bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex MEFV and MVK Variations in a Syrian Child: Implications for Clinical Phenotypes and Treatment Response—A Case Report
Authors: Kousa Alyamama , Ahmed Reem , Abu Bakr Mohammad Baraa , Aldosh Alaa Nouri , Khalil Basheer
Published: October 2024

This case report presents a 10-year-old Syrian boy with concurrent mutations in the Mediterranean fever ( MEFV) and mevalonate kinase ( MVK) genes, resulting in overlapping symptoms of Familial Mediterranean Fever (FMF) and Hyperimmunoglobulinemia D syndrome (HIDS), both classified as Periodic Fever Syndromes (PFSs). The co-occurrence of these mutations within a single individual is highly unusual. He presented with pallor, intermittent fever, and recurrent respiratory infections from an early age, along with anemia, splenomegaly, hepatomegaly, cervical lymphadenopathy, and growth failure noted in initial investigations. Still’s disease was initially considered as the most likely differential diagnosis, leading to the initiation of treatment with methylprednisolone; however, the parents did not follow-up with the treatment. The child returned at 5 years old with appendicitis, which was surgically removed, and parents reported recurrent episodes of arthralgia and joint swelling accompanied by nearly daily fever. Although the child experienced delayed motor development, his cognitive abilities were normal. Genetic analysis identified a homozygous likely pathogenic variant in the MVK gene and a heterozygous likely pathogenic variant in the MEFV gene. The child remains reliant on corticosteroids, with limited response to colchicine and improvement noted after transitioning from tocilizumab to infliximab. The latest follow-up demonstrated significant improvement with no fever, joint swelling, or lymphadenopathy; however, signs of growth failure persist. The atypical manifestations observed in this case may indicate a synergistic effect between the 2 mutations, contributing to the overall clinical picture. Therefore, although HIDS may dominate the clinical presentation, we cannot entirely dismiss the possibility that the FMF mutation plays a role in modulating these symptoms.
Concussion in Female Athletes of Contact Sports: A Scoping Review
Authors: Fahr Jana , Kraff Oliver , Deuschl Cornelius , Dodel Richard
Published: October 2024

Background:

Recent studies have described higher incidences of concussion, with more severe symptoms and worse outcomes in female athletes compared with male athletes.

Purpose:

To compile current knowledge about sex-specific differences in incidence, biomechanics, biomarkers, imaging, and outcomes of concussion in athletes participating in contact sports to better understand which fields should be explored in more detail.

Study Design:

Scoping review; Level of evidence, 3.

Methods:

The PubMed database was searched for articles published between January 2000 and November 2020 using the Medical Subject Headings terms “craniocerebral trauma” and “brain concussion” combined with the contact sports “football,”“soccer,”“hockey,” and “boxing.” Eligibility criteria were based on the recommendations of the Scottish Intercollegiate Guidelines Network. It focused on sex-specific differences within 5 major topics: (1) epidemiology, (2) biomechanics, (3) biomarkers, (4) imaging, and (5) specific concussion outcome variables, including neurocognitive performance, injury severity, and behavioral and psychological symptoms.

Results:

A total of 22 studies were included. Eight studies investigated the incidence of concussion, with 4 of the 8 finding a significantly higher incidence rate for female versus male athletes. Six studies that focused on biomechanics found that female athletes received fewer impacts with lower magnitudes. One study addressed biomarkers, showing that S100 calcium-binding protein B and neuron-specific enolase were increased after a game in female athletes, and the level of increase was similar to the changes found in male athletes. Based on the 3 imaging studies, affected brain tissue was greatest in areas associated with tau pathology in chronic traumatic encephalopathy. One study showed a lower hypointensity burden index after a season of ice hockey for female athletes, while another study showed more regions with white matter alterations. Seven studies examined concussion outcomes, with 4 studies showing more severe neuropsychological deficits; in addition, female athletes reported more and worse symptoms than male athletes.

Conclusion:

The results of this review indicated that female athletes had a higher risk of sustaining a concussion, although they received fewer impacts with lower magnitudes than male athletes. Biomarkers were able to be used equally for both sexes. Female athletes also had a higher neuropsychological deficit and increasingly worse symptoms after a concussion.
The Sino-Indian Rivalry and Balance-of-power Theory: Explaining India’s Underbalancing
Authors: Paul T. V.
Published: October 2024

Balance-of-power theory has been challenged as insufficient for explaining state behaviour. Powerful anomalies for the theory exist, especially among states confronting intense rivalry and war. One such anomaly is underbalancing in the Sino-Indian rivalry by the Indian side up until 2017. Today India is still engaged in limited hard balancing, relying on asymmetrical arms build-up and strategic partnership with the United States and Japan that are not equal to military alignment. This article argues that India has occasionally engaged in hard balancing, relying on arms build-up and limited alliance formation, but in general, there has been a serious effort not to resort to intense hard balancing by forming military alliances or symmetrical arms build-up. This calls for an explanation. The core argument I make is that the type of balancing is intimately related to the type of rivalry states have. The China– India rivalry has yet to become an intense existential variety compared to the India– Pakistan rivalry where existential security and protection of national identity are of major concern. Indian elite’s perceptions of the non-existential character of the Chinese threat and their reading of the Chinese strategy towards India have been the primary factors in explaining India’s balancing response. In the latter, active hard balancing has been occurring both internally and externally, whereas the former is characterised by a combination of limited hard balancing, soft-balancing and diplomatic engagement, components of a hedging strategy. The hard balancing has picked up momentum since 2017 in response to a more assertive strategy of the Xi Jinping regime as the Chinese government has ratcheted up military activity on the India–China border. The general implication is that rivals who do not fear existential threats need not engage in intense hard balancing. Perceptions of the threat level play a bigger role in what kind of balancing behaviour occurs in international politics than acknowledged in standard theories on balance of power, especially of the automatic balancing variety.
Reconsidering the Relationship between Incarceration, Trust in the State, Community Engagement, and Civic Participation
Authors: Yi Youngmin , Enns Peter K. , Wildeman Christopher
Published: October 2024

Scholars have reached different conclusions about the relationship between carceral contact and community engagement and civic participation. We offer a theoretical account that aims to synthesize this work to argue that incarceration should depress trust in the state but may increase, decrease, or produce no substantial effect on community or civic engagement, leading to no overall average association. We use data from the Family History of Incarceration Survey (FamHIS), a nationally representative survey of adults in the United States (n = 2,703) to conduct an expansive test of associations between direct (own) and indirect (family member) incarceration and trust in the state, civic participation, and community engagement. Our findings show that incarceration may not uniformly depress political and civic behaviors, on average. Furthermore, they inform our understanding of seemingly divergent conclusions in prior research, underscoring potential variability of prosocial actions and their enabling and constraining conditions in the wake of carceral contact.
“The System Is So Messed up”: Neutrality and Efficiency in an Eviction Courtroom
Authors: Kepes Jacob Scott , Kempler Alex M.
Published: October 2024

Eviction research focuses primarily on what happens before or after an eviction, overlooking the importance of the courtroom in understanding how the eviction process unfolds. We offer a case study of an eviction court in Franklin County, Ohio, during the height of the COVID-19 pandemic. Using ethnographic observation and qualitative interviews, we investigate the following questions: (1) What role do courtroom actors play in eviction procedures? and (2) How have the COVID-19 pandemic and pandemic-related policy impacted courtroom processes? We highlight this court’s determination to continue business as usual, as demonstrated through allegiance to the logics of neutrality and efficiency. Although the court was able to implement small-scale changes, these changes were made in the interest of landlords, ultimately undermining the court’s supposed neutrality and enforcing a type of efficiency that favored the continued processing of cases despite warnings from public health officials.
Electoral dynamics, the construction of a common sense and national urban policies: The case of the radical right vote in the 2002 French presidential election
Authors: de Santos Barbosa Joaquín , Oosterlynck Stijn
Published: October 2024

The main theories of urban governance analysis do not take a significant interest in elections. As a result, the existing literature has seldom meaningfully engaged with electoral dynamics. This article seeks to put electoral dynamics at the centre of urban governance analysis. We examine the case of France and its Politique de la Ville, the national urban policy targeted towards the banlieues – the working-class neighbourhoods at the periphery of French cities. We aim to explain how a major reform of this policy in 2003 came about in the aftermath of the 2002 French presidential election, where a radical right candidate progressed to the second round of the election for the first time in history. By taking Gramsci’s notion of ‘common sense’ as a starting point and dwelling on critical approaches to electoral processes, this article examines the construction of the discourse on the banlieues during the campaign through analysing the media and political debates. It shows how this discourse shaped the interpretation of the election’s outcome and provided a political opportunity to justify a major reform of the policy. We conclude by calling for a more careful examination of electoral dynamics, and deconstruction of the common sense discourses underpinning their interpretation.
Use of a Low Profile Ultra-High Molecular Weight Polyethylene Diaphyseal Humeral Cement Restrictor in Shoulder Arthroplasty
Authors: Bond Elizabeth C , Finley Suzanne , Pennington Elizabeth , Reinke Emily K , McGarvey Lewis , Garrigues Grant E , Lassiter Tally E , Anakwenze Oke A
Published: October 2024

Background

When implanting a cemented humeral stem, a reliable method to prevent inappropriate extension and enable pressurization of cement in the intramedullary canal is required. The aim was to assess the outcomes of a dedicated humeral diaphyseal cement restrictor.

Methods

In total 218 shoulders (207 patients) were included in the study, all of whom underwent a cemented total shoulder arthroplasty and a retrospective review was performed. The primary outcomes of interest were device stability in the medullary canal, successful occlusion of the canal, cement extrusion and quality of cement mantle.

Results

The majority of the cohort was female (63.3%) males and the average patient age was 71.7 years (SD 8.45). In 81.7% the device was deemed to be stable in the medullary canal. The device was significantly more stable in primary (84.2%) compared to revision cases (64.3%, p = 0.02). In 69.7% Barrack grade A mantle quality was achieved, this was higher in primary cases (74.2%) compared to revision cases (39.3%) (p = 0.00006).

Discussion

We noted excellent cementation outcomes using a cement restrictor specifically designed for the diaphyseal humerus anatomy. However, this humeral specific restrictor was noted to be more stable in primary as compared to revision cases.
A Cautionary Note on Using Univariate Methods for Meta-Analytic Structural Equation Modeling
Authors: Jak Suzanne , W.-L. Cheung Mike
Published: October 2024

Meta-analytic structural equation modeling (MASEM) is an increasingly popular technique in psychology, especially in management and organizational psychology. MASEM refers to fitting structural equation models (SEMs), such as path models or factor models, to meta-analytic data. The meta-analytic data, obtained from multiple primary studies, generally consist of correlations across the variables in the path or factor model. In this study, we contrast the method that is most often applied in management and organizational psychology (the univariate-r method) to several multivariate methods. “Univariate-r” refers to performing multiple univariate meta-analyses to obtain a synthesized correlation matrix as input in an SEM program. In multivariate MASEM, a multivariate meta-analysis is used to synthesize correlation matrices across studies (e.g., generalized least squares, two-stage SEM, one-stage MASEM). We conducted a systematic search on applications of MASEM in the field of management and organizational psychology and showed that reanalysis of the four available data sets using multivariate MASEM can lead to different conclusions than applying univariate-r. In two simulation studies, we show that the univariate-r method leads to biased standard errors of path coefficients and incorrect fit statistics, whereas the multivariate methods generally perform adequately. In the article, we also discuss some issues that possibly hinder researchers from applying multivariate methods in MASEM.
View of intensive care units nurses toward factors related to missed nursing
Authors: Eghbali Tayebeh , Ahmadi Nejad Mehdi , Dehghan Mahlegha , Maazallahi Mahboobeh , Rahiminezhad Elham , Azizzadeh Forouzi Mansooreh
Published: October 2024

Background

Missed nursing care is defined as aspects of care needed by patients that are completely or partially omitted or significantly delayed. Various factors may lead to missed care. Investigating factors related to missed care and their occurrence can prevent or minimize risks to patient safety. The present study was conducted to investigate factors related to missed nursing care in intensive care units.

Method

This was a descriptive cross-sectional study. The study sample comprised 255 nurses working in the intensive care units of Kerman University of Medical Sciences. Questionnaires regarding demographic characteristics and factors related to missed nursing care were used to collect data. Descriptive statistics (mean and standard deviation) and inferential statistics (independent t-tests and one-way analysis of variance) were employed for data analysis.

Results

The mean score of factors related to missed nursing care was 77.63 ± 63.13 (ranging from 20 to 80), which exceeded the average score of the questionnaire (30). The highest mean scores for factors related to missed care were observed for “lack of nursing staff,” “malfunction of equipment when needed,” and “emergency conditions of patients (e.g., deterioration of the patient's condition)” respectively. The lowest mean score was associated with “tension or poor communication with other aid and support centers” and “tension or weak communication within the nursing team.”

Conclusions

Based on the findings, providing mental and physical support, ensuring adequate facilities, and hiring skilled and experienced caregivers can help reduce instances of missed nursing care.
Reimagining HR Issues in Startup: Roadmap to Success
Authors: Potukuchi Sudhakar , Thakur Sumita
Published: October 2024

In the evolving startup landscape, formal human resource (HR) processes may be perceived as slowing down decision-making and adding unnecessary costs. By reimagining competencies and aligning with the different stages of startup’s journey, HR can become a valuable business partner. Different stages of a startup are explained by conceptualising a framework ‘SCIENT’; each letter of this framework represents a distinct phase, namely Solution to a problem, Customer Value Proposition, Investors, Ecosystem, Novelty and Team. At each of these phases, the pivotal role played by HR in facilitating diverse perspectives, learning from failures, promoting diversity and culture of innovation, and adopting digital solutions for talent management are discussed. The article concludes by emphasising the dynamic and unique nature of these issues, calling for a reimagined role of HR in ensuring the success of startups.
Building a Resilient Workforce: Tackling HR Challenges in a Startup Environment
Authors: Sahal Hemant , Ranolia Vaishali
Published: October 2024

Indian startups have significantly changed the face of India’s job market, given the number of jobs created by Indian startups has risen exponentially. Startups face significant challenges in maintaining organisational culture for long-term success due to several factors inherent in their dynamic environment. Hence, startups must prioritise the establishment of a resilient workforce. In this article, we will be highlighting critical challenges: rapid scaling and talent acquisition, leadership development in a non-hierarchical environment, performance management and retention amidst high turnover rates, learning and growth opportunities, legal compliance and regulatory hurdles, among others. We will also discuss how startups can cultivate a culture of adaptability by empowering employees to excel in the face of uncertainty.
Startup Quest: Decoding the Journey from Hire to Inspire—Unveiled Snippets in Indian Context
Authors: Bhattacharyya Sreeparna
Published: October 2024

This article explores the significance of human resource (HR) practices in Indian startups, with a specific emphasis on recruiting practices and its influence on organisational culture, productivity, and employee satisfaction. The article emphasises the nation’s conducive environment, and the proficient pool of qualified individuals, with a special emphasis on fresh MBA graduates and their successful narratives in different startups. HR practices play a crucial role in organisations, specifically in startups, in developing recruiting tactics that are specifically designed for the business life cycle to create their employer branding. The article highlights the need to ensure that recruiting procedures are in line with the aims and values of the organisation. Additionally, it underscores the relevance of prioritising employee well-being, work-life balance and career development to cultivate a favourable workplace culture. Three real-life situations in three different startups, which differ not only in their sizes but also in levels (local, national and multinational), exemplify the influence of strategic recruitment on employee contentment and the achievement of organisational objectives. Thorough recruiting procedures draw in skilled individuals who share the company’s vision and values, promoting possibilities for professional development and establishing vibrant work atmospheres. To summarise, this article emphasises the crucial significance of strategic HR practices in influencing the culture, productivity and development path of Indian startups. Startups may use the potential of their human resources to foster innovation, enhance competitiveness and achieve sustained success in the dynamic business environment by placing emphasis on efficient recruiting tactics and cultivating a supportive workplace culture.
Technology: The Cornerstone of HR Service Delivery in the Startup Ecosystem
Authors: Ranjan Ramesh
Published: October 2024

In the fast-evolving startup ecosystem, where agility and innovation are paramount, human resources (HR) is often neglected in the initial stages due to resource constraints and a lack of understanding of its strategic role. However, as startups scale, the need for a structured approach to HR becomes evident. Digital transformation and artificial intelligence (AI) are revolutionising HR service delivery in startups, enabling them to manage HR functions effectively without extensive HR teams. Cloud-based HR platforms and AI-driven tools streamline various HR processes, from recruitment and onboarding to performance management and employee engagement. While challenges like data security and employee acceptance exist, implementing digital HR strategically can provide startups with a competitive edge in attracting and retaining top talent, fostering a positive work environment and driving sustainable growth. The future of HR in startups lies in a collaboration between AI and HR professionals, leveraging technology’s power while maintaining an ethical and people-centric approach.
Unlocking compassion: expanding access to palliative care in Saudi Arabia
Authors: Almobarak Fhaied
Published: October 2024

Background:

Palliative care is an essential element of the healthcare system. It has profound benefits for patients with life-limiting illnesses. The Saudi Arabian healthcare system lags in integrating this vital component effectively. Hence, estimating the palliative care needs of the Saudi Arabian population is crucial to understanding the country’s demand for palliative care.

Aim:

To assess the past trends in adult palliative care needs in Saudi Arabia.

Methods:

The current research used population-based secondary data analysis by employing two palliative care needs estimation methods: the direct or fixed estimation method by Gómez-Batiste and the maximum or maximal method by Murtagh and Rosenwax. The estimated palliative care needs were stratified by gender.

Results:

An upward trend in the palliative care needs of the Saudi Arabian population is evident through the estimation techniques. The proportion of palliative care needs relative to deaths climaxed at 95% in the observed years. By 2022, the number of people requiring palliative care skyrocketed to 79,725 (fixed method) and 101,623 (maximal method).

Conclusion:

The need for palliative care in Saudi Arabia substantially rose in the observed years. It is inevitable to bridge the gap between palliative care needs and supply with advanced integration of palliative care services in the national healthcare system.
Move over and make space for lived experience criminology: Why we do “lived experience”
Authors: Antojado Dwayne , McPhee Tina
Published: October 2024

This paper points out the disparity in the recognition of lived experiences between the United States – where convict criminology is more established, and Australia. The authors call for a shift from convict to lived experience criminology in Australia, emphasising the need for diverse methodologies beyond autoethnography. It is pertinent to note here that the authors of this paper, Antojado and McPhee, are formerly incarcerated scholars, serving time in various prisons in Australia. We use our expertise by experience to inform our work. This paper discusses the challenges individuals with lived prison and/or criminal legal sanction experience (LPCLSE) face in gaining academic recognition and critiques the academic community's hesitance to accept us as equals. It stresses the significance of lived experiences in deepening the understanding of the social and emotional aspects of crime and justice. Integrating these narratives into criminology is argued to challenge and enrich present epistemological frameworks, leading to more holistic and empathetic research and policy-making in the criminal legal sector. The authors advocate for redefining criminological expertise to value experience equally with academic qualifications and call for academic support for the development of lived experience criminology. This is seen as crucial for a more inclusive and comprehensive understanding of crime and justice discourses, urging criminologists to embrace and develop this subfield. Using the work of bell hooks and Dean Spade, we also turn our attention to the reasons for why people with lived experience expertise might engage in this type of work, arguing that it is a way for us to make/unmake meaning, to live with purpose, to live with guilt, and to love.
Mapping the future: A scoping analysis of paediatric content in Australian paramedic curriculum
Authors: Peasey Rachel , Ross Linda , McCartan Julia , Bowles Kelly-Ann
Published: October 2024

Introduction

The rise of formal degree programs has significantly expanded professional and independent paramedicine systems globally. Paramedicine now includes a wide range of responsibilities, from managing life-threatening conditions to addressing diverse patient needs. However, current education frameworks often lack specificity, being largely adapted from other clinical disciplines. This study aims to provide a comprehensive description of the current state of undergraduate paramedic education concerning paediatric content in Australia.

Methods

A content analysis was conducted on publicly available curriculums from accredited Australian universities offering Bachelor of Paramedicine programs. Initial data analysis involved searching for paediatric terminology in learning outcomes and/or synopses. Subsequent analysis of curricula from institutions that completed member checking comprised two components: a descriptive arm to quantitatively assess paediatric education and an inductive arm to qualitatively explore categories of paediatric curriculum.

Results

Curriculum of 15/16 programs were searched, revealing a median of three units which included paediatric terminology in learning outcomes or unit synopses. Four institutions across five Australian states completed member checking, revealing a national median paediatric content inclusion of 0%. Only 32% of units included any paediatric content, with a median inclusion of 10%. Examination of the hidden aspects of curriculum highlighted discrepancies between learning outcomes and paediatric content percentages. No overarching degree learning outcomes mentioned paediatrics. Unit learning outcomes that had paediatric mention were categorised into three groups: content, conceptual understanding and skills development. Additionally, distribution analysis revealed a notable emphasis on non-technical skills, potentially overshadowing core knowledge essential for paediatric care.

Discussion

The findings underscore the need for curriculum reform, to enhance paramedic student preparedness to manage paediatrics. Scaffolding paediatric content into the curriculum could foster a comprehensive understanding of patient care and mitigate disparities in paediatric management. Collaboration with stakeholders and innovative teaching methodologies hold promise for advancing paediatric education in paramedicine.
Grassroots resistance against hydropower dams: Community campaigns and civilian-rebel cooperation in Myanmar
Authors: Kim Kyungmee
Published: October 2024

When large hydropower dams are planned in conflict-affected regions, these projects can exacerbate pre-existing tensions and conflicts. This article focuses on the conflicts surrounding Myanmar’s controversial Myitsone and Hatgyi dam projects. Drawing on extensive fieldwork, the findings demonstrate how politicized identities influence local mobilization and grassroots efforts to resist dams amid violent conflicts. Comparative analysis reveals the multifaceted nature of resistance mobilization in conflict settings, highlighting the role of ethnic solidarity, identity-based framing, alliance building, and social imaginaries. In both cases, civil society activists sought to generate support among co-ethnic populations by invoking their shared lived experiences and suffering from protracted conflicts. This framing succeeded in amplifying emotions and solidarity, and strengthening grassroots resistance. In addition, powerful ethnic resistance organizations lent their support to opposing dams, thereby boosting the significance of the resistance. However, the involvement of armed groups can undermine cooperation between civilian populations living under different political authorities, as shown in the Hatgyi case. Differing social imaginaries of a river—whether it is considered nationally significant or peripheral—have distinct political ramifications for resistance. The article underscores the centrality of underlying social psychological processes as the drivers of local resistance and environmental conflicts in conflict settings.
Proactive personality and behavior: Opportunities for refining theory and creating a more unified understanding
Authors: Crant J. Michael , Chen Nancy
Published: October 2024

Proactive personality and behavior are frequently studied constructs in the organizational behavior and industrial-organizational psychology literatures. While much is known regarding main effects, mediators, and moderators, there are opportunities for further empirical work to develop and advance theory in these areas. In this editorial, we provide a brief overview of the theoretical foundations of both literatures and offer guidance for theory refinement consistent with the mission of the Journal of Management Scientific Reports. Topics covered are (1) opportunities for empirical research that tests, extends, or refines existing theory on proactivity; (2) empirical research aimed at enhancing the precision of measurement and rigor in proactivity research; and (3) using meta-analysis to improve theoretical understanding of proactivity.
Gene therapy in transfusion-dependent non-β0/β0 genotype β-thalassemia: first real-world experience of beti-cel
Authors: Mirza Adil , Ritsert Mona-Lisa , Tao Gloria , Thakar Himal , Lobitz Stephan , Heine Sabine , Koscher Leila , Dürken Matthias , Schmitt Anita , Schmitt Michael , Pavel Petra , Laier Sascha , Jakoby Donate , Greil Johann , Kunz Joachim , Kulozik Andreas
Published: October 2024

Gene addition and editing strategies for transfusion-dependent β-thalassemia have gained momentum as potentially curative treatment options, with studies showcasing their efficacy and safety. We report, to our knowledge, the first real-world application of betibeglogene autotemcel (beti-cel; Zynteglo) during its period of active license in Europe from January 2020 to March 2022 for patients aged ≥12 years without a β0/β0 genotype and without a HLA-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder because of nonsafety reasons. Among 15 screened patients, 4 opted out for fertility and safety concerns, 2 were excluded because of marked hepatic siderosis, and 1 had apheresis collection failure. Eight patients received beti-cel after busulfan myeloablative conditioning, all achieving transfusion independence within 8 to 59 days, with posttreatment hemoglobin levels ranging from 11.3 to 19.3 g/dL. No deaths occurred, but acute toxicity mirrored busulfan’s known effects. Posttreatment platelet management faced challenges because of HLA-antibodies in 3 patients. Monitoring up to month 24 revealed pituitary-gonadal endocrine dysfunction in all 3 female and in 2 of 5 male patients. Additionally, we observed unexpected posttreatment sequelae: 1 patient developed polycythemia that could not be explained by known genetic or acquired mechanisms, 1 patient developed posttreatment depression and anxiety prohibiting her from returning to work, and 1 patient developed fatigue severely compromising both quality of life and work capacity. This real-world experience corroborates beti-cel’s efficacy and safety and provides information on adverse events observed during real-world use of the therapy.
Midostaurin shapes macroclonal and microclonal evolution of FLT3-mutated acute myeloid leukemia
Authors: Joudinaud Romane , Boudry Augustin , Fenwarth Laurène , Geffroy Sandrine , Salson Mikaël , Dombret Hervé , Berthon Céline , Pigneux Arnaud , Lebon Delphine , Peterlin Pierre , Bouzy Simon , Flandrin-Gresta Pascale , Tavernier Emmanuelle , Carre Martin , Tondeur Sylvie , Haddaoui Lamya , Itzykson Raphael , Bertoli Sarah , Bidet Audrey , Delabesse Eric , Hunault Mathilde , Récher Christian , Preudhomme Claude , Duployez Nicolas , Dumas Pierre-Yves
Published: October 2024

Despite the use of midostaurin (MIDO) with intensive chemotherapy (ICT) as frontline treatment for Fms-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), complete remission rates are close to 60% to 70%, and relapses occur in >40% of cases. Here, we studied the molecular mechanisms underlying refractory/relapsed (R/R) disease in patients with FLT3-mutated AML. We conducted a retrospective and multicenter study involving 150 patients with R/R AML harboring FLT3–internal tandem duplication (ITD) (n = 130) and/or FLT3–tyrosine kinase domain mutation (n = 26) at diagnosis assessed by standard methods. Patients were treated with ICT + MIDO (n = 54) or ICT alone (n = 96) according to the diagnosis date and label of MIDO. The evolution of FLT3 clones and comutations was analyzed in paired diagnosis–R/R samples by targeted high-throughput sequencing. Using a dedicated algorithm for FLT3-ITD detection, 189 FLT3-ITD microclones (allelic ratio [AR] of <0.05) and 225 macroclones (AR ≥ 0.05) were detected at both time points. At R/R disease, the rate of FLT3-ITD persistence was lower in patients treated with ICT + MIDO than in patients not receiving MIDO (68% vs 87.5%; P = .011). In patients receiving ICT + MIDO, detection of multiple FLT3-ITD clones was associated with a higher FLT3-ITD persistence rate at R/R disease (multiple clones: 88% vs single clones: 57%; P = .049). If only 24% of FLT3-ITD microclones detected at diagnosis were retained at relapse, 43% became macroclones. Together, these results identify parameters influencing the fitness of FLT3-ITD clones.
Integrated respiratory care: what forms may it take and what are the benefits to patients?
Authors: Patel I.
Published: October 2024

Educational aims

To outline the rationale behind and key components of integrated respiratory care.

To give an overview of different models of delivery of integrated respiratory care.

To explore the benefits to patients with chronic respiratory disease.

Providing for the long-term needs of patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), sets new challenges for healthcare organisations in terms of structure and funding. Integrated respiratory care is a holistic patient-centred approach to long-term conditions encompassing: disease prevention and promotion of lung health; early diagnosis; monitoring and education; coordination of hospital and community care; and implementation of evidence-based guidelines. Models of integrated respiratory care may vary depending on local resources and needs. Key aspects include nurse-led care nearer to or in the patients' home, self-management support, flexible healthcare design that suits patient needs, effective information sharing, and access to specialist care. These interventions have the potential to improve self-care and understanding of disease, reduce the need for scheduled and unscheduled consultations and length of stay, and enhance patients' health-related quality of life.
Research progress of ankyrin repeat domain 1 protein: an updated review
Authors: Xu Xusan , Wang Xiaoxia , Li Yu , Chen Riling , Wen Houlang , Wang Yajun , Ma Guoda
Published: October 2024

Ankyrin repeat domain 1 (Ankrd1) is an acute response protein that belongs to the muscle ankyrin repeat protein (MARP) family. Accumulating evidence has revealed that Ankrd1 plays a crucial role in a wide range of biological processes and diseases. This review consolidates current knowledge on Ankrd1’s functions in myocardium and skeletal muscle development, neurogenesis, cancer, bone formation, angiogenesis, wound healing, fibrosis, apoptosis, inflammation, and infection. The comprehensive profile of Ankrd1 in cardiovascular diseases, myopathy, and its potential as a candidate prognostic and diagnostic biomarker are also discussed. In the future, more studies of Ankrd1 are warranted to clarify its role in diseases and assess its potential as a therapeutic target.
Tinnitus is associated with increased extracellular matrix density in the auditory cortex of Mongolian gerbils
Authors: Tziridis Konstantin , Maul Antonia , Rasheed Jwan , Krauss Patrick , Schilling Achim , Schulze Holger
Published: October 2024

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals’ ACs compared to NT or C animals’ cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus.
Exploring bias risks in artificial intelligence and targeted medicines manufacturing
Authors: Nwebonyi Ngozi , McKay Francis
Published: October 2024

Background

Though artificial intelligence holds great value for healthcare, it may also amplify health inequalities through risks of bias. In this paper, we explore bias risks in targeted medicines manufacturing. Targeted medicines manufacturing refers to the act of making medicines targeted to individual patients or to subpopulations of patients within a general group, which can be achieved, for example, by means of cell and gene therapies. These manufacturing processes are increasingly reliant on digitalised systems which can be controlled by artificial intelligence algorithms. Whether and how bias might turn up in the process, however, is uncertain due to the novelty of the development.

Methods

Examining stakeholder views across bioethics, precision medicine, and artificial intelligence, we document a range of opinions from eleven semi-structured interviews about the possibility of bias in AI-driven targeted therapies manufacturing.

Result

Findings show that bias can emerge in upstream (research and development) and downstream (medicine production) processes when manufacturing targeted medicines. However, interviewees emphasized that downstream processes, particularly those not relying on patient or population data, may have lower bias risks. The study also identified a spectrum of bias meanings ranging from negative and ambivalent to positive and productive. Notably, some participants highlighted the potential for certain biases to have productive moral value in correcting health inequalities. This idea of “corrective bias” problematizes the conventional understanding of bias as primarily a negative concept defined by systematic error or unfair outcomes and suggests potential value in capitalizing on biases to help address health inequalities. Our analysis also indicates, however, that the concept of “corrective bias” requires further critical reflection before they can be used to this end.
Inconsistent values and algorithmic fairness: a review of organ allocation priority systems in the United States
Authors: Dale Reid , Cheng Maggie , Pines Katharine Casselman , Currie Maria Elizabeth
Published: October 2024

Background

The Organ Procurement and Transplant Network (OPTN) Final Rule guides national organ transplantation policies, mandating equitable organ allocation and organ-specific priority stratification systems. Current allocation scores rely on mortality predictions.

Methods

We examined the alignment between the ethical priorities across organ prioritization systems and the statistical design of the risk models in question. We searched PubMed for literature on organ allocation history, policy, and ethics in the United States.

Results

We identified 127 relevant articles, covering kidney (19), liver (60), lung (24), and heart transplants (23), and transplant accessibility (1). Current risk scores emphasize model performance and overlook ethical concerns in variable selection. The inclusion of race, sex, and geographical limits as categorical variables lacks biological basis; therefore, blurring the line between evidence-based models and discrimination. Comprehensive ethical and equity evaluation of risk scores is lacking, with only limited discussion of the algorithmic fairness of the Model for End-Stage Liver Disease (MELD) and the Kidney Donor Risk Index (KDRI) in some literature. We uncovered the inconsistent ethical standards underlying organ allocation scores in the United States. Specifically, we highlighted the exception points in MELD, the inclusion of race in KDRI, the geographical limit in the Lung Allocation Score, and the inadequacy of risk stratification in the Heart Tier system, creating obstacles for medically underserved populations.

Conclusions

We encourage efforts to address statistical and ethical concerns in organ allocation models and urge standardization and transparency in policy development to ensure fairness, equitability, and evidence-based risk predictions.
Effectiveness and efficiency of immunisation strategies to prevent RSV among infants and older adults in Germany: a modelling study
Authors: Krauer Fabienne , Guenther Felix , Treskova-Schwarzbach Marina , Schoenfeld Viktoria , Koltai Mihaly , Jit Mark , Hodgson David , Schneider Udo , Wichmann Ole , Harder Thomas , Sandmann Frank G. , Flasche Stefan
Published: October 2024

Background

Recently, several novel RSV immunisation products that protect infants and older adults against RSV disease have been licensed in Europe. We estimated the effectiveness and efficiency of introducing these RSV immunisation strategies in Germany.

Methods

We used a Bayesian framework to fit a deterministic age-structured dynamic transmission model of RSV to sentinel surveillance and RSV-specific hospitalisation data in Germany from 2015 to 2019. The calibrated model was used to evaluate different RSV intervention strategies over 5 years: long-acting, single-dose monoclonal antibodies (mAbs) in high-risk infants aged 1–5 months; long-acting mAbs in all infants aged 1–5 months; seasonal vaccination of pregnant women and one-time seasonal vaccination of older adults (75 + /65 + /55 + years). We performed sensitivity analysis on vaccine uptake, seasonal vs. year-round maternal vaccination, and the effect of under-ascertainment for older adults.

Results

The model was able to match the various RSV datasets. Replacing the current short-acting mAB for high-risk infants with long-acting mAbs prevented 1.1% of RSV-specific hospitalisations in infants per year at the same uptake. Expanding the long-acting mAB programme to all infants prevented 39.3% of infant hospitalisations per year. Maternal vaccination required a larger number to be immunised to prevent one additional hospitalisation than a long-acting mAB for the same uptake. Vaccination of adults older than 75 years at an uptake of 40% in addition to Nirsevimab in all infants prevented an additional 4.5% of all RSV hospitalisations over 5 years, with substantial uncertainty in the correction for under-ascertainment of the RSV burden.

Conclusions

Immunisation has the potential to reduce the RSV disease burden in Germany.
Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease
Authors: Rai Amit Kumar , Muthukumaran Natarajaseenivasan Suriya , Nisini Noemi , Lee Tiffany , Kyriazis Ioannis D. , de Lucia Claudio , Piedepalumbo Michela , Roy Rajika , Uchida Shizuka , Drosatos Konstantinos , Bisserier Malik , Katare Rajesh , Goukassian David , Kishore Raj , Garikipati Venkata Naga Srikanth
Published: October 2024

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2–4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions. However, their role in ischemic heart disease in DM remains poorly understood. We provide new insights into the lncRNA expression profile after ischemic heart disease in DM mice. We performed unbiased RNA sequencing of well-characterized type 2 DM model db/db mice or its control db/+ subjected to sham or MI surgery. Computational analysis of the RNA sequencing of these LV tissues identified several differentially expressed lncRNAs between (db/db sham vs. db/db MI) including Gm19522 and Gm8075. lncRNA Gm-19522 may regulate DNA replication via DNA protein kinases, while lncRNA Gm-8075 is associated with cancer gene dysregulation and PI3K/Akt pathways. Thus, the downregulation of lncRNAs Gm19522 and Gm8075 post-MI may serve as potential biomarkers or novel therapeutic targets to improve cardiac repair/recovery in diabetic ischemic heart disease.
Parvimonas micra forms a distinct bacterial network with oral pathobionts in colorectal cancer patients
Authors: Löwenmark Thyra , Köhn Linda , Kellgren Therese , Rosenbaum William , Bronnec Vicky , Löfgren-Burström Anna , Zingmark Carl , Larsson Pär , Dahlberg Michael , Schroeder Bjoern O. , Wai Sun Nyunt , Ljuslinder Ingrid , Edin Sofia , Palmqvist Richard
Published: October 2024

Background

Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum.

Methods

In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95).

Results

We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC.

Conclusions

Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.