Authors: Li Xiu-Feng , Zhang Xiu-Juan , Hao Fu-Rong , Dong Xiao-Tong , Xu Guo-Dong , Zhang Yun-Xiang
Published: March 2024

Objective

To investigate the roles and underlying mechanisms of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer (GC).

Methods

VEGFR-3 gene expression profiles in human gastric adenocarcinoma (GAC) tissues were analysed using The Cancer Genome Atlas database. Human GC cell lines and were used for in vitro studies. Mouse models of GC and distant metastasis were used for in vivo studies. Silencing of VEGFR-3 gene expression was achieved using small interfering RNA.

Results

VEGFR-3 gene expression was significantly elevated in GAC tissues and GC cells. Higher VEGFR-3 expression was positively correlated with more advanced stages and a greater number of metastatic lymph nodes. In vitro studies in GC cells showed that knockdown of VEGFR-3 gene expression significantly suppressed cell proliferation and migration, but promoted apoptosis. In vivo investigations revealed that silencing of VEGFR-3 gene expression exhibited significant inhibition on tumour growth and metastasis. Further mechanistic studies showed that VEGFR-3 exerted its pathological roles by affecting the key molecules in the apoptotic and epithelial–mesenchymal transition pathways.

Conclusion

The molecular pathways associated with VEGFR-3-mediated pathological effects could be targets in the development of novel approaches for the diagnosis, prognosis and treatment of GC.
Melatonin in hemicrania continua and paroxysmal hemicrania
Authors: Cheung Sing-ngai , Oliveira Renato , Goadsby Peter J
Published: March 2024

Background

Hemicrania continua (HC) and paroxysmal hemicrania (PH) belong to a group of primary headache disorders called trigeminal autonomic cephalalgias. One of the diagnostic criteria for both HC and PH is the absolute response to the therapeutic dose of indomethacin. However, indomethacin is discontinued in many patients as a result of intolerance to its side effects. Melatonin, a pineal hormone, which shares similar chemical structure to indomethacin, has been reported to have some efficacy for HC in previous case reports and series. To our knowledge, there is no literature regarding the use of melatonin in PH. We aimed to describe the clinical use of melatonin in the preventive management of HC and PH.

Methods

Patient level data were extracted as an audit from routinely collected clinical records in consecutive patients seen in outpatient neurology clinic at King’s College Hospital, London, UK, from September 2014 to April 2023. Our cohort of patients were identified through a search using the keywords: hemicrania continua, paroxysmal hemicrania, melatonin and indomethacin. Descriptive statistics including absolute and relative frequencies, mean ± SD, median and interquartile range (IQR) were used.

Results

Fifty-six HC patients were included with a mean ± SD age of 52 ± 16 years; 43 of 56 (77%) patients were female. Melatonin was taken by 23 (41%) patients. Of these 23 patients, 19 (83%) stopped indomethacin because of different side effects. The doses of melatonin used ranged from 0.5 mg to 21 mg, with a median dose of 10 mg (IQR = 6–13 mg). Fourteen (61%) patients reported positive relief for headache, whereas the remaining nine (39%) patients reported no headache preventive effect. None of the patients reported that they were completely pain free. Two patients continued indomethacin and melatonin concurrently for better symptom relief. Eight patients continued melatonin as the single preventive treatment. Side effects from melatonin were rare. Twenty-two PH patients were included with mean ± SD age of 50 ± 17 years; 17 of 22 (77%) patients were female. Melatonin was given to six (27%) patients. The median dose of melatonin used was 8 mg (IQR = 6–10 mg). Three (50%) patients responded to melatonin treatment. One of them used melatonin as adjunctive treatment with indomethacin.

Conclusions

Melatonin showed some efficacy in the treatment of HC and PH with a well-tolerated side effect profile. It does not have the same absolute responsiveness as indomethacin, at the doses used, although it does offer a well-tolerated option that can have significant ameliorating effects in a substantial cohort of patients.
Closed reduction of dislocated hip prosthesis using a traction table
Authors: Shigemura Tomonori , Yamamoto Yohei , Murata Yasuaki
Published: March 2024

This article describes three cases in which a dislocated hip prosthesis was reduced by a new reduction technique – that we previously described – using traction table. The dissociation of a prosthesis is a rare but serious complication of closed reduction manoeuvre. The new reduction manoeuvre using a traction table may be a good option to avoid dissociation of the prosthesis during closed reduction for treatment of dislocation after total hip arthroplasty.
Economic Empowerment for Enhanced Health Equity: A Qualitative Study of Women Living with HIV in Wakiso District, Uganda
Authors: Najjuma Saidah Mbooge , Yates Helen T.
Published: March 2024

Women living with HIV in Sub-Saharan Africa struggle for health equity while also facing the constraints of economic hardship and patriarchy. In this article, we describe the experiences of women who participated in economic empowerment groups for women living with HIV in Wakiso district, Uganda. Fifty women engaged in economic empowerment groups and ten social worker and community health worker key informants enrolled in the study. Taking a phenomenological approach, we used field notes, qualitative interviews, and focus groups with participants and key informants to describe the experiences of the women who joined the groups. We present the findings including enhanced management of HIV and increased property and business ownership due to economic empowerment group participation. We discuss the findings through an economic empowerment framework and offer implications for social work interventions and research.
Effect of COVID-19 Pandemic on Physical Activity and Screen Time of School Children: A Cross-sectional Study from Chandigarh
Authors: Narang Kavita , Thakur Jarnail Singh , Das Karobi , Garg Aarti , Narang Tarun
Published: March 2024

Background

The nationwide lockdown imposed due to the COVID-19 pandemic disrupted daily routines, especially for children. Being at home and attending virtual classes unintentionally precipitated an increase in both academic and nonacademic screen time and probably led to decreased physical activity in children. However, there is lack of evidence related to the physical activity and screen time of school-age children during the COVID-19 pandemic. So this study aimed to investigate the effect of the COVID-19 pandemic and lockdown on physical activity and screen time of children.

Methods

An online survey was used to recruit parents of school-age children through convenience sampling. Parents were asked to compare their child’s physical activity and screen time in the previous week with those in the pre-lockdown and lockdown periods. The global physical activity questionnaire was used to assess physical activity, and a screen time questionnaire was developed and validated. Data collection was done from September 2020 to December 2020.

Results

Data of 104 children were collected from parents’ reports. The average age of parents was 39.1 + 4.8 years for mothers and 40.8 + 6.9 years for fathers. Results revealed a decrease in physical activity from 564.95 min/week before the lockdown to 146.05 min/week during the lockdown, with the absolute decrease of 448.9 min/week. Total screen time increased from 2.42 h/day before the lockdown to 7.41 h/day during the lockdown.

Conclusion

Necessary steps to mitigate the effect of COVID-19 pandemic unintentionally affected children in terms of decreased physical activity and increased screen time.
Efficacy of Educational Intervention on Decision Conflict
Authors: Kaur Ramandeep , Madaan Dimple , Pandher Dilpreet
Published: March 2024

Background

Decision conflict usually occurs from poor patient involvement in decision making which may cause regrets about the options that were chosen. Health professionals should impart antenatal education to enhance a mother’s belief about her birthing.

Objective

To assess the effect of supportive educational intervention on decision conflict among primipara mothers with a fear of childbirth (FOC).

Methods

An randomized controlled trial (RCT) was conducted on 205 primipara mothers with an FOC attending Gynae OPD. At 24–28 weeks of pregnancy, mothers were screened for FOC WDEQ-A and then randomly allocated to the experimental (103) and control group (102) and assessed for decision conflict by using a decisional conflict scale. The experimental group was given Supportive educational intervention. At 37–38 weeks of pregnancy, both groups were again assessed for decision conflict. Three participants from the experimental and two from the control group were lost to follow up and the final post-test was completed by 200 participants. Data analysis was done by calculating frequency, mean, standard deviation, Fisher Exact test, chi-square, t-test and F-test using SPSS version 18.

Results

There was a significantly lower post-intervention decision conflict score in the experimental group as compared to the control group ( p < .001). No difference was observed in the pre-test score in both groups.

Conclusion

Supportive educational intervention was effective in primipara mothers for reducing decision conflict. Improving antenatal emotional well-being will lead to a positive childbirth experience with better perinatal outcomes.
Elastic Chain Premaxillary Retraction Appliance Does Not Increase Inter-Canthal Dimension in Patients with Bilateral Cleft Lip and Palate
Authors: Burashed Hamad , Resnick Cory M. , Ross Elizabeth E. , Mulliken John B. , Padwa Bonnie L.
Published: March 2024

Objective

To determine if the elastic chain premaxillary retraction (ECPR) appliance increases inter-medial and inter-lateral canthal dimension in patients with bilateral complete cleft lip and palate (BCLP).

Design

Retrospective cohort study.

Setting

Specialized tertiary care facility.

Patients, Participants

126 patients with BCLP; 75 had ECPR, 51 had no pre-surgical manipulation.

Interventions

Three-dimensional facial photographs were obtained prior to insertion of appliance (T0), post-appliance therapy prior to appliance removal/labial repair (T1), and several months after labial repair (T2) for a longitudinal ECPR group, and were obtained after age 4 years (T3) for a non-longitudinal ECPR group and for the non-ECPR group.

Main Outcome Measures

Inter-medial and inter-lateral canthal dimension (en-en, ex-ex) was determined for all groups/time-points. Measurements were compared between groups and to norms.

Results

The mean en-en and ex-ex was 32.6 ± 3.2 mm and 84.4 ± 6.3 mm for the ECPR group and 33.5 ± 3.1 mm and 86.7 ± 7.2 mm for the non-ECPR group at T3. Inter-medial and inter-lateral canthal dimensions were significantly greater than normal ( P < .05) in both groups; there was no significant difference between groups ( P > .05). The mean en-en and ex-ex for the Longitudinal ECPR group was 27.5 ± 2.4 mm and 66.7 ± 3.7 mm at T0, 29.6 ± 2.4 mm and 70.4 ± 2.9 mm at T1, and 29.2 ± 2.3 mm and 72.3 ± 3.8 mm at T2. en-en and ex-ex increased significantly from T0-T1 ( P < .05), decreased at T2 ( P > .05) and was significantly larger than normal at all time-points ( P < .05).

Conclusions

Inter-medial and inter-lateral canthal dimension increased after ECPR but returned to baseline growth trajectory. These dimensions were above normal at all time-points. There was no difference between those that did and did not have dentofacial orthopedic manipulation.
Application of Multi-Attribute Utility Analysis as a Methodological Framework in Academic–Clinical Partnership Evaluation
Authors: North Sara E.
Published: March 2024

A method called multi-attribute utility analysis (MAUA) provides a decision-making framework that facilitates comparative analysis of multiple real-world decision alternatives with unique complex attributes. Utility analysis as a measure of effectiveness has been minimally used by educational researchers to date, despite clear relevance in complex decision-making. To illustrate its viability, the application of MAUA was modeled for two example academic programs with diverse partnership priorities as a form of assessing academic–clinical partnership alignment. Simulated application indicates MAUA may be successfully utilized as an evidence-based methodological framework. The presented example is illustrative of the wide-spanning potential for this approach in different contexts, as predicted and recommended by experts in the field. Evaluators are encouraged to collaborate in new ways and strive to produce tangible, solution-oriented approaches to address key challenges and demonstrate the value of sound evaluation practices.
A collaborative autoethnographic journey of collective storying: Transitioning between the ‘I’, the ‘We’ and the ‘They’
Authors: Dyer Suzette , Hurd Fiona , Kenworthy Amy , Hedges Peggy , Wall Tony , Sankaran Shankar , Jones David Raymond
Published: March 2024

The story we share here is about lessons learned during a three-year, collaborative autoethnographic journey beginning in January 2020. Our story is one of conducting a meaningful inquiry into our shared lived experience amid the changes brought about by COVID-19 lockdowns. Our insights speak to how we collaboratively reflected and researched across institutions, countries, disciplines, and career stages. More importantly, in making our process explicit, we highlight the way storying was experienced within our collective space. In doing so, we explore insights about how stories are adapted and transformed through a process of navigating the development of, and transitions between, pre-public and public spaces. Using an Arendtian lens, we explore the question, How are autoethnographic collaborative stories crafted for research in an academic context? Our insights present a cyclical and developmental frame within which to process collaborative storying and indeed collaborative academic work.