bluuebunny/crossref_metadata_2025 huggingface dataset:
Cb-WoFS: Migrating the Warn-on-Forecast System to the Cloud
Authors: Martin Joshua J. , Clark Adam J. , Yussouf Nusrat , Wicker Louis , Heinselman Pamela , Knopfmeier Kent , Matilla Brian C. , Burke Patrick C. , Adili Salar
Published: September 2024

This article provides a brief, technical narrative of the WoFS journey to a cloud-based high-performance computing (HPC) system, including some of the technological challenges encountered and solutions found. Also, discussed are a few new components that are in development for cloud-based Warn-on-Forecast System (cb-WoFS), such as the cloud infrastructure project for managing resources, as well as a new web application that manages cb-WoFS runs. An important initial step in our cloud journey is containerizing all of the compiled applications, such as WRF, GSI, and EnKF and their dependencies like netCDF and MPI. With these applications compiled within an Apptainer container, WoFS can run on any local or cloud-based HPC cluster that supports MPI. Furthermore, an additional software layer was developed that creates and manages cloud vendor resources. This layer, which is referred to as the WoFS framework, contains the workflow required to run cb-WoFS, as well as management for other aspects of cb-WoFS (including but not limited to creation of HPC pools in the end-to-end workflow, runtime notifications, and database management). This additional layer was developed to separate the WoFS business logic from vendor-specific API calls. The WoFS framework exposes features through its service library, which is then referenced by the newly developed cb-WoFS web application and other cloud applications. This makes WoFS a complete end-to-end cloud-based application, where an administrator can launch a model run, manage resources, and view output all within a single web app.
Impacts of the Madden–Julian Oscillation on the Flash Drought Occurrence over the Lancang–Mekong River Basin
Authors: Chen Guiwan , Ling Jian , Lin Zhaohui , Xiao Ziniu , Li Chongyin
Published: September 2024

This study explores the potential impacts of the Madden–Julian oscillation (MJO) on flash drought occurrence over the Lancang–Mekong River basin (LMRB). The flash drought events are identified across individual grid cells from gridded datasets, based on the rapid decline rate in soil moisture and dry persistency of flash droughts. The onset of flash drought is typically accompanied by precipitation deficit and abnormal increase in surface air temperature (SAT). Both the onset and persistency risks of flash drought vary significantly depending on the MJO phase. Generally, the onset and persistency risks of flash droughts over the LMRB increase when the MJO convection is active over the Indian Ocean (phases 2–3), while decrease when the MJO is active over the Pacific Ocean (phases 6–7). The MJO primarily influences flash droughts over the lower reaches of the LMRB by modulating SAT and precipitation. During MJO phases 2–3, there exists significant increased SAT and preceding precipitation deficit over the lower reaches, leading to decline in soil moisture. During MJO phases 6–7, there are decreased SAT and preceding increased precipitation. Diagnosis results revealed that the impact of the MJO on SAT over the lower reaches is dominated by large-scale temperature advection associated with the MJO-induced vertical and meridional circulation anomalies, while its impact on precipitation is mainly modulated by the MJO-induced zonal wind gradients. This study emphasizes the importance of considering the effects of the MJO on precipitation and SAT for predicting flash droughts over the LMRB.
Establishing Benchmarks for Airway Replacement: Long-Term Outcomes of Tracheal Autografts in a Large Animal Model
Authors: Liu Lumei , Sher Ada C. , Arsuaga-Zorrilla Carmen , Shamim Humra , Nyirjesy Sarah , Shontz Kimberly M. , Hussein Zakarie , Sussman Sarah , Manning Amy , Chiang Tendy
Published: September 2024

Objective:

Airway replacement is a challenging surgical intervention and remains an unmet clinical need. Due to the risk of airway stenosis, anastomotic separation, poor vascularization, and necrosis, it is necessary to establish the gold-standard outcomes of tracheal replacement. In this study, we use a large animal autograft model to assess long-term outcomes following tracheal replacement.

Methods:

Four New Zealand White rabbits underwent tracheal autograft surgery and were observed for 6 months. Clinical and radiographic surveillance were recorded, and grafts were analyzed histologically and radiographically at endpoint.

Results:

All animals survived to the endpoint with minimal respiratory symptoms and normal growth rates. No complications were observed. Computed tomography scans of the post-surgical airway demonstrated graft patency at all time points. Histological sections showed no sign of stenosis or necrosis with preservation of the native structure of the trachea.

Conclusion:

We established benchmarks for airway replacement. Our findings suggest that a rabbit model of tracheal autograft with direct reimplantation is feasible and does not result in graft stenosis or airway collapse.
The association between neighborhood socioeconomic deprivation and mental health in low- and middle-income countries: A scoping review
Authors: Sharifi Vandad , Amini Homayoun , Radman Narges , Noorbakhsh Hoora , McClurg Caitlin , Patten Scott B
Published: September 2024

Background:

Environmental research on mental health primarily originates from high-income countries, while information about the rest of the world remains limited.

Aims:

This study examined: (1) the available published research evidence regarding the association between neighborhood-level deprivation and indicators of mental health and illness in low- and middle-income countries (LMICs), and (2) the gaps in the relevant research in LMIC settings that should be addressed in future studies.

Method:

First, we systematically searched for relevant primary studies in electronic databases (Ovid Medline, Scopus, Socindex, and PsycINFO) and citations in the reference lists. Then, a two-stage screening procedure was employed to select the relevant studies by screening the titles and abstracts and reviewing the selected full texts by independent researchers. After charting the data from the selected study reports, we collated, summarized, and discussed the results.

Results:

We retrieved 51 studies across 19 LMICs, with only one study originating from a low-income country. Most studies focused on adult mental health topics and few explored children’s mental health. Notably, a significant majority of these studies ( N = 37) reported a positive association between neighborhood deprivation and mental health/disorder. However, the research methods used varied significantly, and there were several methodological limitations.

Conclusions:

This review highlights the need for more original studies in LMICs on the association between neighborhood deprivation and mental health, employing stronger methodologies.
Between Communism and Nationalism: Slovene Communist Spatial Politics in the North Adriatic Region, 1943–54
Authors: Batič Matic
Published: September 2024

The article deals with the spatial policies of the Slovene communist authorities in the border area of the North Adriatic between 1943 and 1954. At that time, this territory was claimed by several state entities with different ideological and political systems. All of them sought to establish their sovereignty over the region not only politically and militarily but also culturally. Those endeavours included processes of ideologically charged transformation of public space. This also applies to the Slovene communists, whose spatial policies were characterized by a mixture of nationalist and communist impulses. Although the communist authorities agreed in principle to the idea of internationalism, their interventions actually led to spatial Slovenization. At the same time, the communist dimension manifested itself in the negative attitudes towards buildings associated with ideological enemies of communism, especially the Catholic Church and nobility.
The Effects of Video Presence on Associative and Source Memory Among Younger and Older Adults in a Virtual Social Simulation
Authors: Xiang Angela , Lecompte Mariah , Yang Lixia
Published: September 2024

The current study aimed to examine how video presence in a simulated virtual socialization meeting would affect younger ( n = 60) and older adults’ ( n = 65) associative and source memory. Participants were instructed to watch a simulated virtual meeting where speakers introduced themselves with a name and an occupation, half with their video on and the other half with their video off. Participants completed a recognition test of intact, rearranged, and new name–occupation pairs. For pairs recognized as old, participants were asked to identify whether the pair was presented with their video on or off. The associative memory accuracy (i.e., hit rate – false alarm rate) results showed a better performance in younger relative to older adults, but both age groups benefited equally from video presence. Source memory (i.e., video-on vs. video-off) results showed a significant benefit of video presence in older but not younger adults.
New Breakthroughs in Hindered Amine Light Stabilizer Performance
Authors: Vulic I. , Eng J.M. , Samules S.-B. , Wagner A.H.
Published: September 2024

The role of hindered amine light stabilizers (HALS) in the protection of polyolefins continues to expand. HALS are essential components in formulations developed for outdoor use and have been proven to be effective thermo-oxidative stabilizers. The physicochemical properties of hindered amines have a profound effect on the hindered amine’s performance as a stabilizer, and will also influence the reactivity of the HALS with other formulation components, environmental agents, etc. Some of these interactions can have a deleterious effect on end product aesthetics and service life.

Studies on the relationship between HALS structure and performance have led to the development of new products which provide optimal light stabilizing efficiency while minimizing the tendency to undergo undesirable side reactions with system components or external agents. These new products and their application in PP fibre, PE film, and other applications will be described.
Studies of Acetone-Formaldehyde-m-Aminophenol Resins and their Composite Formation
Authors: Patel Hasmukh S. , Dixit Bharat C. , Dixit Ritu B.
Published: September 2024

An acetone-formaldehyde (AF) resin containing methylol (-CH2OH) groups was prepared and condensed with m-aminophenol (mAP) in the presence of alcoholic alkali catalyst at varying mole ratios of AF:mAP; 1:1, 1:1.5 and 1:2. The resultant AF-mAP resin was characte.,tized by elemental analysis, IR spectral studies, number average molecular weight (M̄n) estimated by non-aqueous conductometric titration and thermogravimetry. The curing reaction between AF-mAP resin and hexamethylenetetramine (HMTA) was monitored by differential scanning calorimetery (DSC) and kinetic parameters were evaluated. Glass-reinforced composites (i.e. laminates) based on the AF-mAP-HMTA system were also prepared and characterized by mechanical properties.
Micromechanical Study of Interface Stresses and Failure in Fibrous Composites Using Boundary Element Method
Authors: Kwon Y. W. , Eren H.
Published: September 2024

Because interface failure has been a common failure mode in reinforced composite materials, the authors investigated the micromechanical interface stress distribution and potential failure in fibrous composite materials under transverse loading, using the boundary element method. Both normal and tangential interface stresses were computed around fibres of different geometrical shapes and volume fractions. In addition, interface stresses around fibres located deep inside of a composite specimen or at the boundary of the specimen were calculated and compared. This study examined the interface failure initiation and growth for various cases as described above. The quadratic failure criterion, based on the interface normal and shear stresses, was considered at the interface to compare the failure under different cases. The effect of progressive interface failure on the composite stiffness was also studied for different cases, as mentioned above.
Using Human-Centered Design to Decrease the Risk of Toileting in Hospitals for Patients and Clinicians
Authors: O’Neill Kate , Doran Molly , Davie Keelin , Andreano Anthony , Tulk Jesso Stephanie
Published: September 2024

Patient falls are common injuries in hospitals, and many occur surrounding a patient’s need to use the bathroom. In this study, we used the TripTech Method to design and evaluate early-stage design concepts for fall prevention and reduction of occupational injury associated with toileting falls. Nurse participants saw an opportunity in getting their patients to engage in their own recovery in increase the potential for cooperation, and also desired tools which could make the process physically easier for staff and patients which were also accessible when needed. Participants also discussed concerns about higher-tech tools, including affordability issues which could lead to further healthcare disparity. Overall, our research demonstrates how human-centered methods are valuable in focusing design efforts on the most pressing challenges experienced by users to avoid wasted investment in ineffective or unwanted technology.
Public Health Decision-Making Using Uncertainty Displays
Authors: Tessema Tselot , Vasquez Holland , Rosella Laura , Donmez Birsen
Published: September 2024

High rates of chronic disease have created challenges for public health decision-makers in resource allocation. Decision tools designed to support public health professionals can help address these challenges. This study aims to investigate the impact of different uncertainty visualization techniques on user perceptions. The study was designed for the purpose of supporting the development of CDPoRT, a chronic disease risk prediction tool. Participants performed a fictional recourse allocation decision-making task with map-based visualizations, tables with and without uncertainty data, and a table with uncertainty explanation. The findings show that CDPoRT’s user interface may benefit from the inclusion of an overlay map to visualize the rate and uncertainty information for public health resource allocation decisions. Future research can consider the development of interactive features to facilitate comparisons between multiple geographical regions and simulate interventions.
Honoring the Ancestors: A Culturally Responsive Response to Intervention Framework for Diverse, Twice-Exceptional Students
Authors: Bianco Margarita , Brandehoff Robin , Castillo-Tristani Yenitza
Published: September 2024

In this article, the authors illustrate how teachers use a strength based, culturally responsive Response to Intervention (RTI) framework to meet the varied needs of a culturally diverse, twice-exceptional student. Using a case-based approach, the authors demonstrate how classroom teachers and specialists collaborate with the student and her family to create an individualized system of supports designed to nurture the student’s gifted potential while simultaneously addressing her cultural needs and learning disabilities. Using a hypothetical case, a student’s curiosity about her Puerto Rican heritage and multiracial identity becomes the central focus as teachers build a thematic unit of instruction that honors her ancestors. As the student learns about her Indigenous Taíno and African heritage, she is taught to use specific evidence-based learning strategies to improve her memory, study skills and build on her curiosity and multilingual strengths. Throughout the article, the authors provide explicit examples of how to create a culturally responsive RTI plan for a diverse twice-exceptional student.
Exact-time neural attitude control for flexible spacecraft with conditional disturbance negation
Authors: Sun Yu , Ma Guangcheng , Wang Guan , Xia Hongwei , Chen Changwen
Published: September 2024

This paper proposes a selectively anti-disturbance control design for low-frequency flexible spacecraft while meeting strict convergence time constraints. Conditional disturbance negation (CDN) is investigated to make maximum use of disturbances by compensating harmful ones selectively while profiting from beneficial ones, which suppresses chattering in variables. Exact-time control (ETC) achieves exact and independent appointment of the convergence time by introducing a regulation function in the predefined-time control with neural networks (NN) removing singularity. ETC combined with CDN guarantees time accuracy and small chattering simultaneously. The globally exact-time stability analysis is conducted rigorously, and the boundedness of all variables can be achieved. Comparative simulations demonstrate the superiority and feasibility of the proposed controller.
“I was Struggling at the Beginning to Even Show People or do it… it was Very Emotional at Moments”: Exploring the Process of Art Creation in an Arts-Informed Research Method Among mothers From Ontario, Canada With Experiences of Gender-Based Violence
Authors: Mantler Tara , Jackson Kimberley T. , Broadbent Madison , Butler Emma , Yates Julia
Published: September 2024

Gender-based violence (GBV), or violence perpetrated against someone based on their gender stemming from gender norms and/or unequal power dynamics, impacts women worldwide. It is well documented that during reproductive years, women face a heightened risk of experiencing GBV; however, the impacts of these experiences remain complex. While some literature points to negative health impacts for both mothers and children following experiences of GBV, other research has revealed that for some women, being a mother serves as a source of strength in addressing violence. More research is needed to address this dichotomy in findings, however, many barriers to research participation exist for this vulnerable population. Arts-informed research, a method underscored by empathy, support, and holding space for participants, has been identified as potential conduit to break down potential barriers. Therefore, the purpose of this qualitative, cross-sectional study was to explore the process of arts creation as an arts-informed research method among mothers with experiences of GBV. Guided by Thorne’s interpretive description, 13 mothers created a visual art form that reflected their experience of mothering in the context of GBV, before, during, and after which participants were encouraged to journal about the experience. Following the art creation, individual, semi-structured interviews were conducted via Zoom to explore the process of art creation and interpretation of the art form. Analysis revealed two distinct but interrelated themes, including: (1) the process of participating in the art creation; and (2) the process of journaling to create. The arts-informed research process afforded new insights, including those that are typically not accessible through traditional qualitative data collection methods. Future research should explore structural factors that exist that enable mothers with experiences of GBV to fully participate and benefit from arts-informed methods.
Leadership, liminality, and ‘wicked’ conflicts: John Hume and the untangling of the Northern Ireland ‘Troubles’
Authors: Murphy Joanne
Published: September 2024

When in 1998, the historic Belfast/Good Friday Agreement marked the end of the 30-year violent Northern Ireland conflict often referred to as the ‘Troubles’, many commentators regarded it as the culmination of the life’s work of one man: John Hume. Hume was seen by many as a man of peace, but for others he was a trojan horse for violent Irish nationalism. This paper explores these contradictions through the lens of liminality and argues that central to Hume’s ability to create change in a schismogentic environment of conflict was his own ‘inbetweenness’: a leader of nationalism, but not a nationalist, a believer in non-violence, who engaged actively with men of violence, an MP elected to a British parliament, who worked hand in hand with the Irish Department of Foreign Affairs. In doing so it proposes a typology of five liminal leadership approaches which allowed for the untangling of the conflict over time: Reframing the Problem; Stakeholder Cultivation; Opening Linguistic Space; Practicing Disruption; and Acceptance of Sacrifice. This paper makes three contributions: to our understanding of leaders who inhabit and utilise liminal spaces, to leadership approaches in zero sum environments including those riven by ‘wicked’ conflicts, and to an understanding of Hume himself and his legacy.
Artificial intelligence – the emperor's new clothes?
Authors: Hofmann Bjørn
Published: September 2024

There is a massive hype of artificial intelligence (AI) allegedly revolutionizing medicine. However, algorithms have been at the core of medicine for centuries and have been implemented in technologies such as computed tomography and magnetic resonance imaging machines for decades. They have given decision support in electrocardiogram machines without much attention. So, what is new with AI? To withstand the massive hype of AI, we should learn from the little child in H.C. Andersen's fairytale “The emperor's new clothes” revealing the collective figment of the emperor having new clothes. While AI certainly accelerates algorithmic medicine, we must learn from history and avoid implementing AI because it allegedly is new – we must implement it because we can demonstrate that it is useful.
Exploring the Link Between Teachers’ Motivation for Continuous Professional Development and Professional Learning Communities: A Structural Equation Modeling Approach
Authors: Belay Sintayehu , Melesse Tadesse
Published: September 2024

This study’s main objective was to use structural equation modeling to examine the direct effects of teachers’ amotivation, identified regulation, external regulation, introjected regulation, and intrinsic motivation on PLC development in Ethiopia’s Awi administrative zone’s primary and middle schools. For this purpose, a correlational quantitative study design was used. The arbitrarily selected 342 primary and middle school teachers were the major data sources through a questionnaire. The findings of this study confirmed that unlike identified regulation, introjected regulation, and amotivation, teachers’ intrinsic motivation for continuous professional development and external regulation has a significantly positive and strong direct effect on building a professional learning community in schools. Besides, teacher intrinsic motivation fully mediated the influence of introjected regulation and identified regulation on enhancing professional learning communities, but amotivation and external regulation did not. In conclusion, the study underscores the critical role of intrinsic motivation in fostering PLC development in schools. Educational stakeholders should prioritize initiatives that promote teachers’ intrinsic motivation, autonomy, and sense of purpose to cultivate vibrant learning communities.
Impact of a Structured Roadmap, Individual Accountability and Support, and Outcome Measurement on the Culture of Scholarship in a Residency Program
Authors: Waheed Abdul , Azhar Erum , Aziz Faisal , Nasir Munima , Chaudhary Muhammad Ali , Wang Li
Published: September 2024

BACKGROUND

Despite scholarly activity being an accreditation requirement for residency programs by the Accreditation Council for Graduate Medical Education (ACGME) since 2006, many family medicine programs have struggled to meet this requirement. A myriad of approaches and curricula have been proposed to enhance the scholarly output of residency programs.

OBJECTIVES

To determine the impact of a multimodal curricular intervention consisting of clear expectations, structured roadmap, availability of resources, and standardized accountability on the scholarly activity of residents.

METHODS

This is a quasi-experimental study with a retrospective data collection. The scholarly activities of residents completing training in the pre-intervention (2009-2012) and post-intervention period (2013-2017) were compared. Chi-square, Fisher's exact, Mann Whitney U, and Kruskal Wallis H tests were utilized to detect differences between the pre- and post-intervention groups. Multivariable Poisson regression models were used to detect independent predictors of per-resident scholarly activity. The institutional review board determined that the study was exempt from full review.

RESULTS

A total of 67 residents, 20 (30%) pre-intervention and 47 (70%) post-intervention, were included in the analysis. The number of total scholarly activities per resident increased significantly in the post-intervention period after adjusting for confounding factors (1.9 vs 6.4). The number of scholarly activities per resident also showed an increasing trend over time ( P = .04). Moreover, traditional scholarship, including published manuscripts (0.35 vs 2.43) and national-level presentations (0.35 vs 1.27) also increased in the post-intervention period.

CONCLUSION

Implementing this comprehensive curriculum increased the scholarly output of residents and helped enrich the scholarship culture in the residency program.
Interpreter mediation in statutory mental health assessments: A scoping review
Authors: Rodríguez-Vicente Natalia , Young Alys , Vicary Sarah , Napier Jemina , Tipton Rebecca , Hulme Celia
Published: September 2024

This interdisciplinary scoping review addresses the involvement of spoken and signed language interpreters in statutory mental health assessments. Specifically, this inquiry seeks to identify and review pre-existing literature concerning the barriers to and facilitators of effective practice in interpreter-mediated statutory mental health assessments, and the extent to which interpreter mediation supports or impedes a person’s legal rights and best interests in this context. An interdisciplinary team applied the revised Joanna Briggs Institute scoping review framework to review 44 items, including empirical and grey literature covering relevant aspects of the available body of knowledge across the fields of social work, mental health, and interpreting studies. The review concludes that there is a lack of direct evidence on interpreting practice in the context of statutory mental health assessments, which is significant considering the high-stakes scenarios that may lead to the deprivation of liberty. The findings suggest that there is insufficient evidence regarding necessary modifications to standard interpreting practices for such assessments, as well as how assessors should adapt their own practice in response to the need for interpreting. This work highlights the need for more focused research on good practices for interpreting within this context and calls for guidance to facilitate effective interprofessional collaboration between interpreters and other professionals engaged in these assessments.
Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity
Authors: Bognàr Tim , Garcia-Rosa Moises , Lalmohamed Arief , Güngör Tayfun , Hauri-Hohl Mathias , Prockop Susan , Oram Layne , Pai Sung-Yun , Brooks Jordan , Savic Rada M. , Dvorak Christopher C. , Long-Boyle Janel R. , Krajinovic Maja , Bittencourt Henrique , Teyssier Anne-Charlotte , Théorêt Yves , Martinez Cary , Egberts Toine C. G. , Morales Erin , Slatter Mary , Cuvelier Geoffrey D. E. , Chiesa Robert , Wynn Robert F. , Coussons Mary , Cicalese Maria P. , Ansari Marc , Long Susan E. , Ebens Christen L. , Lust Hannah , Chaudhury Sonali , Nath Christa E. , Shaw Peter J. , Keogh Steven J. , van der Stoep M. Y. Eileen C. , Bredius Robbert , Lindemans Caroline A. , Boelens Jaap-Jan , Bartelink Imke H.
Published: September 2024

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). The objective of this study was to assess the optimal busulfan exposure before allogeneic HCT for patients with an IEI who received an IV busulfan–based conditioning regimen. Patients from 17 international centers were included. The main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders, and hemophagocytic lymphohistiocytosis (HLH)–related disorders. Busulfan exposure was calculated by individual centers (area under the curve [AUC]CENTER) and re-estimated using a nonlinear mixed–effects model (NONMEM; exposure defined as AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) with CID, 154 (27.4%) with SCID, 101 (18.0%) with HLH-related disorders, and 134 (23.8%) with neutrophil disorders. The median busulfan AUCNONMEM was 69.0 mg × h/L and correlated poorly with the AUCCENTER (r2 = 0.54). In patients with SCID, HLH-related, and neutrophil disorders with a busulfan AUCNONMEM of 70 to 90 mg × h/L, 2-year EFS was superior to <70 mg × h/L, and >90 mg ×h/L. Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg × h/L. For patients with CID, the optimal AUCNONMEM for donor chimerism was found to be >70 mg × h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg × h/L (range, 70-90). Our study stresses the importance of uniformly using a validated population pharmacokinetic model to estimate AUCNONMEM.
Association of PH-Targeted Therapy and Survival in Precapillary PH with mPAP between 21 and 24 mmHg
Authors: Yogeswaran Athiththan , Fünderich Meike , Olschewski Horst , Kovacs Gabor , Kiely David G , Lawrie Allan , Hassoun Paul M. , Balasubramanian Aparna , Konswa Ziad , Pepke-Zaba Joanna , Cannon John , Wilkins Martin R. , Howard Luke , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Seeger Werner , Tello Khodr
Published: September 2024

Introduction

. Pulmonary hypertension (PH) definition was recently changed and led to a new subset of PH patients with mildly impaired pulmonary hemodynamics, characterized by a mean pulmonary artery pressure of 21–24 mmHg and with a pulmonary vascular resistance >2Wood Units. We evaluated the association of PH-targeted therapy and outcome in mild precapillary PH using the PVRI GoDeep meta-registry.

Methods

. All patients with mild precapillary PH (mPAP 21–24 mmHg, PAWP ≤15 mmHg, PVR >2WU) diagnosed with PAH and CTEPH were enrolled. Patients were considered treated if PH-targeted therapy was initiated within 6 months of diagnostic right heart catheterization. Various statistical models, including in-depth sensitivity analyses, were used to examine the association between PH-targeted therapy and transplant-free survival.

Results

. 132 patients with group 1 or group 4 mild PH were identified, of whom 34 patients received PH-targeted therapy. There were no differences in baseline hemodynamics between untreated and treated groups, while treated patients suffered more frequently from renal comorbidities and required long-term oxygen treatment more often. Most prescribed were phosphodiesterase-5-inhibitors. PH-targeted therapy was associated with significantly higher survival rates, compared to those without treatment. Cox-regression analysis revealed significantly reduced hazard ratios among treated patients in Cox-regression analyses adjusted for various confounders. Subgroup analyses in PAH (n=78) similarly indicated higher survival rates and reduced hazard ratios in treated patients.

Conclusion

. PH-targeted therapy may be associated with improved survival in PAH and CTEPH patients with mild PH. To mitigate potential bias of the results due to the retrospective study design, randomized controlled trials are warranted.
Optimal spirometry thresholds for the prediction of chronic airflow obstruction: a multinational longitudinal study
Authors: Lam Abby H.S. , Alhajri Sheikhah A. , Potts James , Harrabi Imed , Anand Mahesh Padukudru , Janson Christer , Nielsen Rune , Agarwal Dhiraj , Malinovschi Andrei , Juvekar Sanjay , Denguezli Meriam , Gislason Thorarinn , Jõgi Rain , Garcia-Larsen Vanessa , Ahmed Rana , Nafees Asaad Ahmed , Koul Parvaiz A. , Aquat-Stewart Althea , Burney Peter , Knox-Brown Ben , Amaral Andre F.S.
Published: September 2024

Introduction

Chronic airflow obstruction is key for COPD diagnosis but strategies for its early detection are limited. We aimed to define the optimal z-score thresholds for spirometry parameters to discriminate chronic airflow obstruction incidence.

Methods

The Burden of Obstructive Lung Disease study is a multinational cohort study. Information on respiratory symptoms was collected and pre- and post-bronchodilator spirometry was performed at baseline. Eighteen study sites were followed up with repeat measurements after a median of 8.4 years. We converted lung function measurements into z-scores using the Third National Health and Nutrition Survey reference equations. We used the Youden index to calculate the optimal z-score thresholds for discriminating chronic airflow obstruction incidence. We further examined differences by smoking status.

Results

We analysed data from 3057 adults (57% females, mean age: 51 years at baseline). Spirometry parameters were good at discriminating chronic airflow obstruction incidence (AUC 0.80–0.84), while respiratory symptoms performed poorly. The optimal z-score threshold was identified for pre-bronchodilator FEV1/FVC <-1.336, equivalent to the 9th percentile (sensitivity: 78%, specificity: 72%). All z-score thresholds associated with a lower post-bronchodilator FEV1/FVC and greater odds of chronic airflow obstruction at follow-up. The risk of chronic airflow obstruction was slightly greater for current smokers and, to some extent, never smokers with a pre-bronchodilator FEV1/FVC less than the 9th/10th percentiles at baseline, particularly among males.

Conclusions

Spirometry is better than respiratory symptoms at predicting chronic airflow obstruction incidence. A pre-bronchodilator FEV1/FVC <9th/10th percentiles, particularly among current smokers, could suggest early airflow obstruction or pre-COPD.
Targeting PYK2, entrectinib allays anterior subcapsular cataracts in mice by regulating TGFβ2 signaling pathway
Authors: Ding Xuefei , Li Xiaohe , Fang Rui , Yue Peilin , Jia Yuxuan , Li Enjie , Hu Yayue , Zhou Honggang , Song Xudong
Published: September 2024

Background

Fibrosis cataract occurs in patients receiving cataract extraction. Still, no medication that can cure the disease exists in clinical. This study aims to investigate the effects and mechanisms of Entrectinib on fibrotic cataract in vitro and in vivo.

Methods

The human lens cells line SRA 01/04 and C57BL/6J mice were applied in the study. Entrectinib was used in animals and cells. Cataract severity was assessed by slit lamp and Hematoxylin and Eosin staining. Expression of alpha-smooth muscle actin, fibronectin, and collagen I were examined by real-time quantitative PCR, western blotting, and immunofluorescence. Cell proliferation was evaluated by Cell Counting Kit-8. Cell migration was measured by wound healing and transwell assays. Molecular docking, Drug Affinity Responsive Target Stability, and Cellular Thermal Shift Assay were applied to seek and certify the target of Entrectinib treating fibrosis cataract.

Results

Entrectinib can ameliorate fibrotic cataract in vitro and in vivo. At the RNA and the protein levels, the expression of alpha-smooth muscle actin, collagen I, and fibronectin can be downgraded by Entrectinib, while E-cadherin can be upregulated. The migration and proliferation of cells were inhibited by Entrectinib. Mechanistically, Entrectinib obstructs TGFβ2/Smad and TGFβ2/non-Smad signaling pathways to hinder the fibrosis cataract by targeting PYK2 protein.

Conclusions

Targeting with PYK2, Entrectinib can block TGF-β2/Smad and TGF-β2/non-Smad signaling pathways, lessen the activation of EMT, and alleviate fibrosis cataract. Entrectinib may be a potential treatment for fibrosis cataract in clinic.
First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients
Authors: Yang Zhao , Wang Xiaodan , Niu Mengyue , Wei Qiao , Zhong Huizhu , Li Xiaoyan , Yuan Weihong , Xu Wenli , Zhu Shuo , Yu Shengyuan , Liu Jun , Yan Jianzhou , Kang Wenyan , Huang Peijian
Published: September 2024

Background

Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.

Methods

This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.

Results

By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.

Conclusions

In the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.

Trial registration

Clinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.

Graphical Abstract
Occlusive retinal vasculitis associated with intravitreal Faricimab injections
Authors: Reichel Felix F. , Kiraly Peter , Vemala Roopa , Hornby Stella , De Silva Samantha R. , Fischer M. Dominik
Published: September 2024

Purpose

We describe a case of occlusive vasculitis associated with intravitreal Faricimab (Vabysmo) injections.

Methods

A retrospective case report.

Results

A 52-year old man treated with monthly Faricimab injections for diabetic macula oedema presented with sudden reduced vision, new retinal hemorrhages, significant retinal vascular occlusions and ischemia. After screening for differential diagnoses was unremarkable, the patient was treated with oral and intravitreal steroid therapy under which the occlusive vasculitis was stabilized.

Conclusion

Occlusive vasculitis, though rare, is a potential complication of Faricimab therapy. Comprehensive reporting and large-scale analyses are essential to better understand and manage this adverse event.
Mugen-UMAP: UMAP visualization and clustering of mutated genes in single-cell DNA sequencing data
Authors: Li Teng , Zou Yiran , Li Xianghan , Wong Thomas K. F. , Rodrigo Allen G.
Published: September 2024

Background

The application of Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization has revolutionized the analysis of single-cell RNA expression and population genetics. However, its potential in single-cell DNA sequencing data analysis, particularly for visualizing gene mutation information, has not been fully explored.

Results

We introduce Mugen-UMAP, a novel Python-based program that extends UMAP’s utility to single-cell DNA sequencing data. This innovative tool provides a comprehensive pipeline for processing gene annotation files of single-cell somatic single-nucleotide variants and metadata to the visualization of UMAP projections for identifying clusters, along with various statistical analyses. Employing Mugen-UMAP, we analyzed whole-exome sequencing data from 365 single-cell samples across 12 non-small cell lung cancer (NSCLC) patients, revealing distinct clusters associated with histological subtypes of NSCLC. Moreover, to demonstrate the general utility of Mugen-UMAP, we applied the program to 9 additional single-cell WES datasets from various cancer types, uncovering interesting patterns of cell clusters that warrant further investigation. In summary, Mugen-UMAP provides a quick and effective visualization method to uncover cell cluster patterns based on the gene mutation information from single-cell DNA sequencing data.

Conclusions

The application of Mugen-UMAP demonstrates its capacity to provide valuable insights into the visualization and interpretation of single-cell DNA sequencing data. Mugen-UMAP can be found at https://github.com/tengchn/Mugen-UMAP
Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications
Authors: Zhang Qiang , Dimairo Munyaradzi , Julious Steven A. , Lewis Jen , Yu Zihang
Published: September 2024

Background

An adaptive design allows modifying the design based on accumulated data while maintaining trial validity and integrity. The final sample size may be unknown when designing an adaptive trial. It is therefore important to consider what sample size is used in the planning of the study and how that is communicated to add transparency to the understanding of the trial design and facilitate robust planning. In this paper, we reviewed trial protocols and grant applications on the sample size reporting for randomised adaptive trials.

Method

We searched protocols of randomised trials with comparative objectives on ClinicalTrials.gov (01/01/2010 to 31/12/2022). Contemporary eligible grant applications accessed from UK publicly funded researchers were also included. Suitable records of adaptive designs were reviewed, and key information was extracted and descriptively analysed.

Results

We identified 439 records, and 265 trials were eligible. Of these, 164 (61.9%) and 101 (38.1%) were sponsored by industry and public sectors, respectively, with 169 (63.8%) of all trials using a group sequential design although trial adaptations used were diverse.

The maximum and minimum sample sizes were the most reported or directly inferred (n = 199, 75.1%). The sample size assuming no adaptation would be triggered was usually set as the estimated target sample size in the protocol. However, of the 152 completed trials, 15 (9.9%) and 33 (21.7%) had their sample size increased or reduced triggered by trial adaptations, respectively.

The sample size calculation process was generally well reported in most cases (n = 216, 81.5%); however, the justification for the sample size calculation parameters was missing in 116 (43.8%) trials. Less than half gave sufficient information on the study design operating characteristics (n = 119, 44.9%).

Conclusion

Although the reporting of sample sizes varied, the maximum and minimum sample sizes were usually reported. Most of the trials were planned for estimated enrolment assuming no adaptation would be triggered. This is despite the fact a third of reported trials changed their sample size. The sample size calculation was generally well reported, but the justification of sample size calculation parameters and the reporting of the statistical behaviour of the adaptive design could still be improved.
Hepatitis C virus attributable liver cancer in the country of Georgia, 2015–2019: a case–control study
Authors: Surguladze Sophia , Armstrong Paige A. , Beckett Geoff A. , Shadaker Shaun , Gamkrelidze Amiran , Tsereteli Maia , Getia Vladimer , Asamoah Benedict Oppong
Published: September 2024

Background

Hepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program’s impact. This study assesses HCV infection-attributable HCC in the Georgian population.

Methods

This case–control study utilized HCV programmatic and Georgian Cancer Registry data from 2015–2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically.

Results

The total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97–25.37), and the odds of developing HCC was 16.84 (95% CI 12.01–23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone.

Conclusion

HCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia’s high HCV burden, increased HCC monitoring in HCV-infected patients is needed.