bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of carotenoids from red mamey fruit (Pouteria sapota) against amyloid-β monomers in Alzheimer's disease: Computational analysis and ADMET prediction
Authors: Orjuela Adrián L , Pecchio Marisín , Cruz-Mora Jessica , Emani Lakshmi Sowmya , Carreira Maria B , Larionov Oleg V , Hegde Muralidhar L , Rao K S Jagannatha , Alí-Torres Jorge , Lakey-Beitia Johant
Published: November 2024

Background

Carotenoids, potent antioxidants in fruits and vegetables, have recently garnered attention for their potential therapeutic effects against neurodegenerative diseases. This study focuses on the interaction and anti-aggregation properties of conventional and unconventional carotenoids found in red mamey fruit, a nutraceutical fruit that is a rich source of these compounds.

Objective

To assess computational the interaction between of amyloid-β (Aβ) peptide with a set of carotenoids and three carotenoids previously explored in experimental assays as well as to assess ADMET prediction of carotenoids selected by computational analysis results.

Methods

We analyzed the interaction between these carotenoids and Aβ peptides using molecular docking, a key factor in Alzheimer's disease (AD) pathology. Selected carotenoids were compared with the reference compounds cryptocapsin (1), zeaxanthin (2), lutein (3), and cryptocapsin-5,6-epoxide (24), which previously demonstrated significant anti-aggregation activity against Aβ. Using SwissADME and ADMET Predictor® software to determine the pharmaceutical analysis prediction.

Results

Computational analysis identified (5R,8R)-sapotexanthin-5,8-epoxide (19) and (5S,8S)-cryptocapsin-5,8-epoxide (26) as the most promising candidates due to their strong binding affinity and potential anti-aggregation properties against Aβ. The pharmaceutical analysis identified compounds (5S,8S)-cryptocapsin-5,8-epoxide (26) and (5R,8R)-cryptocapsin-5,8-epoxide (28) as the most promising compounds. Our findings suggest that specific modifications in the carotenoid structure, particularly modifications in the type of epoxidation and stereochemistry, can significantly influence the biological activity of carotenoids and biopharmaceutical performance.

Conclusions

These results provide valuable insights for future in vitro studies of most potential carotenoids (19 and 26) and the development of potential therapeutic agents for AD.
Ensuring continuity of care in times of crisis: A longitudinal analysis of dementia care delivery during armed conflict
Authors: Radomyslsky Zorian , Kivity Sara , Alon Yaniv , Saban Mor
Published: November 2024

Background

Individuals with dementia are particularly vulnerable during emergency situations due to challenges with cognition, mobility, and daily functioning. However, little is known about how disruptive events may specifically impact the health of those with dementia.

Objective

To evaluate changes in health outcomes for individuals with and without dementia surrounding the Israel-Gaza war in October 2023. Specifically, we analyzed and compared changes in mental health status, medication adherence, healthcare service utilization, and associated costs between individuals with dementia (Study Group) and those without dementia (Control Group) during the period surrounding the Israel-Gaza war in October 2023.

Method

A prospective cohort study compared outcomes between individuals with dementia (Study Group, n = 24,178) and without (Control Group, n = 250,652) before and after the crisis onset. The conflict precipitously threw national systems into disarray, recruited healthcare personnel to the war effort, and disrupted supply chains.

Results

Compared to baseline, analysis revealed alterations in patterns of dementia diagnoses, healthcare service utilization, medication adherence, and associated costs during the crisis period for both groups. However, the Study Group experienced comparatively larger declines.

Conclusions

Findings provide insights into how humanitarian emergencies, through disruption of health systems and care networks, differentially impact continuity of dementia care. This underscores the need for tailored crisis response strategies to address the heightened vulnerabilities of patients with dementia.
A diverting quarter century? Evidence-based police-led diversion 25 years on
Authors: Neyroud Peter
Published: November 2024

It is more than 25 years since Lawrence Sherman delivered his ‘Ideas in American Policing’ lecture on ‘evidence-based policing’ for the US Police Foundation. The original work [Sherman LW (1998) Evidence-Based Policing. Ideas in American Policing. Washington, DC: Police Foundation], Sherman’s equally seminal study on ‘preventing crime’ [Sherman LW, Gottfredson D, MacKenzie D, et al. (1997) Preventing Crime: What Works, What Doesn’t, What’s Promising. Washington, DC: Office of Justice Programs] and the subsequent development of evidence-based policing in the ‘Triple T’ [Sherman LW (2013) The rise of evidenced-based policing: targeting, testing and tracking. In: Tonry M (ed.) Crime and Justice in America 1975–2025. Chicago: University of Chicago Press] have been immensely influential as well as, for some, controversial. In 1998, Sherman challenged scholars, practitioners and policymakers to use the ‘best available evidence’ to guide policy and practice. He then posed four questions: ‘What is it? What is new about it? How does it apply to a specific example of police practice? How can it be institutionalized?’. Taking the lead from Sherman's questions, this contribution to the 25-year anniversary collection focuses on one example – police-led diversion – to illustrate the development and challenges of institutionalizing evidence-based policing since 1998.
The role of the press in reproducing the climate action contrarian framings of European think tanks
Authors: Moreno Jose A.
Published: November 2024

This article lies in the field of research on communication and obstructionism towards climate action. The research addresses the role of the press in reproducing framings hostile to climate action when quoting some European think tanks the literature has identified as disseminators of climate obstructionist messages. The methodology is based on content and framing analysis, covering all European newspapers that have mentioned the five selected think tanks. The analysis comprises the study of 1516 texts extracted from 203 European newspapers listed on the Factiva platform. The results show that most of the press coverage about these organizations reproduced their frames against climate action, although this reproductive coverage decreased over time. Among these frames, those with political content predominated over those with climate science content. In particular, frames attacking the climate movement and questioning policies for being harmful or ineffective overshadowed scientific questioning. The research also includes a gender component in the analysis of the authorship of the texts, which shows that texts by male authors were slightly more likely to reproduce climate obstructionism than those by female authors. Ultimately, this study contributes to the discussion on the role of journalism in amplifying climate action contrarian discourse.
Influence of cavity and ramp layout on combustion performance in a strut-based scramjet combustor
Authors: Atci Metehan , Jeyakumar Suppandipillai , Sharma Prince , Karaca Mehmet , Jayaraman Kandasamy
Published: November 2024

The computational analysis focuses on the flow performance of a wall-mounted cavity and ramp within DLR scramjet model operating in a reacting flow environment. The analysis encompasses a base setup aligned with DLR experiments, along with suggested configurations featuring different lower wall cavity depth and a fixed upper wall ramp. The 2-D Reynolds-Averaged Navier-Stokes approach (RANS) combined with Shear Stress Transport (SST) k-ω turbulence model, which incorporates single-step reaction chemistry, is utilized in steady-flow simulations. Subsequently, the unsteady-flow computations are completed using the Delayed Detached Eddy Simulation (DDES) with the SST k-ω turbulence model as a continuation of RANS analysis to compute and observe the coherent structures by using data driven methods. To examine shock structures and their associations with shear layer mixing characteristics, the cavity and ramp are positioned downstream of the strut. Inclusion of the cavity and ramp increase the number of shock waves in the flow substantially. Accordingly, complete combustion occur earlier than in the baseline model which is accompanied by a subtle increase in total pressure loss. Due to intense interactions between shock waves and shear layers, combustion zone widens laterally as the cavity displaces the shock train downstream of the strut injector. DDES results are processed to observe the dynamics and the coherent structures employing Dynamic Mode Decomposition (DMD) and Spectral Proper Orthogonal Decomposition (SPOD) methods. Both analysis show that the recirculation zone proceeds into the core engine with the progressive deepening of the cavity leading to a consequential stationary combustion.
Toxic tours and coastal contestation: a photo-essay of the local politics of desalination in California
Authors: O’Neill Brian F
Published: November 2024

Based on visual ethnographic research conducted in a California city from 2019 to 2022, this photo essay elaborates the politics of coastal desalination, the industrial practice of producing drinking water from saline sources. The images provoke a dialogue about how photography can be used, not only as an ethnographic passport, but also in a broader sense of encountering spaces, processes and organizations, thus assisting in unpacking various layers of society and how it (dis)connects with nature. Developing a ‘go-along’ ethnographic approach, such as taking ‘toxic tours’ with research subjects, the techniques of portraiture, landscape and documentary photography were used to produce a sequence of vignettes (as opposed to photographic series) that reveal interlocking modalities of contestation and questions of environmental (in)justices. The combination of images and text uniquely afforded by the format of the photo-essay engenders an understanding not only of the unique individual stories of the people embroiled in this coastal problem, but their connection to wider social structures amidst a seemingly ‘local’ siting struggle.
Optical crack detection and assessment using cholesteric liquid crystal elastomers
Authors: Čamo Tarik , Kizhakidathazhath Rijeesh , Waldmann-Diederich Danièle , Lagerwall Jan PF
Published: November 2024

As one cannot know in advance where a crack will form, currently used discrete crack monitors may miss to detect a crack if it grows outside the monitored regions. A high-resolution continuous 2D strain monitor applied to the entire surface of interest would solve this problem. Cholesteric liquid crystal elastomers (CLCEs) provide this ability, and with recent advances in chemistry, they can be applied very easily, similar to a paint coating. Here we demonstrate the detection of new cracks and monitoring of their progression using CLCE coatings applied to an extruded polystyrene insulation panel, an aerated concrete brick, and a reinforced concrete beam, respectively. Regardless of where and in which direction a crack develops, it can be easily detected thanks to a change in color. By analyzing the new color, quantitative information on the crack width can be extracted. Considering the ease of applying the CLCEs to standard building materials, the high 2D resolution strain monitoring with clear optical detection that it provides, and the low cost of the solution, we argue that CLCE coatings can have a revolutionary impact on structural health monitoring for buildings and infrastructure, to be constructed or already existing.
Closing the Emergent Bilingual Achievement Gaps: A South Texas Culturally Responsive School Principals’ Data-Driven Decision-Making and Instructional Interventions
Authors: Viloria Maria de Lourdes , Gallardo Cynthia , Lozano Ricardo , de la Garza Lina
Published: November 2024

This study focuses on the culturally responsive leadership practices of a South Texas school principal. Texas ranks second out of 10 states with the highest emergent bilingual enrollment. Culturally responsive leadership integrates a dynamic view of the socio-political and cultural contexts in a school setting. As the student population becomes increasingly heterogeneous in Texas classrooms, scholars highlight disparities in academic outcomes across various racial, ethnic, and language groups and argue that paradigmatic shifts are needed to effectively serve minoritized students’ unique educational needs. Accordingly, there is an urgency for principals to be culturally responsive instructional leaders who promote and implement the academic mission of the school via the creation of culturally responsive sustainable instructional practices.
State-of-the-Art Review of Aortic Root Reconstruction: Contemporary Techniques and Challenges
Authors: Elbatarny Malak , White Abby , Chung Jennifer C. Y. , Chauvette Vincent , Guo Ming , Boodhwani Munir , Bozso Sabin , Aboelnazar Nader S. , Dagenais Francois , Laurin Charles , Deng Mimi , Peterson Mark D. , Valdis Matthew , Chu Michael W. A.
Published: November 2024

Aortic root reconstruction operations have undergone substantial evolution with technical modifications, expanding indications, and the need for increasingly complex decision-making. The purpose of this state-of-the-art review is to detail our approach to contemporary aortic root reconstruction operations. First, we review the evolution of root reconstruction procedures over the years and discuss the approach to the aortic root patient for lifetime management of aneurysm and valvular disease in the modern context of management options. We also discuss state-of-the art technical considerations of valve-sparing root replacement, variations of the Ross operation, aortic valve repair principles and challenges in special populations, and considerations for complication-free coronary button reconstruction. We also discuss root reconstruction in high-risk subpopulations including acute type A aortic dissection, congenital, and reoperative patients. We briefly highlight future directions in transcatheter root replacement as well as the outlook for the next generation of aortic root surgeons.
Leveraging intellectual capital and knowledge management to drive innovation and organizational performance
Authors: Suparwadi  , Musadieq Mochammad Al , Riza Muhammad Faisal , Hutahayan Benny
Published: November 2024

In the evolving landscape of higher education, identifying key drivers of organizational performance is crucial. This study investigates the impact of intellectual capital on knowledge management and innovation and how these factors collectively enhance organizational performance. Conducted among top leaders at 21 state universities in Indonesia, this quantitative research used structured questionnaires validated by prior studies. The high response rate strengthens the reliability of findings analyzed using SPSS for descriptive statistics and Structural Equation Modeling (SEM) with SmartPLS 3.0 for hypothesis testing. The results indicate intellectual capital significantly influences knowledge management and innovation, which in turn positively affect organizational performance. Intellectual capital enhances both knowledge management and organizational performance, while effective knowledge management fosters innovation, further contributing to improved performance. The novelty of this research lies in its comprehensive integration of intellectual capital, knowledge management, and innovation within the context of higher education, providing empirical evidence of their interconnectedness and collective impact on organizational performance, which has been largely unexplored in previous studies. This study’s practical implications encourage strategic investments in intellectual capital and knowledge management, ultimately contributing to improved organizational performance and providing valuable insights for policy and decision-making in the higher education sector.
Unveiling a de novo SYNGAP1 variant: Clinical progression and management challenges in a case of developmental and epileptic encephalopathy – A case report
Authors: de León Ojeda Norma E , Villalpando-Vargas Fridha V , Mortola Fabrizio A , Barrera de Leon Juan C , Sánchez-Murguía Tania P , Cisneros-Orozco Jonathan A , Guerrero-Aranda Alioth
Published: November 2024

Developmental and epileptic encephalopathies (DEEs), such as SYNGAP1-related DEE, are marked by severe developmental delays and pharmaco-resistant seizures due to specific genetic variants. This case report focuses on a 9-year-old male with a de novo SYNGAP1 variant (c.1267del, p.Tyr423Metfs*17), illustrating the diagnostic and treatment challenges. Initially experiencing developmental delays and later, misdiagnosed tics, he was diagnosed with epilepsy with eyelid myoclonia at seven. His case includes key SYNGAP1 encephalopathy symptoms: intellectual disability, behavioral issues, and generalized epilepsy resistant to antiseizure medication. The identification of a specific variant adds to our knowledge, suggesting the necessity of considering SYNGAP1-related DEE for unexplained neurodevelopmental delays and seizures. This case underlines the need for a personalized treatment approach focusing on quality of life and symptom management, advancing our understanding and treatment practices for genetic developmental and epileptic encephalopathy.
Spontaneous umbilical cord entwinement in 1-day-old kittens
Authors: Glavinić Aida , Spahija Nermina , Kučlar Muftić Soraja , Šunje-Rizvan Amila , Čengić Benjamin , Mutevelić Tarik , Maksimović Alan
Published: November 2024

Case summary

A 1-year-old domestic shorthair queen with five neonates was referred for umbilical cord entwinement in three kittens 24 h after parturition. The owner noticed the kittens were stuck to each other 3 h before admission. Despite a conservative treatment approach, prolonged ischaemia led to dry gangrenous changes in one of the kitten’s metatarsi.

Relevance and novel information

This and other neonatal complications in cats are rarely reported. Primiparity is a known factor contributing to postpartum complications. Furthermore, inexperienced owners require more assistance in mitigating these challenges. Therefore, further research and collaboration among breeders, owners and veterinary professionals are imperative in order to accurately determine the prevalence of this condition in kittens and develop effective strategies to address it.
A national data sharing solution for the prevention and treatment of obesity—a qualitative study of stakeholders’ needs
Authors: Christenson Anne , Hemmingsson Joanna Uddén , Lagerros Ylva Trolle
Published: November 2024

Study objectives

Obesity-related health data is needed for studies and precision medicine, but existing registers, medical chart systems, and digital platforms are seldom compatible. Before creating improved ways of sharing health data, this study aimed to gather opinions, experiences, and wishes from stakeholders that may use obesity-related health data: healthcare, researchers, people with overweight or obesity, the pharmaceutical industry, and IT-specialists.

Methods

We performed semistructured interviews with 28 stakeholders and analyzed qualitative text data with inductive content analysis. We grouped the suggested parameters in categories.

Results

Time efficient data entering was perceived crucial. Access to health data was important to all participants. Some parameters, such as age, BMI, and sex were requested by all stakeholders. Other data were stakeholder specific, such as population-specific laboratory references, suggested by healthcare professionals only. For people with overweight or obesity, ability to share data with healthcare staff about fitness level or previous weight loss attempts, was important.

Conclusion

The results from this study can be used in the design and implementation of a national health data sharing solution that may be used for precision healthcare use and to evaluate and guide obesity treatment and preventive measures. Data parameters requested by all populations, such as BMI, sex, and age, should be prioritized when designing a data solution. Ability for individuals with overweight or obesity to share health data, may improve healthcare appointments and reduce weight stigma.
Health information-seeking behavior among people living with the two common chronic diseases in low and middle-income countries (LMICs). A systematic review and meta-analysis
Authors: Tesfa Getanew Aschalew , Demeke Abel Desalegn , Zewold Mesafint , Ngusie Habtamu Setegn
Published: November 2024

Objective

The main aim of this review was to systematically collect and summarize the available evidence on health information-seeking behavior among people living with the two common types of chronic diseases in LMICs.

Methods

For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, Google Scholar, and forward and backward citations from included studies. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) procedure were followed to develop and report the review. The pooled effect size and the effect's 95% confidence interval were calculated using a random-effect model meta-analysis for each research. A sub-group analysis was done to investigate potential sources of heterogeneity. To identify publication bias, Egger-weighted regression tests were employed.

Results

A total of 4281 articles were retrieved, with ten studies meeting the eligibility criteria for qualitative synthesis and only seven studies were eligible for the meta-analysis. The pooled extent of health information-seeking behavior among chronic disease patients was 50.5% (95% CI: 35.36–65.70, p = 0.00), with high heterogeneity (I2 = 98.25). Based on the sub-group analysis, it was found that 55% (95% CI: 29.9–79.4) of cancer patients and 40% (95% CI: 36.9%–43.9%) of DM patients sought out health-related information. In studies conducted before 2015, the level of health information seeking was 49%, increasing to 52% (95% CI: 41.0%–62.2%) after 2015.

Conclusion

The overall health information seeking behavior among diabetes and cancer patients has increased over time, but remains relatively low, with only nearly half actively seeking information. The findings also emphasize that patients require health-related information on various topics.. Health educators and health professionals should consider this diversity when developing interventions and educational materials to provide patients with the most comprehensive information and education regarding their healthcare issues.

Protocol registration number

CRD42023433169.
Adulthood Meaning for Spanish Emerging Adults: A Thematic Analysis
Authors: Serrano Cecilia , López-Madrigal Claudia , García-Manglano Javier
Published: November 2024

Previous research on the meaning of adulthood among youth has focused on the move from traditional markers towards individualistic criteria for adulthood. We interview 30 young adults in Spain to investigate how they see adulthood. From our thematic analysis, we extract three major themes (and 16 subthemes): socio-demographic markers (residential independence, age, occupation, family), societal expectations (independence, duties, on your own, nontriviality, other-orientation), and personal resources (autonomy, purpose, thoughtfulness, resilience, realism, responsibility, relational maturity). Our results show that some emerging adults still consider traditional markers of adulthood. A wide range of sub-themes relate to societal expectations, which young people refer to somewhat negatively. In a context in which young people mostly see adulthood with an individualistic lens, two sub-themes emerge which make references to others –being other-oriented and able to establish mature relationships; even if quantitatively these were not as frequent as other sub-themes, we find these deserve further attention.
Theorizing the spatiality of ICT-mediated transnational repression: Evidence from China’s repression of Uyghurs in Turkiye
Authors: Oztig Lacin Idil , Karluk Abdurresit Celil
Published: November 2024

Recent years have witnessed burgeoning scholarly interest in how authoritarian states use transnational repression to intimidate and punish their citizens abroad. Our freshly collected surveys and in-depth interviews with members of the Uyghur diaspora in Turkiye reveal that China’s transnational repression of the Uyghur diaspora goes beyond preventing political mobilization. With the use of Internet Communication Technologies (ICTs), China employs widespread repression against ordinary Uyghurs by cutting off their communication lines with their homeland and through the Chinese police constantly harassing and threatening them, mostly through social media applications. Despite the growing body of literature on transnational repression, the spatial dimension of ICT-mediated transnational repression remains relatively undertheorized. Building on the literature of critical geopolitics, digital geographies, and Foucault’s concept of panopticon this study theorizes that China’s ICT-based practices beyond its borders have led to the configuration of “a transnational social space of insecurity,” which constitutes an idiosyncratic form of repression and spatiality by affecting diaspora Uyghurs’ everyday practices through the pervasive use of tech-based apparatuses and mechanisms. This idiosyncratic space constitutes and is constituted by “disciplinary” and “automated” subjects pushed toward constant self-surveillance and self-discipline. While China has physically turned East Turkestan into an open prison through political education camps, forced labor in production chains, ubiquitous installation of CCTV cameras, and frequent police control on phones and computers, ICTs enable China to transfuse its repressive system to the transnational domain by creating a parallel social space, which functions as its quasi-spatial extension.
Little legacies: Another creativity benefit for older adults
Authors: Zheng Mei , Kaufman James C.
Published: November 2024

Adams-Price and Morse offer a wonderfully comprehensive overview of the benefits of creativity for older adults. In this commentary, we expand on a topic they briefly mention: the idea of leaving a creative legacy. We briefly explore research on meaning in older adults, then discuss Rank and Lifton’s ideas about symbolic immortality and the desire to leave behind a legacy. Creative works are on pathway, but we emphasize that it is not only Big-C contributions that qualify. Mini-c and little-c creativity can leave meaningful legacies for family, friends, and one’s community.
Traversing the climate deadlock: Embracing the idea of communism
Authors: Swyngedouw Erik
Published: November 2024

Despite widely shared consensus about the truth of climate change and a plethora of activities, the climate high-speed train keeps thundering forward with very little hope for a serious inflection of the history of the future. It is this deadlock, that is, the gap between knowing and acting, that requires traversing if an effective and equitable socio-ecological transition is to be inaugurated. In this contribution, we contend that the idea of communism offers an opening through which the present climate deadlock can be politicized. Mobilizing a Lacanian psychoanalytic perspective, the paper accounts for the ‘fetishic disavowal’ that sutures much of climate discourse and action. Traversing the climate deadlock and the disavowal of its underlying dynamics requires engaging with the Idea of Communism as a political imaginary for a climate-sensible and socially equitable world to be made. This idea is still a potent and possibly necessary one.
Carbon markets have no future in a (net) zero-emissions world
Authors: Grubert Emily
Published: November 2024

This commentary explains why market signals are insufficient to support a zero greenhouse gas emissions outcome: markets function by sorting based on cost and/or profitability, and there is nothing to sort when the target is zero. It then describes why sorting is ineffective even on the path to zero emissions, given that the most societally critical emissions (i.e. those that should be allowed to continue the longest) are not necessarily the most financially costly to eliminate. This observation also means that even for a net-zero emissions target, where some emissions do continue, markets are unlikely to identify the most societally preferred emissions to preserve without an exogenous declaration of preference, and could distort the development of potentially critical industrial functions along the way. Finally, the commentary concludes with an alternative proposal, for a centrally coordinated transition towards a known end goal – a major difference from settings where markets perform well.
Identifying persistent high-cost patients in the hospital for care management: development and validation of prediction models
Authors: de Ruijter Ursula W. , Kaplan Z. L. Rana , Eijkenaar Frank , Maas Carolien C. H. M. , van der Heide Agnes , Bax Willem A. , Lingsma Hester F.
Published: November 2024

Background

Healthcare use by High-Need High-Cost (HNHC) patients is believed to be modifiable through better coordination of care. To identify patients for care management, a hybrid approach is recommended that combines clinical assessment of need with model-based prediction of cost. Models that predict high healthcare costs persisting over time are relevant but scarce. We aimed to develop and validate two models predicting Persistent High-Cost (PHC) status upon hospital outpatient visit and hospital admission, respectively.

Methods

We performed a retrospective cohort study using claims data from a national health insurer in the Netherlands—a regulated competitive health care system with universal coverage. We created two populations of adults based on their index event in 2016: a first hospital outpatient visit (i.e., outpatient population) or hospital admission (i.e., hospital admission population). Both were divided in a development (January-June) and validation (July-December) cohort. Our outcome of interest, PHC status, was defined as belonging to the top 10% of total annual healthcare costs for three consecutive years after the index event. Predictors were predefined based on an earlier systematic review and collected in the year prior to the index event. Predictor effects were quantified through logistic multivariable regression analysis. To increase usability, we also developed smaller models containing the lowest number of predictors while maintaining comparable performance. This was based on relative predictor importance (Wald χ2). Model performance was evaluated by means of discrimination (C-statistic) and calibration (plots).

Results

In the outpatient development cohort (n = 135,558), 2.2% of patients (n = 3,016) was PHC. In the hospital admission development cohort (n = 24,805), this was 5.8% (n = 1,451). Both full models included 27 predictors, while their smaller counterparts had 10 (outpatient model) and 11 predictors (hospital admission model). In the outpatient validation cohort (n = 84,009) and hospital admission validation cohort (n = 20,768), discrimination was good for full models (C-statistics 0.75; 0.74) and smaller models (C-statistics 0.70; 0.73), while calibration plots indicated that models were well-calibrated.

Conclusions

We developed and validated two models predicting PHC status that demonstrate good discrimination and calibration. Both models are suitable for integration into electronic health records to aid a hybrid case-finding strategy for HNHC care management.
An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a German healthcare payer perspective
Authors: Kuniss Malte , Hillcoat Lucy , Moss Joe , Straube Florian , Andrade Jason , Wazni Oussama , Chierchia Gian Battista , Schwegmann Lukas , Ismyrloglou Eleni , Sale Alicia , Mealing Stuart , Bromilow Tom , Lane Emily , Lewis Damian , Goette Andreas
Published: November 2024

Background

Three recent randomized controlled trials demonstrated that, in patients with symptomatic paroxysmal atrial fibrillation (PAF), first-line pulmonary vein isolation with cryoballoon catheter ablation reduces atrial arrhythmia recurrence compared to initial antiarrhythmic drug (AAD) therapy. This study aimed to evaluate the cost-effectiveness of first-line cryoablation compared to first-line AADs from a German healthcare payer perspective.

Methods

Individual patient-level data from 703 participants with untreated PAF enrolled into three randomized clinical trials (Cryo-FIRST, STOP AF First and EARLY-AF) were used to derive parameters for the cost-effectiveness model (CEM).

The CEM structure consisted of a hybrid decision tree and Markov model. The decision tree (one-year time horizon) informed initial health state allocation in the first cycle of the Markov model (40-year time horizon; three-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Cost inputs were sourced from German diagnosis-related groups and the Institute for the Hospital Remuneration System (InEK). Costs and benefits were discounted at 3% per annum.

Results

Cryoablation was cost-effective, incurring ~ €200 per patient while offering an increase in QALYs (~ 0.18) over a lifetime. This produced an average incremental cost-effectiveness ratio of ~ €1,000 per QALY gained. Individuals were expected to receive ~ 1.2 ablations over a lifetime, regardless of initial treatment. However, those initially treated with cryoablation as opposed to AADs experience 0.9 fewer re-ablations and a 45% reduction in time spent in AF health states.

Conclusion

Initial rhythm control with cryoballoon ablation in symptomatic PAF is a cost-effective treatment option in a German healthcare setting.
Heparan sulfate in cerebrospinal fluid as a biomarker to assess disease severity and for treatment monitoring in patients with Mucopolysaccharidosis Type II: a position statement
Authors: Giugliani Roberto , de Siqueira Ana Cecília Menezes , Santos Emerson Santana , Leão Emília Katiane E. A. , Carvalho Gerson da Silva , Santos Mara Lúcia Schmitz Ferreira , Raskin Salmo , Martins Ana Maria
Published: November 2024

Patients with mucopolysaccharidosis type II (MPS II) can present with a severe neuronopathic phenotype or an attenuated non-neuronopathic phenotype. In the light of the recent development of drugs that cross the blood-brain barrier for treatment of neurologic MPS II symptoms, it is critical to define biomarkers that objectively differentiate phenotypes and monitor therapeutic outcomes of advanced treatments. In December 2023, a panel of Brazilian experts discussed the potential of quantifying heparan sulfate (HS) in the cerebrospinal fluid (CSF) as a biomarker for assessing neurological impairment in patients with MPS II, as well as the potential of the molecule as an objective parameter for therapeutic monitoring. Based on scientific evidence, the experts concluded that HS in CSF is predominantly derived from the brain and reflects neurological impairment in patients with MPS II. CSF HS levels may help differentiate between neuronopathic and non-neuronopathic forms of MPS II, with preliminary observations suggesting a potential threshold around 4,000 ng/mL when HS quantification is performed using the same method described in clinical studies of pabinafusp alfa. According to the authors, monitoring HS levels in CSF can serve as an objective parameter for assessing the effectiveness of treatment with drugs that cross the blood-brain barrier. The recommended timing of HS evaluations in CSF of patients with the severe phenotype is: (i) before treatment; (ii) six months after starting treatment; and (iii) two years after starting treatment. The same monitoring scheme is recommended for patients with the attenuated MPS II phenotype, however, after two years of treatment, the physician may elect to perform regular neurocognitive evaluations instead of measuring HS in CSF. Lastly, the authors reinforced the importance of evaluating adherence to treatment, including interruptions, to provide a more meaningful assessment of the treatment’s real-world impact and to determine the ideal timing of CSF collection for therapeutic monitoring.
YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway
Authors: Dai Bao , Xu Lei , Rong Shikuo , Song Muye , Lan Ziteng , Chen Weijian , Zhang Lingyun , Liu Yongchen , Wang Linhe , Li Jinghua , Chen Jian , Wu Zeyu
Published: November 2024

Background

RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of the m6A reader YTH domain family 2 (YTHDF2) has not been reported in anaplastic thyroid cancer (ATC) and its biological mechanism is unclear.

Methods

The relationship between YTHDF2 expression and ATC was determined using data sets and tissue samples. A range of analytical techniques were employed to investigate the regulatory mechanism of YTHDF2 in ATC, including bioinformatics analysis, m6A dot-blot analysis, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, RNA sequencing, RNA stability assays and dual luciferase reporter gene assays. In vitro and in vivo assays were also conducted to determine the contribution of YTHDF2 to ATC development.

Results

YTHDF2 expression was significantly increased in ATC. The comprehensive in vitro and in vivo experiments demonstrated that YTHDF2 knockdown significantly attenuated ATC proliferation, invasion, migration, and apoptosis promotion, whereas YTHDF2 overexpression yielded the opposite trend. Mechanistically, RNA-seq, MeRIP-seq and RIP-seq analysis, and molecular biology experiments demonstrated that YTHDF2 accelerated the degradation of DNA damage-inducible transcript 4 or regulated in DNA damage and development 1 (DDIT4, or REDD1) mRNA in an m6A-dependent manner, which in turn activated the AKT/mTOR signaling pathway and induced activation of epithelial-mesenchymal transition (EMT), thereby promoting ATC tumor progression.

Conclusions

This study is the first to demonstrate that elevated YTHDF2 expression levels suppress DDIT4 expression in an m6A-dependent manner and activate the AKT/mTOR signaling pathway, thereby promoting ATC progression. YTHDF2 plays a pivotal role in ATC progression, and it may serve as a promising therapeutic target in the future.
Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study
Authors: Trippler Lydia , Ali Said Mohammed , Masoud Msanif Othman , Mohammed Zahor Hamad , Amour Amour Khamis , Suleiman Khamis Rashid , Ame Shaali Makame , Kabole Fatma , Hattendorf Jan , Knopp Stefanie
Published: November 2024

Background

The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis.

Methods

During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted.

Results

Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1–0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence.

Conclusions

The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance.

Trial registration: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493

Graphical Abstract
Analysis of spatial filtering in neural spatiospectral filters and its dependence on training target characteristics
Authors: Briegleb Annika , Kellermann Walter
Published: November 2024

Mask-based multichannel speech enhancement methods based on artificial neural networks estimate a mask that is applied to the multichannel input signal or a reference channel to obtain the estimated desired signal. For the estimation, both spectral and spatial cues from the multichannel input can be used. However, the interplay of the two inside the neural network is typically unknown. In this contribution, we propose a framework to analyze neural spatiospectral filters (NSSFs) with respect to their capabilities to extract and represent spatial information. We explicitly take the characteristics of the training target signal into account and analyze its effect on the functionality of the NSSF. Using two conceptually different NSSFs as example, we show that not all NSSFs use spatial information under all circumstances and that the training target signal has a significant influence on the spatial filtering behavior of an NSSF. These insights help to assess the signal processing capabilities of neural networks and allow to make informed decisions when configuring, training, and deploying NSSFs.
Numerical Response of Concrete-Filled Steel Tubular (CFST) Columns Externally Strengthened with FRP Composites Subjected to Cyclic Loading
Authors: Mansour Walid , Osama Bothaina , Li Weiwen , Wang Peng , Sobuz Md. Habibur Rahman
Published: November 2024

The ultimate load-carrying capacity of concrete-filled steel tubular (CFST) columns exposed to monotonic loadings can be greatly increased by strengthening those columns, and the occurrence of the steel tube's outward buckling can be postponed. The current research aims to study the possibility of improving the structural characteristics of CFST columns exposed to cyclic loadings in terms of lateral load capacity and absorbed energy by strengthening them with different patterns of fiber-reinforced polymer (FRP) sheets. The ABAQUS software was used to create a three-dimensional (3D) non-linear finite element model (FEM) to simulate the behavior of FRP-strengthened CFST columns exposed to monotonic and cyclic loadings. After ascertaining the accuracy of the proposed model's results in successfully predicting failure patterns and lateral loads compared to the experimental results of tested specimens available in the literature, the model was used to create a parametric study. The parametric study focused on the impacts of the thickness, location, and length of the strengthening sheets on the failure pattern, lateral load-carrying capacity, stiffness, cumulative energy, absorbed energy, and viscous damping factor of the CFST columns exposed to cyclic loadings. The results revealed that the un-strengthened specimen displayed a maximum lateral load of 185 kN and a viscous damping factor of 45.2% at a lateral drift of 5.7%. On the other hand, strengthening the CFST column using five layers of FRP sheets exhibited the highest lateral load of all investigated columns (50% more than the un-strengthened specimen). Additionally, at a lateral drift of 5.7%, the decrease in viscous damping factor of CFST specimens due to strengthening using 1, 2, 3, 4, and 5 layers of FRP sheets with respect to the control specimen was 7.9%, 14.9%, 20.8%, 27.7%, and 30.3%, respectively.
Satellite telemetry reveals complex mixed movement strategies in ibis and spoonbills of Australia: implications for water and wetland management
Authors: McGinness Heather M. , Lloyd-Jones Luke R. , Robinson Freya , Langston Art , O’Neill Louis G. , Rapley Shoshana , Jackson Micha V. , Hodgson Jessica , Piper Melissa , Davies Micah , Martin John M. , Kingsford Richard , Brandis Kate , Doerr Veronica , Mac Nally Ralph
Published: November 2024

Waterbird population and species diversity maintenance are important outcomes of wetland conservation management, but knowledge gaps regarding waterbird movements affect our ability to understand and predict waterbird responses to management at appropriate scales. Movement tracking using satellite telemetry is now allowing us to fill these knowledge gaps for highly mobile waterbirds at continental scales, including in remote areas for which data have been historically difficult to acquire. We used GPS satellite telemetry to track the movements of 122 individuals of three species of ibis and spoonbills (Threskiornithidae) in Australia from 2016 to 2023. We analysed movement distances, residency periods and areas, and foraging-site fidelity. From this we derived implications for water and wetland management for waterbird conservation. This is the first multi-year movement tracking data for ibis and spoonbills in Australia, with some individuals tracked continuously for more than five years including from natal site to first breeding attempt. Tracking revealed both inter- and intra-specific variability in movement strategies, including residency, nomadism, and migration, with individuals switching between these behaviours. During periods of residency, areas used and distances travelled to forage were highly variable and differed significantly between species. Sixty-five percent of identified residency areas were not associated with wetlands formally listed nationally or internationally as important. Tracking the movements of waterbirds provides context for coordinated allocation of management resources, such as provision of environmental water at appropriate places and times for maximum conservation benefit. This study highlights the geographic scales over which these birds function and shows how variable waterbird movements are. This illustrates the need to consider the full life cycle of these birds when making management decisions and evaluating management impacts. Increased knowledge of the spatio-temporal interactions of waterbirds with their resource needs over complete life cycles will continue to be essential for informing management aimed at increasing waterbird numbers and maintaining long-term diversity.