bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Problematic Physical Activity (PPA) a Uni- or Multi-Dimensional Concept? A Bifactor Analysis of the Exercise Dependence Scale-Revised (EDS-R)
Authors: Kern Laurence , Mattar Lama , Kotbagi Gayatri , Romo Lucia , Morvan Yannick
Published: December 2023

The study of exercise dependence, or as we prefer, problematic physical activity (PPA), faces both theoretical and methodological challenges. Different factorial solutions were obtained for the widely used Exercise Dependence Scale-Revised (EDS-R), leading us to question both its latent underlying construct and the interpretation of its factor solutions. Through confirmatory factor analysis (CFA) and the use of a bifactor model (BCFA), we assessed the dimensionality of a French version of the EDS-R. We recruited 745 students from Paris Nanterre University, but we removed 88 responses (16.8%) to retain only those who (a) engaged in a moderate to high levels of physical activity, according to the Global Physical Activity Questionnaire (GPAQ; N = 494; 9.5%), and (b) completed the EDS-R. We used a final sample of 435 students (58.4% of the total population) for a factorial analysis of the EDS-R. We conducted a three-step CFA in Mplus, producing three models: (a) unidimensional, (b) second-order, and (c) bi-factor (BCFA). The results of the BCFA indicated that most EDS-R items were better indicators of a general factor than their respective group factors, except for the second factor measuring a withdrawal construct. These results add to an ongoing debate in the field of behavioral addiction as to how to better conceptualize and measure exercise dependence or PPA. Withdrawal appears to have a special position in this debate, since our BCFA suggested that it is the only specific sub-dimension of the EDS-R scale.
An Unstable Presence in the House: Rethinking the Threat of Disability in 2 Sam 5:6–8 and the Mephibosheth Story
Authors: Jones Kirsty
Published: December 2023

In this article, I survey exegetical approaches to the “blind and lame,” using disability studies and close readings to expose ableist bias. I also present my reading, in which I propose that the blind and lame are disabled persons whom David hates not just because of who they are, but also because of the fears they provoke. He is afraid. Disabled bodies can be unpredictable, untamable, and uncertain. David has no idea what his enemies are capable of, because “blind” and “lame” are vague and amorphous labels. Parading blind people and lame people on the ramparts does not display the weakest people in a strong city but displays people of unknown strengths.
Social Change, Employment and Development in Weekly Rural Markets in Odisha
Authors: Tiwari Manish , Sahu Rama Shankar
Published: December 2023

Local rural markets ( haats) are considered important spaces of economic and social exchange all over South Asia. Based on a detailed ethnography in four weekly haats in Koraput district of Odisha in India, this article confirms their functions as dynamic socio-cultural gendered public spaces as well as crucial hubs of economic activities for rural areas. However, going beyond local ethnography, and seeking to understand how these weekly markets socially and economically empower poor rural tribals as well as non-tribals, this article problematises the role of middlemen. They not only regulate these markets but also control the terms of trade and profits while connecting local markets to higher scales of South Asia’s food security chains. Our concluding analysis identifies some key risks and opportunities faced by producers, sellers and buyers as participants in these weekly markets, which are now clearly glocalised spaces.
Mandatory Vision Test for Driver License Renewal in Association With Traffic Fatality and Injury Among Older Road Users in Utah
Authors: Pan Yuhan , Evans Alexander , Benedetti Marco H. , Zhu Motao
Published: December 2023

In 2011, Utah began requiring that drivers aged 65 years and older pass a vision test at each license renewal. This study aims to investigate if the mandatory vision test associated with motor vehicle fatality and injury rates in older road users. We fit controlled interrupted time series analysis models to compare fatality and injury rates for older adults (65+) affected by the law to younger adults (45–64) unaffected by the law. The models yielded estimates of differential level and slope changes in fatality and injury rates, which we used to estimate policy associations. We did not find evidence that implementing an accelerated vision test for older adults in Utah was associated with a reduction in injury or fatality rates among older (65+) drivers and non-drivers relative to those aged 45–64. Other strategies might be considered to prevent fatal motor vehicle crashes (MVCs) in older adults.
Promoting Equity, Diversity, and Inclusion in Medicine: A Comprehensive Toolkit for Change in Radiology
Authors: Sharma Sonali , Hillier Tracey , Parsons Marlee , Glanc Phyllis , Miller Elka , Nguyen Elsie T. , Doria Andrea S. , Dhillon Sukhvinder , Seely Jean M. , Borgaonkar Joy , Yong-Hing Charlotte J.
Published: December 2023

This toolkit presents a comprehensive framework for a toolkit intended to increase equity, diversity, and inclusion (EDI) within the medical field and recommendations. We advocate for clear, comprehensive definitions and interpretations of fundamental EDI terms, laying the groundwork necessary for initiating and maintaining EDI initiatives. Furthermore, we offer a systematic approach to establishing EDI committees within medical departments, accentuating the pivotal role these committees play as they drive and steer EDI strategies. This toolkit also explores strategies tailored for the recruitment of a diverse workforce. This includes integral aspects such as developing inclusive job advertisements, implementing balanced search methods for candidates, conducting unbiased appraisals of applications, and structuring diverse hiring committees. The emphasis on these strategies not only augments the diversity within medical institutions but also sets the stage for a more holistic approach to healthcare delivery. Therefore, by adopting the recommended strategies and guidelines outlined in this framework, medical institutions and specifically radiology departments can foster an environment that embodies inclusivity and equity, thereby enhancing the quality of patient care and overall health outcomes.
Re-imagining and repositioning the lived experience of children seen as outsiders in Kenya
Authors: Ngutuku Elizabeth
Published: December 2023

This paper explores the contested identity and belonging for outsider-children in Kenya. I explore the experience of children born out of marriage, those from other unions, the emergent insider-outsider child and children labouring to belong. Locating this experience in a relatively protective customary and legal regime, the context of poverty and the local imaginaries of belonging reveals the complexities that animate children’s lives. I argue that children’s best interests as embedded in law, should enter into conversation with children’s lived realities.
An innovative nano-porous copper composite without using a pore-forming agent
Authors: Yehia Hossam M , Elkady Omayma A , El-Geassy Abdel-Hady A , Abd-elmotaleb Tamer , Bahlol Mohamed , Kamal Abdullah
Published: December 2023

In this research, a new nano-open porous copper without using a pore-forming agent was innovated. Five copper samples which are pure copper, Cu/2.5%Al2O3, Cu/2.5(Al2O3-GNs)Ag, Cu/5(Al2O3-GNs)2.5Ag, and Cu/7.5(Al2O3-GNs)2.5Ag were prepared using the electroless coating process. The samples were characterized by studying their chemical composition, microstructure, total pore area, bulk density, apparent density, and porosity percent. Also, the hardness and corrosion rate were studied. The SEM emphasized the formation of open pores with homogeneous distribution. Agglomeration of the new hybrid (Al2O3/GNs) was observed at 7.5%. The porosity percent and total pore area were increased gradually by adding 2.5%Al2O3 and different ratios of the new hybrid. The 7.5% (Al2O3-GNs) sample recorded the highest porosity percentage 32.86%. The sample 7.5% (Al2O3-GNs) exhibits the highest incremental pore volume in the micro-pore regions. The 5% (Al2O3-GNs) sample recorded the highest cumulative pore volume in the nanopore diameter region. The hybrid reinforcement (Al2O3/GNs) achieved hardness better than the single reinforcement (Al2O3). The hardness decreased gradually due to increasing the porosity percent and forming some agglomerations of the (Al2O3/GNs)Ag at 7.5%. The Cu/2.5(Al2O3/GNs)Ag sample recorded the lowest corrosion rate of 3.31 mm/year.
Ballistic characterization of additively manufactured extrusion deposited thermoplastic composite plates
Authors: Landrie Dakota M , Tekinalp Halil , Hassen Ahmed , Theodore Merlin , Vaidya Uday
Published: December 2023

Additive manufacturing (AM) is rapidly emerging in high performance applications such as army ground vehicles, automotive and transportation. However, the response of AM parts/components to extreme loading such as high velocity impacts is less studied. In this work, the performance under ballistic impact of AM panels is evaluated using a medium velocity gas gun, generating projectile velocities up to 400 m/s. The preferential print orientation properties are considered in order to evaluate whether the panels exhibit isotropic or anisotropic behavior under impact. Surface morphology is investigated by milling the beads smooth on samples and comparing the impact on as-printed samples to those that are smoothed. The effect of nickel chromium micron (nichrome) wire embedded in the AM panels (during print) of polycarbonate-carbon fiber (PC-CF) and polycarbonate-glass fiber (PC-GF) are explored. Thermoplastic polyurethane-acrylonitrile butadiene styrene/carbon fiber (TPU-ABS/CF), Acrylonitrile butadiene styrene-carbon-fiber (ABS-CF) AM samples absorbed >50% of the impact energy. The ballistic performance was noted to be in the following order – ABS-CF > TPU-ABS/CF > PC. Scanning electron microscopy (SEM) was conducted to study the interface between the nichrome wire and the polymer-fiber matrix. This work is the first of its kind exploring into the capabilities of AM panels as ballistic materials. This study leads the way for developing AM panels that are easily manufactured and exhibit superior ballistic resistance.
Foreign Aid, Political Power and FDI: Do Aid-dependent Institutions Facilitate Investment in Africa?
Authors: Wang Dongni , Fillat-Castejón Carmen
Published: December 2023

In this article, we examine the nexus between foreign development assistance and the attraction of foreign direct investment (FDI) through a de facto political power, as an aid-seeking and likely aid-dependent group. We apply structural equation modelling to investigate the direct and indirect effect of aid on FDI via economic institutions for a sample of 42 African countries from 2002 to 2016. Our results corroborate a direct positive effect of aid and institutions on FDI as a productive financial source. However, an aid-dependent de facto political power does not improve the economic institutions, and within a broad institutional context, it may even worsen them, evidencing the indirect effect of reducing a country’s attractiveness for FDI. This study offers robust evidence under different specifications and variables of institutions in addition to several controls for political and strategic interests and economic conditions. We ultimately develop a model explaining why aid barely makes any contribution to institutional reforms. In countries that are heavily dependent on aid, the beneficiary group is discouraged from improving institutional qualities as the source of benefits would be discontinued.
Artificial Intelligence Augmented Qualitative Analysis: The Way of the Future?
Authors: Hitch Danielle
Published: December 2023

The artificial intelligence (AI) revolution is here and gathering momentum, thanks to new models of natural language processing (NLP) and rapidly increasing adoption by the public. NLP technology uses statistical analysis of language structures to analyse and generate human language, using text or speech as its source material. It can also be applied to visual mediums like images and videos. A few qualitative research early adopters are beginning to adopt this technology into their work, but our understanding of its potential remains in its infancy. This article will define and describe NLP-based AI and discuss its benefits and limitations for reflexive thematic analysis in health research. While there are many platforms available, ChatGPT is the most well-known and accessible. A worked example using ChatGPT to augment reflexive thematic analysis is provided to illustrate potential application in practice. This article is intended to inspire further conversation around the role of AI in qualitative research and offer practical guidance for researchers seeking to adopt this technology.
Reading ability and challenges in a project-based academic report writing course: A test of the threshold hypothesis
Authors: Wang Chunyan , You Xiaoqiong , Lu Jiawei
Published: December 2023

Interest in the use of project-based academic report writing (PBARW) has continued unabated for the past 10 years in Asian countries, especially in China. However, cognitive challenges faced by second language (L2) learners – most notably the challenge of reading authentic academic literature – are often reported by practitioners. This article explores the relationship between Chinese college students’ English reading comprehension ability and the challenges they encountered in a project-based academic report writing course. A total of 274 students in Shanghai were surveyed on the challenges they met when implementing PBARW tasks. Their English reading abilities were also collected. With ANOVA and piecewise regression analyses, the study revealed a clearly discernible reading comprehension ability threshold: below the threshold, English reading ability had a direct counteractive effect on the challenges of studying a PBARW course; the higher the reading ability, the lower the challenges perceived. Beyond that threshold, English reading ability stopped mitigating challenges directly. English reading abilities divided by the threshold moderated the effects of writing topic knowledge and writing strategies on student difficulties: only the good readers were able to overcome challenges they encountered effectively by drawing on the topic knowledge possessed and writing strategies adopted. In the future, researchers may observe the reading abilities required in different disciplines and PBARW tasks. Pedagogical implications for the findings of the research are discussed.
Results-based agri-environmental scheme design: Legal implications
Authors: Cardwell Michael
Published: December 2023

Results-based agri-environmental schemes look set over the years ahead to form core components of agricultural policy both within the European Union and the United Kingdom. Their level of ambition, however, raises specific legal issues, four of which will be explored: first, the governance dimension when ‘setting the bar’ for the unlocking of payment; secondly, potential regulatory and contractual responses where there is a failure to meet the mandated outcome; thirdly, challenges for tenants who enjoy insufficient security of tenure to achieve long-term objectives and/or who are subject to clauses in their agreements or statutory provisions which have the effect of restricting the use of the land to ‘agriculture’ as traditionally understood; and, fourthly, compatibility with World Trade Organization rules. While results-based agri-environmental schemes may be more complex to translate into practice than those based upon prescribed actions, there is scope for the law in both its regulatory and contractual forms to be enlisted as a powerful ally in their realisation.
Assessments of tumor mutational burden estimation by targeted panel sequencing: A comprehensive simulation analysis
Authors: Li Dan , Wang Dong , Johann Donald J , Hong Huixiao , Xu Joshua
Published: December 2023

Tumor mutational burden (TMB), when at a high level, is an emerging indicative factor of sensitivity to immune checkpoint inhibitors. Previous studies have shown that the more affordable and accurate targeted panels can be used to measure TMB as a substitute for whole exome sequencing (WES). However, additional processes, such as hotspot mutations exclusion and TMB adjustment, are usually required to deal with the effect of the limited panel sizes. A comprehensive investigation of the effective factors is needed for accurate TMB estimation by targeted panels. In this study, we quantitatively evaluated the variances of TMB values calculated by WES and targeted panels using 10,000 simulated targeted panels with panel sizes ranging from 0.2 to 3.1 million bases. With The Cancer Genome Atlas (TCGA) cancer samples and mutation profiles, we fixed regressions on WES-TMBs and panel-TMBs to assess the performance of a given targeted panel. Panel size was found as one of the major effective factors of TMB estimation. Meanwhile, by investigating the well-performing small panels that reported TMB values similar to those of WES, we demonstrated the evidence of the cancer type–specific impacts of genes on TMB estimation and identified high-impact gene sets for different cancer types based on the TCGA data. This study revealed the quantitative correlations between TMB variance and panel size, and the potential impacts of individual genes on TMB estimation. Our results suggested that for cancer patients diagnosed using targeted panels, it would be highly beneficial to have the capability to directly measure TMB from the targeted sequencing data. This would greatly assist in making decisions regarding the use of immunotherapies.
Les pratiques de l’action intersectorielle locale pour l’équité en santé : étude du cas Quartier nourricier de la Corporation de développement communautaire Centre-Sud à Montréal
Authors: Bertrand Laurence , Chabot Catherine , Di Sante Mélissa , Bilodeau Angèle , Potvin Louise
Published: December 2023

Introduction :

Afin d’agir sur les inégalités de santé et les ressources locales promotrices de santé, les praticiens et les décideurs doivent être outillés pour pratiquer l’action intersectorielle locale. Planifier et optimiser ces partenariats demeure pourtant un défi en raison du manque de connaissances sur les processus menant à l’atteinte de leurs objectifs – ce qu’ils font et comment. Cette étude documente empiriquement, à l’aide d’une étude de cas, les pratiques de conception de l’action intersectorielle locale dans la démarche Quartier nourricier (QN) à Montréal.

Méthodes :

Une analyse secondaire d’un sous-ensemble des données originales du programme de recherche Valeur de l’action intersectorielle locale a été effectuée. Les données qualitatives sont issues d’une collecte de données prospective ayant suivi l’évolution du système d’action complexe QN entre mars et novembre 2014. Les traces observables de l’action ont été relevées dans des notes d’observation, des documents et des entretiens téléphoniques, puis codifiées dans une matrice chronologique d’évènements critiques et une matrice ordonnée par rôle. L’analyse inductive des matrices a identifié les éléments significatifs pour expliquer le déroulement de l’action.

Résultats :

Trois opérations interdépendantes et concomitantes affectent à la fois la relation entre les partenaires et la conception du projet : (a) l’idéation sous contraintes, (b) la négociation de priorités, et (c) la représentation politique. Chaque opération présente un ensemble de pratiques qui font progresser l’action intersectorielle locale.

Conclusion :

Mettre en lumière les pratiques du terrain, en les ancrant dans trois opérations nécessaires pour effectuer des transformations dans les environnements locaux favorables à la santé, permet de guider la planification des stratégies et la conduite des actions pour mener des partenariats intersectoriels.

Mots clés :

Action communautaire, action intersectorielle locale, collaboration/partenariats, conception, développement des capacités (y compris les compétences), environnements favorables à la santé, étude de cas, promotion de la santé, réalisme critique, urbanisme/santé urbaine/milieu urbain
The Goal Is For You to Get Better: Comparing the Representations of Biomedical and Mental Health Treatment in the Television Series Bates Motel
Authors: Hoffman William
Published: December 2023

The current study explored the representation of biomedical treatment and mental health treatment in the television series Bates Motel. We used a sample of episodes from the fourth season of the series to create a set of codes inductively. We did this to answer two research questions about the topics of conversation and verbal expressions with character dialogue. Results revealed the distinctions in topics of conversation and verbal expressions by examining dialogue between either the biomedical patient and mental health patient and a conversation partner. Appendix A shows a detailed listing of episodes coded. Results also showed that communication was more hopeful and agreeable in the biomedical settings, more procedural (or direct), worried, and urgent in the mental health setting. In both settings, we found communication was caring between provider and patient. Future research should expand on this small yet important sample, even considering smaller samples of episodes as case studies of media representations of health settings.
Appendicitis: A Hidden Danger of GLP-1 Receptor Agonists?
Authors: Casella Sarah , Galli Katelyn
Published: December 2023

Introduction: While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become increasingly prescribed, use is often inhibited by the gastrointestinal adverse effects that patients must endure. Nausea, vomiting, and cholelithiasis are most commonly associated with use, with little to no data or labeling reflecting risk of appendicitis or associated symptoms. Appendicitis etiology is theorized to develop secondary to obstruction of the vermiform via infection or fecalith causing an increase in intraluminal pressure. It is hypothesized that given the aforementioned gastrointestinal effects associated with GLP-1 RAs, patients taking such agents may be more at risk for developing this acute condition. Patient Case: We describe a case of a 48-year-old woman who presented to the emergency department several months after being initiated on Ozempic (semaglutide). This report aims to analyze the potential secondary adverse effects that may result from GLP-1 RA use. Her examination was positive for focal abdominal tenderness and leukocytosis along with imaging suggestive of appendicitis. Her acute condition ultimately required an appendectomy. Discussion: While minimal data are available to suggest significant causation between GLP-1 RAs and appendicitis, a literature and database search revealed that instances may be more common than previously thought. Conclusion: Trial results and adverse event reporting systems report an infrequent incidence in patients using these medications, but this report aims to contribute to the literature describing this potential adverse event.
Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL
Authors: Epperly Rebecca , Shah Nirali N.
Published: December 2023

The tremendous successes of CD19-directed CAR T cells in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) has led to the more widespread use of this important treatment modality. With an ability to induce remission and potentially lead to long-term survival in patients with multiply relapsed/chemotherapy refractory disease, more children are now receiving this therapy with the hope of inducing a long-term durable remission (with or without consolidative hematopoietic cell transplantation). While overcoming the acute toxicities was critical to its broad implementation, the emerging utilization requires close evaluation of subacute and delayed toxicities alongside a consideration of late effects and issues related to survivorship following CAR T cells. In this underexplored area of toxicity monitoring, this article reviews the current state of the art in relationship to delayed toxicities while highlighting areas of future research in the study of late effects in children and young adults receiving CAR T cells.
Chronic GVHD: review advances in prevention, novel endpoints, and targeted strategies
Authors: Amanam Idoroenyi , Otoukesh Salman , Al Malki Monzr M. , Salhotra Amandeep
Published: December 2023

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for many malignant and non-malignant hematologic disorders. Chronic graft-versus-host (cGVHD) disease remains a significant hurdle for long-term survival in patients post allo-HCT, and it remains the leading cause of late non-relapse mortality. The risk factors for development of cGVHD include degree of human leukocyte antigen (HLA) disparity, increasing recipient age, use of peripheral blood stem cells as a source, myeloablative conditioning regimens, prior acute GVHD (aGVHD), and female donor to male recipient. Our biological understanding of cGVHD is mostly derived from transplantation mouse models and patient data. There are three distinct phases in the development of cGVHD. Approaches to prevent GVHD include pharmacologic strategies such as calcineurin inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil). Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy for GVCHD prevention especially in a setting of reduced intensity conditioning. Other approaches include serotherapy (ATG, Campath) and graft manipulation strategies. A significant obstacle to evaluating the response of novel GVHD-directed therapies has been standardized response assessments. This has functioned as a barrier to designing and interpreting clinical trials that are structured around the treatment of cGVHD. Novel endpoints including failure-free survival, Graft-versus-host disease-free, relapse-free survival (GRFS), and current GVHD-free, relapse-free survival (CGRFS) may create a clearer picture for post-HCT outcomes. Targeted therapies including Bruton's tyrosine kinase inhibition, JAK1/2 inhibition, and ROCK2 inhibitors have improved cGVHD therapy, especially in the steroid refractory setting. Continued improvement in prophylactic strategies for cGVHD, identification of accurate cGVHD treatment endpoints, and access to novel therapeutic agents are expected to improve cGVHD outcomes.
Amyloid consults do not have to be vexing
Authors: D'Souza Anita
Published: December 2023

Diagnosing amyloidosis can be challenging due to its clinical heterogeneity, need for multiple specialists to make a diagnosis, and lack of a single diagnostic test for the disease. Patients are often diagnosed late, in advanced stage, and after exhibiting multiple symptoms and signs for a long period. It is important to develop a clinical suspicion of amyloidosis, particularly in those with multisystemic symptoms and high-risk patient populations such as those with precursor hematologic conditions. A systematic approach to the workup of suspected amyloidosis is key, including a comprehensive clinical assessment, laboratory tests to assess organ involvement, advanced imaging studies, screening for plasma cell disorder, and tissue biopsy when necessary. After making a diagnosis of amyloidosis, accurate typing of amyloid deposits, differentiating between localized and systemic amyloidosis, and appropriately staging the disease is important. Early diagnosis is crucial for improving patient outcomes and quality of life in light chain amyloidosis.
Options at the time of relapse after anti-BCMA therapy
Authors: Razzo Beatrice , Garfall Alfred L. , Cohen Adam D.
Published: December 2023

B-cell maturation antigen (BCMA)–directed therapies, including antibody-drug conjugates, bispecific antibodies (BsAbs), and chimeric antigen receptor T cells (CARTs), have shown remarkable efficacy in patients with late-line myeloma with prior exposure to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. However, optimal sequencing of these agents remains to be determined, and management of these patients once they relapse has become a new unmet need. Fortunately, there are multiple options with demonstrated activity after anti-BCMA therapy, including a different BCMA-directed therapy, non-BCMA-directed CARTs and BsAbs, novel non–T-cell–engaging drugs, and standard triplet/quadruplet regimens or salvage stem cell transplant. Factors to consider when choosing a next therapy after anti-BCMA therapy include patient characteristics and preferences, prior therapies and toxicities, disease biology, timing from last anti-BCMA therapy, and, in the future, BCMA expression and immune profiling. While current data are limited to retrospective studies and small prospective cohorts, the serial use of T-cell–engaging therapies looks particularly promising, especially as BCMA-directed therapies move up earlier in the myeloma treatment course and additional CARTs and BsAbs against alternative targets (eg, G protein–coupled receptor, family C, group 5, member D and Fc receptor-homolog 5) become available. Going forward, ongoing prospective studies, large real-world data sets, and better tools to interrogate antigen expression and immune cell fitness hopefully will provide further insight into how to best individualize therapy for this difficult-to-treat population.
Atypical CML: diagnosis and treatment
Authors: Breccia Massimo
Published: December 2023

Atypical chronic myeloid leukemia (aCML) is included in the group of myelodysplastic/myeloproliferative neoplasms by the International Consensus Classification and has been renamed as MDS/MPN with neutrophilia by the fifth edition of World Health Organization classification. It is always characterized by morphologic identification of granulocytic dysplasia with >10% circulating immature myeloid cells, 2 distinguished features that differentiate this disease among the others. Somatic mutations may help to diagnose but are not specifically pathognomonic of the disease, with the most detected including ASXL1, SETBP1, NRAS, KRAS, SRSF2, and TET2 and with low-frequency CBL, CSF3R, JAK2, and ETNK1. The genomic landscape of aCML has been recently unravelling, revealing that SETBP1 and ETNK1 are usually not ancestral but secondary events associated with disease progression. Unfortunately, until now, no consensus on risk stratification and treatment has been developed: Mayo Clinic prognostic score identified as adverse events age >67 years, hemoglobin level <10  g/dL, and TET2 mutations. Although some possible genetic markers have been identified, allogeneic transplant remains the only curative strategy.
The optimal management of relapsed and refractory Hodgkin lymphoma: post–brentuximab and checkpoint inhibitor failure
Authors: Grover Natalie S. , Dittus Christopher , Thakkar Astha , Beaven Anne W.
Published: December 2023

The treatment landscape of classical Hodgkin lymphoma has changed dramatically over the past decade. Relapsed and refractory mainstay therapeutics such as brentuximab vedotin (BV) and checkpoint inhibitors (CPIs) are being moved to earlier lines of therapy. However, the treatment of patients who progress after BV and CPI remains a challenge. Allogeneic stem cell transplantation still plays an important role in this patient population as the only current treatment approach with curative potential. Unfortunately, not all patients are transplant candidates, and many will still relapse afterward. Cytotoxic chemotherapy and radiation may be used for symptom palliation or as a bridge to transplant. Targeted therapies, including the antibody drug conjugate, camidanlumab tesirine, and transcriptional agents such mammalian target of rapamycin and histone deacetylase inhibitors have shown some potential in patients with refractory disease. In addition, combination therapies with CPIs and novel agents may help overcome resistance to therapy. Clinical trials with cellular therapies, including chimeric antigen receptor T cells targeting CD30 and allogeneic natural killer cells combined with AFM13, a CD30/CD16a-bispecific antibody, have shown promising results. The availability of more therapeutic options for this patient population is eagerly awaited.
Immunotherapy of acquired hemophilia A
Authors: Tiede Andreas
Published: December 2023

Acquired hemophilia A (AHA) is an autoimmune disorder characterized by the formation of autoantibodies that neutralize the function of coagulation factor VIII. Immunosuppressive therapy (IST) with glucocorticoids, cyclophosphamide, rituximab, or combinations thereof is the standard of care to suppress autoantibody formation and induce remission of AHA. About 80% of patients achieve remission over the course of a few weeks to several months. However, patients with AHA are often elderly and frail and have adverse events from IST. Therefore, guidelines suggest an individualized approach using caution in elderly and frail patients. Prophylaxis with emicizumab may reduce the need for early and aggressive IST in the future.
Where have all the platelets gone? HIT, DIC, or something else?
Authors: Jesudas Rohith , Takemoto Clifford M.
Published: December 2023

Thrombocytopenia in ill children is common; accurately diagnosing the underlying etiology is challenging and essential for appropriate management. Triggers for accelerated consumption of platelets are numerous; common downstream mechanisms of clearance include platelet trapping in microvascular thrombi, phagocytosis, and platelet activation. Thrombocytopenia with microangiopathic hemolytic anemia (MAHA) is frequently due to disseminated intravascular coagulation. Thrombotic microangiopathy (TMA) is a subgroup of MAHA. Specific TMA syndromes include thrombotic thrombocytopenic purpura, complement-mediated TMA (CM-TMA), and Shiga toxin–mediated hemolytic uremic syndrome. Isolated thrombocytopenia is characteristic of immune thrombocytopenia; however, concomitant cytopenias are frequent in critically ill patients, making the diagnosis difficult. Immune thrombocytopenia with large vessel thrombosis is a feature of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. In addition, thrombocytopenia is common with macrophage activation, which is characteristic of hemophagocytic lymphohistiocytosis. While thrombocytopenia in ill patients can be driven by hypoproliferative processes such as myelosuppression and/or bone marrow failure, this review will focus on consumptive thrombocytopenia due to immune and nonimmune causes.
Pyruvate kinase activators for treatment of pyruvate kinase deficiency
Authors: Grace Rachael F.
Published: December 2023

Pyruvate kinase (PK) deficiency is a congenital hemolytic anemia with wide-ranging clinical symptoms and complications associated with significant morbidity and reduced health-related quality of life in both children and adults. The management of patients with PK deficiency has been historically challenging due to difficulties in the diagnostic evaluation, heterogeneity of clinical manifestations, and treatment options limited to supportive care with transfusions and splenectomy. An oral allosteric PK activator, mitapivat, is now a clinically available disease-modifying treatment for adults with PK deficiency. Phase 2 and 3 clinical trials of mitapivat have demonstrated sustained improvements in hemolytic anemia, hematopoiesis, and quality of life in many adults with PK deficiency and a generally reassuring safety profile with continued dosing. Additional long-term benefits include rapid and ongoing reduction in iron overload and potential stabilization of bone health. Clinical trials of treatment with mitapivat in children with PK deficiency are ongoing. In addition to disease-modifying treatment with PK activators, gene therapy is a potentially curative treatment currently under evaluation in clinical trials. With the availability of disease-targeted therapies, accurately diagnosing PK deficiency in patients with chronic hemolytic anemia is critical. PK activation and gene therapy have the potential to change the natural history of PK deficiency by improving clinical manifestations and patient quality of life and decreasing the risk of long-term complications.
How to manage splanchnic vein thrombosis in patients with liver disease
Authors: Riva Nicoletta , Ageno Walter
Published: December 2023

Liver cirrhosis and splanchnic vein thrombosis (SVT) are strictly correlated. Portal vein thrombosis, the most common location of SVT, is frequently diagnosed in liver cirrhosis (pooled incidence 4.6 per 100 patient-years), and liver cirrhosis is a common risk factor for SVT (reported in 24%-28% of SVT patients). In cirrhosis-associated SVT, anticoagulant treatment reduces mortality rates, thrombosis extension, and major bleeding, and increases the rates of recanalization, compared to no treatment. Achieving vessel recanalization improves the prognosis of cirrhotic patients by reducing liver-related complications (such as variceal bleeding, ascites, hepatic encephalopathy). Anticoagulation should be therefore routinely prescribed to cirrhotic patients with acute SVT unless contraindicated by active bleeding associated with hemodynamic impairment or by excessively high bleeding risk. Of note, early treatment is associated with higher probability of achieving vessel recanalization. The standard treatment consists of low-molecular-weight heparin, followed by oral anticoagulants (eg, vitamin K antagonists or direct oral anticoagulants), if not contraindicated by severe liver dysfunction. Cirrhotic patients with SVT should be treated long-term (especially if candidate for liver transplantation) since liver cirrhosis is a persistent risk factor for recurrent thrombosis. In this review, we discuss the management of SVT in patients with liver cirrhosis, with a focus on the anticoagulant treatment in terms of indications, timing, drugs, duration, and particular scenarios, such as gastroesophageal varices and thrombocytopenia.
T-cell lymphopenia in frequent volunteer platelet donors
Authors: Kaufman Richard M.
Published: December 2023

In the United States, more than 2 000 000 apheresis platelet units are collected annually from volunteer donors. Platelet donors in the United States and elsewhere are permitted to donate up to 24 times per year. Recently, frequent apheresis platelet donation has been associated with severe T-cell lymphopenia. Several frequent platelet donors have been found to have peripheral blood CD4+ T-cell counts below 200 cells/µL, the threshold for AIDS in HIV-positive individuals. Independent risk factors for plateletpheresis-associated lymphopenia include lifetime donations, age, and donations on the Trima Accel instrument (Terumo BCT), which uses a leukoreduction system (LRS) chamber to trap white blood cells. Less often, severe lymphopenia can occur in donors collected on the Fenwal Amicus instrument (Fresenius Kabi), which has no LRS. For Trima Accel donors, lymphopenia can be partially mitigated by performing a plasma rinseback step at the end of collection. To date, there is no definitive evidence that plateletpheresis-associated lymphopenia is harmful. In a study of frequent platelet donors with lymphopenia who were administered COVID-19 messenger RNA vaccines, immune responses were normal. The homeostatic mechanisms responsible for maintaining a normal peripheral blood T-cell count remain obscure, as do the causal mechanisms underlying plateletpheresis-associated lymphopenia.
Using disease-modifying therapies in sickle cell disease
Authors: Rai Parul , Ataga Kenneth I.
Published: December 2023

As curative therapy using allogeneic hematopoietic stem cell transplantation as well as gene therapy and gene editing remains inaccessible to most patients with sickle cell disease, the availability of drug therapies that are safe, efficacious, and affordable is highly desirable. Increasing progress is being made in developing drug therapies based on our understanding of disease pathophysiology. Four drugs, hydroxyurea, L-glutamine, crizanlizumab, and voxelotor, are currently approved by the US Food and Drug Administration, with multiple others at various stages of testing. With the limited efficacy of individual agents, combinations of agents will likely be required for optimal outcomes.
Gene therapy for sickle cell disease
Authors: Leonard Alexis , Tisdale John F.
Published: December 2023

Sickle cell disease (SCD) is potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after ex vivo genetic modification. Autologous HSCT with gene therapy has the potential to overcome many of the limitations of allogeneic HSCT that include the lack of suitable donors, graft-versus-host disease, the need for immune suppression, and the potential for graft rejection. Significant progress in gene therapy for SCD has been made over the past several decades, now with a growing number of clinical trials investigating various gene addition and gene editing strategies. Available results from a small number of patients, some with relatively short follow-up, are promising as a potentially curative strategy, with current efforts focused on continuing to improve the efficacy, durability, and safety of gene therapies for the cure of SCD.
Logistics, risks, and benefits of automated red blood cell exchange for patients with sickle cell disease
Authors: Kelly Shannon
Published: December 2023

Red blood cell (RBC) transfusions treat and prevent severe complications of sickle cell disease (SCD) and can be delivered as a simple or exchange transfusion. During an exchange, some of the patient's abnormal hemoglobin (Hb) S (HbS) RBCs are removed. An apheresis device can accomplish an automated RBC exchange, simultaneously removing patient’s RBCs while returning other blood components along with normal RBCs. Automated RBC exchange is therefore an isovolemic transfusion that can efficiently decrease HbS RBCs while limiting iron loading and hyperviscosity. However, specialized equipment, trained personnel, appropriate vascular access, and increased RBC exposure are required compared to simple or manual RBC exchange. Therefore, risks and benefits must be balanced to make individualized decisions for patients with SCD who require transfusion.
Challenges to successful outcomes in AYAs with ALL and potential solutions
Authors: Anandappa Annabelle , Curran Emily
Published: December 2023

Despite improvements in survival among pediatric patients with acute lymphoblastic leukemia (ALL), survival outcomes for adolescents and young adults (AYAs) with ALL have lagged. The reasons for the inferior outcomes among AYAs are multifactorial, each presenting unique challenges and requiring novel solutions. First, adverse disease biology is more common among AYAs with ALL. Ongoing trials are investigating novel approaches to treatment, such as incorporating JAK inhibitors for Philadelphia chromosome–like ALL, menin inhibitors for KMT2A-rearranged ALL, and BCL2/BCLXL inhibition for T-cell ALL. Poorer adherence to therapy also impedes improvements in survival outcomes for AYAs with ALL, but early data suggest that technology, both for monitoring and interventions, may be useful in increasing adherence among this population. Finally, better access to clinical trials and collaboration between pediatric and adult centers is critical in advancing the care of AYAs with ALL. Significant improvements have been made over the past decade, but recognizing, understanding, and addressing each of these unique challenges provides hope that the outcomes for AYAs will continue to improve even further.
Direct oral anticoagulants to treat deep venous thrombosis and pulmonary embolism in patients with cirrhosis: are we there yet?
Authors: Afzal Amber , Schaefer Jordan
Published: December 2023

A 59-year-old female with Child-Pugh class B cirrhosis attributed to nonalcoholic steatohepatitis complicated by hepatic encephalopathy, portal hypertension with esophageal varices, and thrombocytopenia is seen for management of an acute segmental right lower lobe pulmonary embolism in a clinic. She is hemodynamically stable. Complete blood count is notable for hemoglobin 11.6  g/dL and platelets 80 K/μL. Prothrombin time is 12.6 seconds; partial thromboplastin time, 33.7 seconds; and fibrinogen, 221  mg/dL. She was referred to discuss if a direct oral anticoagulant (DOAC) can be used for anticoagulation. What would you suggest?
Evaluation of increase in loss tangent from longitudinal vibration of wood log by considering apparent density difference between sapwood and heartwood caused by moisture content
Authors: Fukui Toshiyuki , Yanase Yoshiyuki , Fujii Yoshihisa
Published: December 2023

This study confirmed that the loss tangent (or tangent loss, tan δ) obtained from the longitudinal vibration of a wood log increases with the apparent density difference between sapwood and heartwood, owing to moisture content difference. The reason for this was estimated to be the shear stress occurring when the longitudinal vibration is excited from the calculation of the longitudinal vibration equation for a cylindrical model with different sapwood and heartwood densities. According to the measurement of the vibrational properties of 35 sugi (Cryptomeria japonica) logs with large moisture content variation in the sapwood and heartwood, the tan δ for longitudinal vibration increased compared with that for flexural vibration when the apparent sapwood density exceeded apparent heartwood density, whereas the difference in the specific dynamic Young’s modulus (E/ρ) was small. To discover why tan δ increases, both the axial and shear strain energy were calculated from the numerical solution of the longitudinal vibration of a cylindrical model by only considering the apparent density difference between sapwood and heartwood. It was found that the shear strain energy increases with the apparent density difference. Because it is known from previous studies that tan δ from the shear strain (tan δS) is larger than that from the axial strain (tan δA), this study concluded that tan δ increases with the apparent density difference. The ratio of increase of tan δ calculated by the model adequately explaange of the measured tan δ caused by the longitudinal vibration of a sugi log.
Establishment and Advances of Third-Generation Hybrid Rice Technology: A Review
Authors: Chen Zhufeng , Wu Jianxin , Deng Xing Wang , Tang Xiaoyan
Published: December 2023

Rice (Oryza sativa L.) is one of the most important food crops worldwide. The utilisation of heterosis (hybrid vigour) has played a significant role in increasing rice yield and ensuring food supply. Over the past 50 years, the first-generation three-line system based on cytoplasmic male sterility, and the second-generation two-line system based on environment-sensitive genic male sterility (EGMS), have been widely applied in hybrid rice production. However, the three-line system is restricted by the matching relationship among the three parental lines and allows only ~ 2–5% of germplasms to be explored for elite combinations. The environmental sensitivity of EGMS lines has posed serious risks to the production of hybrid seeds. These factors have hindered the development and applications of hybrid rice. Third-generation hybrid rice technology (TGHRT) is based on environment-insensitive genic male sterility, which can effectively overcome the intrinsic problems of the three-line and two-line systems. Since the establishment of TGHRT, numerous findings and innovations have been reported. This paper gives a brief review of traditional hybrid rice technologies and discusses the establishment of TGHRT, technical innovations in TGHRT, and future research that is necessary to promote the wide application of TGHRT in rice production.