bluuebunny/crossref_metadata_2025_split huggingface dataset:
LPA1 antagonist BMS-986020 changes collagen dynamics and exerts antifibrotic effects in vitro and in patients with idiopathic pulmonary fibrosis
Authors: Decato Benjamin E. , Leeming Diana Julie , Sand Jannie Marie Bülow , Fischer Aryeh , Du Shuyan , Palmer Scott M. , Karsdal Morten , Luo Yi , Minnich Anne 
Published: March 2022

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with limited treatment options. A phase 2 trial (NCT01766817) showed that twice-daily treatment with BMS-986020, a lysophosphatidic acid receptor 1 (LPA1) antagonist, significantly decreased the slope of forced vital capacity (FVC) decline over 26 weeks compared with placebo in patients with IPF. This analysis aimed to better understand the impact of LPA1antagonism on extracellular matrix (ECM)-neoepitope biomarkers and lung function through a post hoc analysis of the phase 2 study, along with an in vitro fibrogenesis model.MethodsSerum levels of nine ECM-neoepitope biomarkers were measured in patients with IPF. The association of biomarkers with baseline and change from baseline FVC and quantitative lung fibrosis as measured with high-resolution computed tomography, and differences between treatment arms using linear mixed models, were assessed. The Scar-in-a-Jar in vitro fibrogenesis model was used to further elucidate the antifibrotic mechanism of BMS-986020.ResultsIn 140 patients with IPF, baseline ECM-neoepitope biomarker levels did not predict FVC progression but was significantly correlated with baseline FVC and lung fibrosis measurements. Most serum ECM-neoepitope biomarker levels were significantly reduced following BMS-986020 treatment compared with placebo, and several of the reductions correlated with FVC and/or lung fibrosis improvement. In the Scar-in-a-Jar in vitro model, BMS-986020 potently inhibited LPA1-induced fibrogenesis.ConclusionsBMS-986020 reduced serum ECM-neoepitope biomarkers, which were previously associated with IPF prognosis. In vitro, LPA promoted fibrogenesis, which was LPA1 dependent and inhibited by BMS-986020. Together these data elucidate a novel antifibrotic mechanism of action for pharmacological LPA1blockade.Trial registrationClinicalTrials.gov identifier: NCT01766817; First posted: January 11, 2013;https://clinicaltrials.gov/ct2/show/NCT01766817.
Placing equity at the heart of eHealth implementation: a qualitative pilot study
Authors: Heinsch Milena , Tickner Campbell , Kay-Lambkin Frances 
Published: March 2022

Abstract
Background
There is a growing urgency to tackle issues of equity and justice in the implementation of eHealth technologies.

Methods
Qualitative interviews were conducted with 19 multidisciplinary health professionals to explore the implementation and uptake of eHealth technologies in practice. The aim of this article was to examine in more detail issues of equity and justice in the implementation and uptake of eHealth technologies in practice. Results were analysed using Braun and Clarke’s six-step reflexive thematic analysis approach.

Results
Nancy Fraser’s concept of social justice is introduced as a novel framework for inquiry into the implementation of digital health services. Health professionals reported that eHealth offered their clients a greater sense of safety, convenience, and flexibility, allowing them to determine the nature and pace of their healthcare, and giving them more control over their treatment and recovery. However, they also expressed concerns about the use of eHealth with clients whose home environment is unsafe. Application of Fraser’s framework revealed that eHealth technologies may not always provide a secure clinical space in which the voices of vulnerable clients can be recognised and heard. It also highlighted critical systemic and cultural barriers that hinder the representation of clients’ voices in the decision to use eHealth technologies and perpetuate inequalities in the distribution of eHealth services.

Conclusions
To facilitate broad participation, eHealth tools need to be adaptable to the needs and circumstances of diverse groups. Future implementation science efforts must also be directed at identifying and addressing the underlying structures that hinder equitable recognition, representation, and distribution in the implementation of eHealth resources.
Monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) and the risk of all-cause and cardiovascular mortality: a nationwide cohort study in the United States
Authors: Jiang Ming , Yang Jiaming , Zou Huayiyang , Li Menghuan , Sun Wei , Kong Xiangqing 
Published: March 2022

Abstract
Background
Elevated monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is relevant to higher all-cause and cardiovascular mortality in patients with coronary artery disease and other comorbidities. However, the predictive values of MHR for mortality in the general population have been underutilized. This study investigated the association of MHR with all-cause and cardiovascular mortality in the adult population of the United States.

Methods
This study included 34,335 participants (≥20 years) from the National Health and Nutrition Examination Survey 1999–2014 that were grouped according to MHR tertiles. Kaplan-Meier plots and long-rank tests were employed to investigate differences in survival among the groups. Moreover, the relationship of MHR with all-cause and cardiovascular mortality was further explored using multivariate Cox regression and restricted cubic spline analysis.

Results
During the average follow-up of 93.5 ± 56 months, 4310 (12.6%) participants died, with 754 (2.2%) deaths attributed to cardiovascular diseases. Kaplan-Meier analysis revealed statistically obvious differences in all-cause and cardiovascular mortality among the MHR tertiles (log-rank test: all P < 0.001). In multi-adjusted models, participants in the highest tertile of MHR had an increased risk of all-cause (hazard ratio [HR] = 1.19, 95% confidence interval [CI] 1.10–1.29) and cardiovascular mortality (HR = 1.44, 95% CI 1.17–1.77), compared to those in the lowest tertile. Furthermore, the restricted cubic spline curve indicated that MHR had a non-linear association with all-cause mortality (P < 0.001), and the inflection point of MHR was 0.006. Each 2-fold change in MHR exhibited a 32% decrease (HR = 0.68, 95%CI 0.58–0.82) and a 20% increase (HR = 1.20, 95%CI 1.13–1.27) in the risk of all-cause mortality on the left and right flanks of the inflection point, respectively. Additionally, the risk of cardiovascular mortality increased by 21% per 2-fold change in MHR (HR = 1.21, 95%CI 1.07–1.36) in a linear manner.

Conclusions
MHR was significantly related to all-cause and cardiovascular mortality in the general population independent of established risk factors.
Cu-catalyzed, Mn-mediated propargylation and allenylation of aldehydes with propargyl bromides
Authors: Zhang Rongli , Xia Yanping , Yan Yuchen , Ouyang Lu 
Published: March 2022

AbstractA simple, practical, and high chemo-selective method for the synthesis of propargyl alcohol and allenyl alcohols via Cu-catalyzed, Mn-mediated propargylation and allenylation of aldehydes with propargyl bromides has been established. When 3-bromo-1-propyne was conducted under the standard condition, the aldehydes were transformed to the corresponding propargylation products completely, while when 1-bromo-2-pentyne was used, allenic alcohol was the only product. Variety of homopropargyl alcohols and allenyl alcohols were obtained in high yields and the reaction is compatible with broad substrate scopes. In addition, the large-scale reaction could also be proceeded smoothly indicating the potential synthetic applications of this transformation.Graphical Abstract
In silico evaluation of a targeted metaproteomics strategy for broad screening of cellulolytic enzyme capacities in anaerobic microbiome bioreactors
Authors: Villalobos Solis Manuel I. , Chirania Payal , Hettich Robert L. 
Published: March 2022

Abstract
Background
Microbial-driven solubilization of lignocellulosic material is a natural mechanism that is exploited in anaerobic digesters (ADs) to produce biogas and other valuable bioproducts. Glycoside hydrolases (GHs) are the main enzymes that bacterial and archaeal populations use to break down complex polysaccharides in these reactors. Methodologies for rapidly screening the physical presence and types of GHs can provide information about their functional activities as well as the taxonomical diversity within AD systems but are largely unavailable. Targeted proteomic methods could potentially be used to provide snapshots of the GHs expressed by microbial consortia in ADs, giving valuable insights into the functional lignocellulolytic degradation diversity of a community. Such observations would be essential to evaluate the hydrolytic performance of a reactor or potential issues with it.

Results
As a proof of concept, we performed an in silico selection and evaluation of groups of tryptic peptides from five important GH families derived from a dataset of 1401 metagenome-assembled genomes (MAGs) in anaerobic digesters. Following empirical rules of peptide-based targeted proteomics, we selected groups of shared peptides among proteins within a GH family while at the same time being unique compared to all other background proteins. In particular, we were able to identify a tractable unique set of peptides that were sufficient to monitor the range of GH families. While a few thousand peptides would be needed for comprehensive characterization of the main GH families, we found that at least 50% of the proteins in these families (such as the key families) could be tracked with only 200 peptides. The unique peptides selected for groups of GHs were found to be sufficient for distinguishing enzyme specificity or microbial taxonomy. These in silico results demonstrate the presence of specific unique GH peptides even in a highly diverse and complex microbiome and reveal the potential for development of targeted metaproteomic approaches in ADs or lignocellulolytic microbiomes. Such an approach could be valuable for estimating molecular-level enzymatic capabilities and responses of microbial communities to different substrates or conditions, which is a critical need in either building or utilizing constructed communities or defined cultures for bio-production.

Conclusions
This in silico study demonstrates the peptide selection strategy for quantifying relevant groups of GH proteins in a complex anaerobic microbiome and encourages the development of targeted metaproteomic approaches in fermenters. The results revealed that targeted metaproteomics could be a feasible approach for the screening of cellulolytic enzyme capacities for a range of anaerobic microbiome fermenters and thus could assist in bioreactor evaluation and optimization.
Centralized project-specific metadata platforms: toolkit provides new perspectives on open data management within multi-institution and multidisciplinary research projects
Authors: Child Andrew Wright , Hinds Jennifer , Sheneman Lucas , Buerki Sven 
Published: March 2022

AbstractOpen science and open data within scholarly research programs are growing both in popularity and by requirement from grant funding agencies and journal publishers. A central component of open data management, especially on collaborative, multidisciplinary, and multi-institutional science projects, is documentation of complete and accurate metadata, workflow, and source code in addition to access to raw data and data products to uphold FAIR (Findable, Accessible, Interoperable, Reusable) principles. Although best practice in data/metadata management is to use established internationally accepted metadata schemata, many of these standards are discipline-specific making it difficult to catalog multidisciplinary data and data products in a way that is easily findable and accessible. Consequently, scattered and incompatible metadata records create a barrier to scientific innovation, as researchers are burdened to find and link multidisciplinary datasets. One possible solution to increase data findability, accessibility, interoperability, reproducibility, and integrity within multi-institutional and interdisciplinary projects is a centralized and integrated data management platform. Overall, this type of interoperable framework supports reproducible open science and its dissemination to various stakeholders and the public in a FAIR manner by providing direct access to raw data and linking protocols, metadata and supporting workflow materials.
Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders
Authors: Lee Kevin , Jung Yewon , Vyas Yukti , Skelton Imogen , Abraham Wickliffe C. , Hsueh Yi-Ping , Montgomery Johanna M. 
Published: March 2022

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a dyad of behavioural symptoms—social and communication deficits and repetitive behaviours. Multiple aetiological genetic and environmental factors have been identified as causing or increasing the likelihood of ASD, including serum zinc deficiency. Our previous studies revealed that dietary zinc supplementation can normalise impaired social behaviours, excessive grooming, and heightened anxiety in aShank3mouse model of ASD, as well as the amelioration of synapse dysfunction. Here, we have examined the efficacy and breadth of dietary zinc supplementation as an effective therapeutic strategy utilising a non-Shank-related mouse model of ASD—mice withTbr1haploinsufficiency.MethodsWe performed behavioural assays, amygdalar slice whole-cell patch-clamp electrophysiology, and immunohistochemistry to characterise the synaptic mechanisms underlying the ASD-associated behavioural deficits observed inTbr1+/−mice and the therapeutic potential of dietary zinc supplementation. Two-way analysis of variance (ANOVA) with Šídák's post hoc test and one-way ANOVA with Tukey’s post hoc multiple comparisons were performed for statistical analysis.ResultsOur data show that dietary zinc supplementation prevents impairments in auditory fear memory and social interaction, but not social novelty, in theTbr1+/−mice.Tbr1haploinsufficiency did not induce excessive grooming nor elevate anxiety in mice. At the synaptic level, dietary zinc supplementation reversed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) andN-methyl-d-aspartate receptor (NMDAR) hypofunction and normalised presynaptic function at thalamic-lateral amygdala (LA) synapses that are crucial for auditory fear memory. In addition, the zinc supplemented diet significantly restored the synaptic puncta density of the GluN1 subunit essential for functional NMDARs as well as SHANK3 expression in both the basal and lateral amygdala (BLA) ofTbr1+/−mice.LimitationsThe therapeutic effect of dietary zinc supplementation observed in rodent models may not reproduce the same effects in human patients. The effect of dietary zinc supplementation on synaptic function in other brain structures affected byTbr1haploinsufficiency including olfactory bulb and anterior commissure will also need to be examined.ConclusionsOur data further the understanding of the molecular mechanisms underlying the effect of dietary zinc supplementation and verify the efficacy and breadth of its application as a potential treatment strategy for ASD.
Defining health data elements under the HL7 development framework for metadata management
Authors: Yang Zhe , Jiang Kun , Lou Miaomiao , Gong Yang , Zhang Lili , Liu Jing , Bao Xinyu , Liu Danhong , Yang Peng 
Published: March 2022

Abstract
Background
Health data from different specialties or domains generallly have diverse formats and meanings, which can cause semantic communication barriers when these data are exchanged among heterogeneous systems. As such, this study is intended to develop a national health concept data model (HCDM) and develop a corresponding system to facilitate healthcare data standardization and centralized metadata management.

Methods
Based on 55 data sets (4640 data items) from 7 health business domains in China, a bottom-up approach was employed to build the structure and metadata for HCDM by referencing HL7 RIM. According to ISO/IEC 11179, a top-down approach was used to develop and standardize the data elements.

Results
HCDM adopted three-level architecture of class, attribute and data type, and consisted of 6 classes and 15 sub-classes. Each class had a set of descriptive attributes and every attribute was assigned a data type. 100 initial data elements (DEs) were extracted from HCDM and 144 general DEs were derived from corresponding initial DEs. Domain DEs were transformed by specializing general DEs using 12 controlled vocabularies which developed from HL7 vocabularies and actual health demands. A model-based system was successfully established to evaluate and manage the NHDD.

Conclusions
HCDM provided a unified metadata reference for multi-source data standardization and management. This approach of defining health data elements was a feasible solution in healthcare information standardization to enable healthcare interoperability in China.
Accuracy evaluation of mainstream and sidestream end-tidal carbon dioxide monitoring during noninvasive ventilation: a randomized crossover trial (MASCAT-NIV trial)
Authors: Sakuraya Masaaki , Douno Eri , Iwata Wakana , Takaba Akihiro , Hadama Kosuke , Kawamura Natsuki , Maezawa Toshinori , Iwamoto Kei , Yoshino Yuya , Yoshida Kenichi 
Published: March 2022

Abstract
Background
The end-tidal partial pressure of carbon dioxide (PETCO2) can be used to estimate the arterial partial pressure of carbon dioxide (PaCO2) in patients who undergo mechanical ventilation via endotracheal intubation. However, no reliable method for measuring PETCO2 during noninvasive ventilation (NIV) has been established. The purpose of this study was to evaluate the correlation and agreement between PaCO2 and PETCO2 measured by these two methods and to compare them in patients who underwent NIV after extubation.

Methods
This study was a randomized, open-label, crossover trial in a mixed intensive care unit. We included patients who were planned for NIV after extubation and for whom the difference between PETCO2 and PaCO2 was ≤ 5 mmHg. We compared mainstream capnography using an inner cup via face mask (the novel method) with sidestream capnography (the previous method) during NIV. The relationships between PaCO2 and PETCO2 were evaluated by computing the Pearson correlation coefficient, and the agreement between PaCO2 and PETCO2 was estimated using the Bland–Altman method.

Results
From April 2020 to October 2021, 60 patients were included to the study. PaCO2 and PETCO2 were well correlated in both methods (the novel methods: r = 0.92, P < 0.001; the previous method: r = 0.79, P < 0.001). Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.70 (95% confidence interval [CI], 2.15–3.26) mmHg with 95% limits of agreement (LoA) ranging from − 1.61 to 7.02 mmHg, similar to the result of measurement during SBT (mean bias, 2.51; 95% CI, 2.00–3.02; 95% LoA, − 1.45 to 6.47 mmHg). In contrast, measurement using the previous method demonstrated a larger difference (mean bias, 6.22; 95% CI, 5.22–7.23; 95% LoA, − 1.54 to 13.99 mmHg).

Conclusion
The current study demonstrated that the novel PETCO2 measurement was superior to the previous method for PaCO2 prediction. During NIV, the novel method may collect as sufficient exhalation sample as during intubation. Continuous PETCO2 measurement combined with peripheral oxygen saturation monitoring is expected to be useful for early recognition of respiratory failure among high-risk patients after extubation.
Trial registration UMIN-CTR UMIN000039459. Registered February 11, 2020.
A dynamic directed transfer function for brain functional network-based feature extraction
Authors: Li Mingai , Zhang Na 
Published: March 2022

AbstractDirected transfer function (DTF) is good at characterizing the pairwise interactions from whole brain network and has been applied in discrimination of motor imagery (MI) tasks. Considering the fact that MI electroencephalogram signals are more non-stationary in frequency domain than in time domain, and the activated intensities of α band (8–13 Hz) and β band [13–30 Hz, with $$\beta_{1}$$

β
1

(13–21 Hz) and $$\beta_{2}$$

β
2

(21–30 Hz) included] have considerable differences for different subjects, a dynamic DTF (DDTF) with variable model order and frequency band is proposed to construct the brain functional networks (BFNs), whose information flows and outflows are further calculated as network features and evaluated by support vector machine. Extensive experiments are conducted based on a public BCI competition dataset and a real-world dataset, the highest recognition rate achieve 100% and 86%, respectively. The experimental results suggest that DDTF can reflect the dynamic evolution of BFN, the best subject-based DDTF appears in one of four frequency sub-bands (α, β, $$\beta_{1} ,$$

β
1

,

$${ }\beta_{2}$$

β
2

) for discrimination of MI tasks and is much more related to the current and previous states. Besides, DDTF is superior compared to granger causality-based and traditional feature extraction methods, the t-test and Kappa values show its statistical significance and high consistency as well.
Microfluidics-based strategies for molecular diagnostics of infectious diseases
Authors: Wang Xin , Hong Xian-Zhe , Li Yi-Wei , Li Ying , Wang Jie , Chen Peng , Liu Bi-Feng 
Published: March 2022

AbstractTraditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology, are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses. Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection. This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes, including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.