bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane
Authors: El-Mansi Sammy , Mitchell Tom P. , Mobayen Golzar , McKinnon Thomas A. J. , Miklavc Pika , Frick Manfred , Nightingale Thomas D. 
Published: April 2024

Abstract
Blood endothelial cells control the hemostatic and inflammatory response by secreting von Willebrand factor (VWF) and P-selectin from storage organelles called Weibel-Palade bodies (WPBs). Actin-associated motor proteins regulate this secretory pathway at multiple points. Before fusion, myosin Va forms a complex that anchors WPBs to peripheral actin structures, allowing for the maturation of content. After fusion, an actomyosin ring/coat is recruited and compresses the WPB to forcibly expel the largest VWF multimers. Here, we provide, to our knowledge, the first evidence for the involvement of class I myosins during regulated VWF secretion. We show that the unconventional myosin-1C (Myo1c) is recruited after fusion via its pleckstrin homology domain in an actin-independent process. This provides a link between the actin ring and phosphatidylinositol 4,5-bisphosphate (PIP2) at the membrane of the fused organelle and is necessary to ensure maximal VWF secretion. This is an active process requiring Myo1c ATPase activity because inhibition of class I myosins using the inhibitor pentachloropseudilin or expression of an ATPase-deficient Myo1c rigor mutant perturbs the expulsion of VWF and alters the kinetics of the exocytic actin ring. These data offer a novel insight into the control of an essential physiological process and provide a new way in which it can be regulated.
Exploring combinations of dimensionality reduction, transfer learning, and regularization methods for predicting binary phenotypes with transcriptomic data
Authors: Oshternian S. R. , Loipfinger S. , Bhattacharya A. , Fehrmann R. S. N. 
Published: April 2024

Abstract
Background
Numerous transcriptomic-based models have been developed to predict or understand the fundamental mechanisms driving biological phenotypes. However, few models have successfully transitioned into clinical practice due to challenges associated with generalizability and interpretability. To address these issues, researchers have turned to dimensionality reduction methods and have begun implementing transfer learning approaches.

Methods
In this study, we aimed to determine the optimal combination of dimensionality reduction and regularization methods for predictive modeling. We applied seven dimensionality reduction methods to various datasets, including two supervised methods (linear optimal low-rank projection and low-rank canonical correlation analysis), two unsupervised methods [principal component analysis and consensus independent component analysis (c-ICA)], and three methods [autoencoder (AE), adversarial variational autoencoder, and c-ICA] within a transfer learning framework, trained on > 140,000 transcriptomic profiles. To assess the performance of the different combinations, we used a cross-validation setup encapsulated within a permutation testing framework, analyzing 30 different transcriptomic datasets with binary phenotypes. Furthermore, we included datasets with small sample sizes and phenotypes of varying degrees of predictability, and we employed independent datasets for validation.

Results
Our findings revealed that regularized models without dimensionality reduction achieved the highest predictive performance, challenging the necessity of dimensionality reduction when the primary goal is to achieve optimal predictive performance. However, models using AE and c-ICA with transfer learning for dimensionality reduction showed comparable performance, with enhanced interpretability and robustness of predictors, compared to models using non-dimensionality-reduced data.

Conclusion
These findings offer valuable insights into the optimal combination of strategies for enhancing the predictive performance, interpretability, and generalizability of transcriptomic-based models.
Plant immunity suppression by an β-1,3-glucanase of the maize anthracnose pathogen Colletotrichum graminicola
Authors: Gu Xiaoyu , Cao Zhiyan , Li Zhiqiang , Yu Haiyue , Liu Wende 
Published: April 2024

Abstract
Background
Many phytopathogens secrete a large number of cell wall degrading enzymes (CWDEs) to decompose host cell walls in order to penetrate the host, obtain nutrients and accelerate colonization. There is a wide variety of CWDEs produced by plant pathogens, including glycoside hydrolases (GHs), which determine the virulence, pathogenicity, and host specificity of phytopathogens. The specific molecular mechanisms by which pathogens suppress host immunity remain obscure.

Result
In this study, we found that CgEC124 encodes a glycosyl hydrolase with a signal peptide and a conserved Glyco_hydro_cc domain which belongs to glycoside hydrolase 128 family. The expression of CgEC124 was significantly induced in the early stage of Colletotrichum graminicola infection, especially at 12 hpi. Furthermore, CgEC124 positively regulated the pathogenicity, but it did not impact the vegetative growth of mycelia. Ecotopic transient expression of CgEC124 decreased the disease resistance and callose deposition in maize. Moreover, CgEC124 exhibited the β-1,3-glucanase activity and suppresses glucan-induced ROS burst in maize leaves.

Conclusions
Our results indicate that CgEC124 is required for full virulence of C. graminicola but not for vegetative growth. CgEC124 increases maize susceptibility by inhibiting host reactive oxygen species burst as well as callose deposition. Meanwhile, our data suggests that CgEC124 explores its β-1,3-glucanase activity to prevent induction of host defenses.
Assessment and management of chronic insomnia disorder: an algorithm for primary care physicians
Authors: Selsick Hugh , Heidbreder Anna , Ellis Jason , Ferini-Strambi Luigi , García-Borreguero Diego , Leontiou Chrysoula , Mak Michael S.B. , O’Regan David , Parrino Liborio 
Published: April 2024

Abstract
Background
Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers.

Methods
A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements.

Results
Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients’ needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use.

Conclusion
The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management.
A practical approach to screening for carbapenemase-producing Enterobacterales– views of a group of multidisciplinary experts from English hospitals
Authors: Jenkins DR. , Auckland C. , Chadwick C. , Dodgson AR. , Enoch DA. , Goldenberg SD. , Hussain A. , Martin J. , Spooner E. , Whalley T. 
Published: April 2024

Abstract
Introduction
Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges.

Methods
A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE.

Key findings
Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks.

Conclusion
Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources– such as upscaled screening– to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.
Predicting chronic kidney disease progression with artificial intelligence
Authors: Isaza-Ruget Mario A. , Yomayusa Nancy , González Camilo A. , H. Catherine Alvarado , de Oro V. Fabio A. , Cely Andrés , Murcia Jossie , Gonzalez-Velez Abel , Robayo Adriana , Colmenares-Mejía Claudia C. , Castillo Andrea , Conde María I. 
Published: April 2024

Abstract
Background
The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3–5 CKD.

Methods
This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT.

Results
Three prediction models were developed—Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,— Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively.

Conclusion
The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.
Clinical features and comprehensive treatment of persistent corneal epithelial dysfunction after cataract surgery
Authors: Xiao Xianwen , Lin Yuan , Fang Xie , Xie Zhiwen , Luo Shunrong , Wu Huping 
Published: April 2024

Abstract
Objective
Evaluation of clinical efficacy and safety of tobramycin/dexamethasone eye ointment in treating persistent corneal epithelial dysfunction (PED) after cataract surgery.

Methods
26 cases diagnosed as PED after cataract surgery accept the tobramycin/dexamethasone ophthalmic ointment and intense pulse light treatment in the Xiamen University of Xiamen eye center between September 2016 and April 2022 were retrospectively analyzed, mainly including clinical manifestations, characteristics of morphological changes imaged by in vivo confocal microscopy, meibomian glands infrared photography, lipid layer thickness (LLT), management and therapeutic effects.

Results
There were 26 eyes, include 8(35%) males and 15(65%) females with an average age of 69.6 ± 5.2 years(50 to 78 years). The mean hospitalization time was (18.4 ± 7.5) days after cataract surgery. Twenty patients had meibomian gland dysfunction. Infrared photography revealed varying loss in the meibomian glands, with a mean score of 3.8 ± 1.2 for gland loss. The mean LLT was 61.6 ± 8.4 nm. After treatment, 20 patients were cured, and 3 received amniotic membrane transplantation. After treatment, the uncorrected visual acuity (UCVA) and best-corrected vision activity (BCVA) improved (P < 0.001), and there was no significant difference in intraocular pressure (IOP) before and after treatment (P > 0.05).

Conclusions
The early manifestation of PED after surgery is punctate staining of the corneal epithelium. Tobramycin and dexamethasone eye ointment bandages have a good repair effect. The meibomian gland massage combined with intense pulse light treatment can effectively shorten the course of the disease.
Irisin combined index to diagnose central precocious puberty in girls: a cross-sectional study
Authors: Wang Jie , Tang Yongquan , Chen Guanyu , Yang Mingming , Gao Qian , Wang Yingdan , Zhou Wendi 
Published: April 2024

Abstract
Background
To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls.

Methods
In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test.

Results
Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index.

Conclusions
Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.
Asbestos ban policies and mesothelioma mortality in Greece
Authors: Gogou Evdoxia , Hatzoglou Chryssi , Siachpazidou Dimitra , Zarogiannis Sotirios G. , Gourgoulianis Konstantinos I. 
Published: April 2024

Abstract
Background
Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece’s mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.

Methods
Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).

Results
From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males’ ASMR and the whole population’s ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000–2009 and 2010–2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000–2009) to 0.31/100000person-years (2010–2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.

Conclusions
In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.

Trial registration
Not applicable.
A new neonatal BCG vaccination pathway in England: a mixed methods evaluation of its implementation
Authors: Jones Koren , Chisnall Georgia , Crocker-Buque Tim , Elliman David , Horwood Jeremy , Mounier-Jack Sandra , Campbell Colin NJ , Saliba Vanessa , Chantler Tracey 
Published: April 2024

Abstract
Introduction
The introduction of a national evaluation of newborn screening for Severe Combined Immunodeficiency (SCID) in England triggered a change to the selective Bacillus Calmette-Guerin (BCG) vaccination programme delivery pathway, as this live attenuated vaccine is contraindicated in infants with SCID. The neonatal BCG vaccination programme is a targeted programme for infants at increased risk of tuberculosis and used to be offered shortly after birth. Since September 2021 the BCG vaccine is given to eligible infants within 28 days of birth, when the SCID screening outcome is available. We explore the experiences of those implementing the new pathway, and how they made sense of, engaged with, and appraised the change.

Methods
A mixed-methods evaluation was conducted between October 2022 and February 2023. This involved national online surveys with BCG commissioners and providers and qualitative semi-structured interviews with commissioners, providers, and Child Health Information System stakeholders in two urban areas. Survey data was analysed using descriptive statistics and interview data was analysed thematically. The data was triangulated using Normalization Process Theory as a guiding framework.

Results
Survey respondents (n = 65) and qualitative interviewees (n = 16) revealed that making sense of the new pathway was an iterative process. Some expressed a desire for more direction on how to implement the new pathway. The perceived value of the change varied from positive, ambivalent, to concerned. Some felt well-prepared and that improvements to data capture, eligibility screening, and accountably brought by the change were valuable. Others were concerned about the feasibility of the 28-day target, reductions in vaccination coverage, increased resource burden, and the outcome of the SCID evaluation. New collaborations and communities of practice were required to facilitate the change. Three main challenges in implementing the pathway and meeting the 28-day vaccination target were identified: appointment non-attendance; appointment and data systems; and staffing and resourcing. Feedback mechanisms were informal and took place in tandem with implementation.

Conclusion
The new NHS neonatal BCG service specification has created an effective structure for monitoring and managing the BCG vaccination programme, but further work is required to support delivery of the 28-day vaccination target and improve uptake rates.
The risk of contact between visitors and Borrelia burgdorferi-infected ticks is associated with fine-scale landscape features in a southeastern Canadian nature park
Authors: Dumas Ariane , Bouchard Catherine , Drapeau Pierre , Lindsay L. Robbin , Ogden Nicholas H. , Leighton Patrick A. 
Published: April 2024

Abstract
Background
Infectious diseases are emerging across temperate regions of the world, and, for some, links have been made between landscapes and emergence dynamics. For tick-borne diseases, public parks may be important exposure sites for people living in urbanized areas of North America and Europe. In most cases, we know more about the ecological processes that determine the hazard posed by ticks as disease vectors than we do about how human population exposure varies in urban natural parks.

Methods
In this study, infrared counters were used to monitor visitor use of a public natural park in southern Quebec, Canada. A risk index representing the probability of encounters between humans and infected vectors was constructed. This was done by combining the intensity of visitor trail use and the density of infected nymphs obtained from field surveillance. Patterns of risk were examined using spatial cluster analysis. Digital forest data and park infrastructure data were then integrated using spatially explicit models to test whether encounter risk levels and its components vary with forest fragmentation indicators and proximity to park infrastructure.

Results
Results suggest that, even at a very fine scales, certain landscape features and infrastructure can be predictors of risk levels. Both visitors and Borrelia burgdorferi-infected ticks concentrated in areas where forest cover was dominant, so there was a positive association between forest cover and the risk index. However, there were no associations between indicators of forest fragmentation and risk levels. Some high-risk clusters contributed disproportionately to the risk distribution in the park relative to their size. There were also two high-risk periods, one in early summer coinciding with peak nymphal activity, and one in early fall when park visitation was highest.

Conclusions
Here, we demonstrate the importance of integrating indicators of human behaviour visitation with tick distribution data to characterize risk patterns for tick-borne diseases in public natural areas. Indeed, understanding the environmental determinants of human-tick interactions will allow organisations to deploy more effective risk reduction interventions targeted at key locations and times, and improve the management of public health risks associated with tick-borne diseases in public spaces.