bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the causal effect of dexamethasone versus hydrocortisone on the neutrophil- lymphocyte ratio in critically ill COVID-19 patients from Tygerberg Hospital ICU using TMLE method
Authors: Nkuhairwe Ivan Nicholas , Esterhuizen Tonya Marianne , Sigwadhi Lovemore Nyasha , Tamuzi Jacques Lukenze , Machekano Rhoderick , Nyasulu Peter S. 
Published: November 2024

Abstract
Background
Causal inference from observational studies is an area of interest to researchers, advancing rapidly over the years and with it, the methods for causal effect estimation. Among them, Targeted Maximum Likelihood estimation (TMLE) possesses arguably the most outstanding statistical properties, and with no outright treatment for COVID-19, there was an opportunity to estimate the causal effect of dexamethasone versus hydrocortisone upon the neutrophil-lymphocyte ratio (NLR), a vital indicator for disease progression among critically ill COVID-19 patients.

Methods
TMLE variations were used in the analysis. Super Learner (SL), Bayesian Additive Regression Trees (BART) and parametric regression (PAR) were implemented to estimate the average treatment effect (ATE).

Results
The study had 168 participants, 128 on dexamethasone and 40 on hydrocortisone. The mean causal difference in NLR on day 5; ATE [95% CI]: from SL-TMLE was − 0.309 [-3.800, 3.182] BART-TMLE 0.246 [-3.399, 3.891] and PAR-TMLE 1.245 [-1.882, 4372]. The ATE of dexamethasone versus hydrocortisone on NLR was not statistically significant since the confidence interval included zero.

Conclusion
The effect of dexamethasone is not significantly different from that of hydrocortisone on NLR in critically ill COVID-19 patients admitted to ICU. This implies that the difference in effect on NLR between the two drugs is due to random chance. TMLE remains an outstanding approach for causal analysis of observational studies with the ability to be augmented with multiple prediction approaches.
Effect of linex treatment on IFN-γ and IL-4 in mice infected with Trichinella
Authors: Atta Shimaa Attia , Fahmy Zeinab H. , Selim Eman A.H. , Aboushousha Tarek , Mostafa Reham Refaat 
Published: November 2024

AbstractTrichinellosis is a zoonotic, foodborne parasitic infection causing muscle damage. This study investigated the potential therapeutic effects of the commercially available probiotic treatment Linex, both alone and in combination with Albendazole (ALB), on the intestinal and muscular stages of Trichinella spiralis infection in mice, assessing outcomes through parasitological, immunological, and histopathological measures. This study is the first to demonstrate the synergistic effect of combining the commercially available probiotic Linex with Albendazole for trichinellosis treatment. By enhancing both parasitological and immunological outcomes, this combined therapy not only significantly reduces parasite burden but also modulates the immune response, shifting it toward a protective Th1 profile. In parasitological terms, the highest adult and larval count reduction was observed in combined Linex and Albendazole treatment (100%, 97.7%) respectively. Lesser percentage of reduction were recorded in Linex alone therapy (43.2%, 88.4%) respectively. Histopathologically there was amelioration of the inflammatory cellular infiltration in all treated groups with best results in combined Linex and Albendazole treatment. Immunologically, serum IFN-γ levels increased significantly in all treated groups with highest levels in combined Linex and Albendazole treatment, while IL-4 and IL-13 level decreased significantly in all treated groups with best results observed in Linex alone treatment. To conclude; combined Linex and Albendazole treatment of mice infected with T. spirals could ameliorate the infection and improve the immune response.
Three-dimensional digital imaging analysis of the palatal bone thickness for orthodontic mini-implant insertion – determination of the safe zone and angulation
Authors: Schubert Hanna , Matta Ragai , Seidel Anna , Adler Werner , Wichmann Manfred , Kesting Marco , Lutz Rainer 
Published: November 2024

Abstract
Background
In order to successfully perform orthodontic mini-implant procedures successfully for the subsequent anchoring of orthodontic appliances, it is crucial to know the palatal bone thickness. This is usually assessed using two-dimensional radiographs. The purpose of this study was to use a three-dimensional digital imaging measurement method to provide information on palatal bone volume and bone thickness and to make recommendations on the optimal and safe insertion site and angle for palatal mini-implants.

Methods
For this observational, cross-section study, pre-existing cone beam computed tomography scans of 184 patients were converted into 3D Standard Tessellation Language (STL) models of the maxilla. The area between the canine and the first molar was divided into 6 regions of interest (ROIs), three on the left side of the palate and three on the right side. The bone thickness of the palate was analyzed volumetrically and linearly while simulating different mini-implant insertion angles of 0°, 10°, 20° and 30° degrees relative to the palatal surface.

Results
Among the ROIs, the greatest mean bone thickness was observed in the region of the first premolars with a mean distance (MD) of 10.44 ± 2.53 mm and decreased from anterior to posterior (MD: 3.44 ± 1.16 mm). The highest volume (Vol) values were also measured in the anterior palatal region (Vol: 1127.26 ± 483.91 mm3), while there was also a decrease in the posterior region (Vol: 394.36 ± 180.22 mm3). Regarding the simulated palatal mini-implant insertion sites, the greatest bone thickness was found in the anterior region, at the level of the canines with an angle of 0° (MD: 12.25 ± 3.75 mm). In the more posterior region, at the level between the first and second premolars, the greatest bone thickness was observed at an angle of 30° (MD: 7.93 ± 3.81 mm). Gender differences were found.

Conclusion
This clinical study showed that the paramedian region at the level of the first premolar is the safest site for orthodontic mini-implant placement as evaluated by three-dimensional measurements. The results showed that implant insertion angle, gender and age are important aspects to consider when planning and inserting orthodontic palatal mini-implants.

Trial registration
N.a.
Fear of progression in patients with acute myocardial infarction: a cross-sectional study
Authors: Wang Xinghui , Jiang Nan , Chen Shuoxin , Tuerdi Subinuer , Yang Jiayu , Yan Rong , He Li , Wang Jiajia , Li Yuewei 
Published: November 2024

Abstract
Background
Acute myocardial infarction (AMI) is the most serious manifestation of coronary artery disease. At present, existing treatments cannot change the risk factors for the occurrence of the disease, so patients are prone to fear of progression or recurrence, and studies have shown that excessive fear will cause patients to over-examine, mental abnormalities, suicide and other behaviors, increase unnecessary medical care costs and the social medical burden. Thus to investigate the current situation of progression fear in patients with Acute Myocardial Infarction (AMI) admitted to hospital in stable stage and analyze its influencing factors.

Methods
This is a cross-sectional study. In this study, 160 AMI patients admitted to the Department of Cardiology of a 3 A hospital in Changchun from November 2022 to April 2023 were selected as the research sample by a convenient sampling method. Patients completed the general information questionnaire, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Brief Illness Perception Questionnaire (BIPQ), the Medical Coping Modes Questionnaire (MCSQ), the Social Support Rating Scale (SSRS), and the Positive Psychological Questionnaire (PPQ) at the time of stable condition. Using SPSS 25.0 software for data analysis, statistical methods mainly include descriptive statistics, analysis of variance, Pearson correlation analysis and multiple linear regression analysis.

Results
A total of 160 subjects were included, among which the score of simplified fear of progression scale was (33.43 ± 7.09), and the incidence of disorder of fear of progression was 50.60%. The influencing factors included gender (Beta = 0.118, P<0.05), disease perception (Beta = 0.445, P<0.001), psychological capital (Beta=-0.252, P<0.05) and resignation (Beta = 0.167, P < 0.05).

Conclusion
The overall level of fear of progression in patients with AMI at the stable stage of hospitalization is above the medium level. Nursing staff should focus on AIM patients suffering from multiple diseases and lacking awareness of their own diseases, and provide personalized health guidance and psychological nursing targeted to improve patients’ rehabilitation, quality of life and FoP level.
Characterizing the pharmacological interaction of the antimalarial combination artefenomel-piperaquine in healthy volunteers with induced blood-stage Plasmodium falciparum to predict efficacy in patients with malaria
Authors: Abd-Rahman Azrin N. , Kaschek Daniel , Kümmel Anne , Webster Rebecca , Potter Adam J. , Odedra Anand , Woolley Stephen D. , Llewellyn Stacey , Webb Lachlan , Marquart Louise , Chalon Stephan , Gaaloul Myriam El , McCarthy James S. , Möhrle Jörg J. , Barber Bridget E. 
Published: November 2024

Abstract

Background

The combination antimalarial artefenomel-piperaquine failed to achieve target efficacy in a phase 2b study in Africa and Vietnam. We retrospectively evaluated whether characterizing the pharmacological interaction of this antimalarial combination in a volunteer infection study (VIS) would have enabled prediction of the phase 2b study results.

Methods
Twenty-four healthy adults enrolled over three consecutive cohorts were inoculated with Plasmodium falciparum-infected erythrocytes on day 0. Participants were randomized within each cohort to one of seven dose combination groups and administered a single oral dose of artefenomel-piperaquine on day 8. Participants received definitive antimalarial treatment with artemether-lumefantrine upon parasite regrowth or on day 42 ± 2. The general pharmacodynamic interaction (GPDI) model implemented in the Bliss Independence additivity criterion was developed to characterize the pharmacological interaction between artefenomel and piperaquine. Simulations based on the model were performed to predict the outcomes of the phase 2b combination study.

Results
For a dose of 800 mg artefenomel administered with 640 mg, 960 mg, or 1440 mg piperaquine, the simulated adequate parasitological response at day 28 (APR28), incorporating actual patient pharmacokinetic (PK) data from the phase 2b trial, was 69.4%, 63.9%, and 74.8%, respectively. These results closely matched the observed APR28 in the phase 2b trial of 67.0%, 65.5%, and 75.4%, respectively.

Conclusions
These results indicate that VIS offer an efficient means for informing antimalarial combination trials conducted in the field, potentially expediting clinical development.

Trial registration
This study was registered on ClinicalTrials.gov on 11 May 2018 with registration number NCT03542149.
Facilitators and challenges in collaboration between public health units and faith-based organizations to promote COVID-19 vaccine confidence in Ontario
Authors: Kadio Kadidiatou , Blake-Hepburn Denessia , Song Melodie Yunju , Karbasi Anna , Noad Elizabeth Estey , Abdi Samiya , Peer Nazia , Fadel Shaza A. , Allin Sara , Ataullahjan Anushka , Di Ruggiero Erica 
Published: November 2024

Abstract
Background
Equitable access to vaccination remains a concern, particularly among population groups made structurally vulnerable. These population groups reflect the diversity of communities that are confronted with structural barriers caused by systemic racism and oppression and result in them experiencing suffer disadvantage and discrimination based on citizenship, race, ethnicity, ancestry, religion, spiritual beliefs, and/or gender identity. In Canada, Ontario public health units (PHUs) engage with faith-based organizations (FBOs) to improve vaccine confidence among populations made structurally vulnerable. This study explores the factors that facilitate and hinder engagement in the implementation of vaccine confidence promoting interventions, and challenges associated with working with FBOs.

Methods
In-depth interviews were conducted with 18 of the 34 Ontario PHUs who expressed an interest. Braun and Clarke’s “experiential” approach was used to explore the realities of PHUs’ contextual experiences and perspectives.

Results
The results showed that receptivity and openness of PHUs to learn from FBOs, previous experience working with religious communities and FBOs, ongoing relations based on respect of different beliefs and opinions on the vaccines, leveraging the support of trusted faith leaders among communities and communications strategy adapted and sensitive to the needs of the community was facilitators to community involvement in the prevention and control of COVID-19. On the other hand, factors both internal and external to the PHUs have often posed challenges to collaboration with the FBOs. Internal factors include low operational capacity of PHU like insufficient human and financial resources, weak analytical capacity, ambiguity in the roles and responsibilities of the different actors. Some external challenges issues were related to the provincial level and the Ministry of Health, while others were related to FBOs. For example, faith-based and collective beliefs promoting vaccine hesitancy have resulted in resistance from some religious communities when PHUs have reached out to collaborate.

Conclusions
Engaging with faith-based communities is an ongoing process that requires time, flexibility, and patience, but it is necessary to improve vaccine confidence and equity access among population groups made structurally vulnerable. Lessons learned from this research can guide the implementation of future vaccination programs.
INSIGHT-2: mechanistic studies into pregnancy complications and their impact on maternal and child health—study protocol
Authors: Valensin Carlotta , Côté Emilie J. M. , Pereira-Carvalho Daniela , Gardner Rachael A. , Nishku Glen , Giles Caitlin L. , Gill Carolyn , Brockbank Anna , Story Lisa , Shennan Andrew H. , Suff Natalie , Gibbons Deena L. , Tribe Rachel M. 
Published: November 2024

Abstract
Background
Pregnancy and early childhood cohorts provide a framework for investigating the complex interplay between early-life exposures and health outcomes, thereby informing prevention strategies and interventions to improve maternal and child health. In this paper, we outline the objectives, methodologies and expected contributions of INSIGHT-2, a comprehensive cohort study dedicated to advancing our understanding of pregnancy and pregnancy complications towards improving the health and well-being of mothers and their offspring.

Methods
Over the course of 5 years, the study aims to establish a diverse cohort of 1700 pregnant women and to follow up their children up to 2 years of age. Recruitment targets participants with healthy pregnancies, preexisting conditions, and/or risk factors for pregnancy complications or later child health problems. Clinical and lifestyle data and a range of biological samples will be collected, providing a comprehensive resource for biomarker investigations and cross-sectional analyses. It is anticipated that the cohort will continue beyond this initial 5-year plan.

Discussion
By gathering a wide range of biological samples and using diverse analytical techniques, this study supports broad participation, potential replication and collaboration across various sites. The extensive collection of longitudinal data and samples not only facilitates current investigations but also establishes a biobank for future research. The exploration of pre-pregnancy and pregnancy factors that may contribute to disease processes and impact fetal well-being and future health will provide a comprehensive picture of disease mechanisms in both mothers and children, facilitating the identification of biomarkers for the prediction, diagnosis, and management of pregnancy complications. Additionally, our diverse population allows for the capture of various pregnancy complications and outcomes, enhancing external validity and addressing health disparities. This comprehensive design ultimately aims to improve maternal and child health outcomes by providing a valuable longitudinal study of the relationships among the in utero environment, pregnancy management, and long-term maternal and child health, ensuring that findings are relevant and beneficial to a broader population.
A therapeutic approach to pantothenate kinase associated neurodegeneration: a pilot study
Authors: Pereira Alessandra , Fischinger Moura de Souza Carolina , Álvarez-Córdoba Mónica , Reche-López Diana , Sánchez-Alcázar José Antonio 
Published: November 2024

Abstract
Background
Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA disorders. The diagnosis of PKAN is established with clinical features and the “eye of the tiger” sign identified on brain MRI and the identification of biallelic pantothenate kinase 2 (PANK2) pathogenic variants on molecular genetic testing. PANK2 catalyzes the first reaction of coenzyme A (CoA) biosynthesis, thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.

Methods
In this manuscript, we examined the effect of a multitarget complex supplements (pantothenate, pantethine, omega-3 and vitamin E) on in vitro patient-derived cellular models and the clinical outcome of the adjuvant supplements in combination with the baseline neurological medication in three PKAN patients.

Results
Multitarget complex supplements significantly reduced iron accumulation and increased PANK2 and ACP expression levels in the cellular models derived from all three PKAN patients. In addition, the adjunct treatment to the standard neurological medication improved or stabilized the clinical symptoms of patients.

Conclusions
Our results suggest that multitarget complex supplements can be clinically useful as augmentation therapy for PKAN patients harboring pathogenic variants with residual enzyme levels.
Trial registration: CAAE: 58219522.6.0000.5330. Registered 25 May 2022—Retrospectively registered, https://plataformabrasil.saude.gov.br/visao/pesquisador/gerirPesquisa/gerirPesquisaAgrupador.jsf.
TGFβ family signaling in human stem cell self-renewal and differentiation
Authors: Liu Sijia , Ren Jiang , Hu Yanmei , Zhou Fangfang , Zhang Long 
Published: November 2024

AbstractHuman stem cells are undifferentiated cells with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in the development and maintenance of diverse tissues and organs. The microenvironment of stem cell provides crucial factors and components that exert significant influence over the determination of cell fate. Among these factors, cytokines from the transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin and Nodal, have been identified as important regulators governing stem cell maintenance and differentiation. In this review, we present a comprehensive overview of the pivotal roles played by TGFβ superfamily signaling in governing human embryonic stem cells, somatic stem cells, induced pluripotent stem cells, and cancer stem cells. Furthermore, we summarize the latest research and advancements of TGFβ family in various cancer stem cells and stem cell-based therapy, discussing their potential clinical applications in cancer therapy and regeneration medicine.
A lightweight approach to real-time speaker diarization: from audio toward audio-visual data streams
Authors: Kynych Frantisek , Cerva Petr , Zdansky Jindrich , Svendsen Torbjørn , Salvi Giampiero 
Published: November 2024

AbstractThis manuscript deals with the task of real-time speaker diarization (SD) for stream-wise data processing. Therefore, in contrast to most of the existing papers, it considers not only the accuracy but also the computational demands of individual investigated methods. We first propose a new lightweight scheme allowing us to perform speaker diarization of streamed audio data. Our approach utilizes a modified residual network with squeeze-and-excitation blocks (SE-ResNet-34) to extract speaker embeddings in an optimized way using cached buffers. These embeddings are subsequently used for voice activity detection (VAD) and block-online k-means clustering with a look-ahead mechanism. The described scheme yields results similar to the reference offline system while operating solely on a CPU with a low real-time factor (RTF) below 0.1 and a constant latency of around 5.5 s. In the next part of the work, our research moves toward much more demanding and complex real-time processing of audio-visual data streams. For this purpose, we extend the above-mentioned scheme for audio data processing by adding an audio-video module. This module utilizes SyncNet combined with visual embeddings for identity tracking. Our resulting multi-modal SD framework then combines the outputs from audio and audio-video modules by using a new overlap-based fusion strategy. It yields diarization error rates that are competitive with the existing state-of-the-art offline audio-visual methods while allowing us to process various audio-video streams, e.g., from Internet or TV broadcasts, in real-time using GPU and with the same latency as for audio data processing.