bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese scientists’ awareness of, attitudes to and involvement in open-access publishing
Authors: Lu Yangxu , Zhao Yandong , Huang Lei
Published: March 2022

‘Open access’ is an important part of the open science movement and a significant change to the existing model of academic publication. Based on data from a large-scale survey of Chinese scientists, this paper describes their awareness of, attitudes to and involvement in open access. Policy recommendations on promoting open access in China are proposed at the end of the paper.
The Use of Cognitive Diagnostic Modeling in the Assessment of Computational Thinking
Authors: Li Tingxuan , Traynor Anne
Published: March 2022

Computational thinking (CT) is a set of cognitive skills that every child should acquire. K–12 classrooms are expected to provide students opportunities (tasks) to think computationally. We introduce a CT competency assessment for middle school students. The assessment design process started by establishing a cognitive model of CT domain mastery, in which three broad skill types were identified to represent CT competency. After multiple-choice item prototypes were written, pilot tested, and revised, 15 of them were finally selected to be administered to 564 students in two middle schools in the Midwestern United States. Using a cognitive diagnostic scoring model, mastery classifications for each student were determined that can be used diagnostically by teachers as a pretest and, perhaps in the future, to compare the outcomes of CT instructional programs. The results inform an initial understanding of typical learning progressions in CT at the middle school level.
The Patterns of Adolescents’ Math and Science Motivational Beliefs: Examining Within–Racial/Ethnic Group Changes and Their Relations to STEM Outcomes
Authors: Hsieh Ta-yang , Simpkins Sandra D.
Published: March 2022

The racial/ethnic disparities and average declines in science, technology, engineering, and mathematics (STEM) motivation during adolescence are worrisome. Although STEM motivational beliefs are theorized to function in conjunction with one another, the unique patterns and how they change over time for different racial/ethnic groups remain understudied. Using data from the High School Longitudinal Study ( N = 18,260), we identified four and five patterns of math and science motivational beliefs in 9th and 11th grade, respectively, and examined their prevalence among Asian, Black, Latina/o, White, and Multiracial adolescents. We found patterns with overall high/low beliefs, patterns with varying levels of motivational beliefs, and patterns characterized by domain differentiation. Then, we charted the stability and changes in those patterns from 9th to 11th grade for each racial/ethnic group and how the patterns at 11th grade were associated with adolescents’ STEM career expectations and high school math and science grade point averages.
Dual Caregivers of Persons living with Dementia: The Added Stress of COVID-19 Pandemic
Authors: Atkinson Emily , Savla Jyoti , Roberto Karen A. , Blieszner Rosemary , McCann Brandy R. , Knight Aubrey L.
Published: March 2022

Serving in dual caregiving roles presents challenges and has consequences for caregivers’ physical and mental health. Forty-six dual caregivers in rural southwest Virginia participated in one semi-structured telephone interview pre-pandemic. Of these caregivers, nine dual caregivers of multiple older adults (MOA) and six caregivers of multiple generations (MG) participated in two telephone interviews during the COVID-19 pandemic. Pre-pandemic health, stress, and support data were used to compare dual caregivers of MOA and MG; differences were minimal. Responses to interviews conducted during the pandemic highlighted the effects of social restrictions on MOA and MG caregivers, revealing five themes (1) Increased isolation, (2) Increased need for vigilance, (3) Negative impact on mental health, (4) Tendency to “do it all,” and (5) Increased informal help. MOA and MG caregivers differed on managing care responsibilities and ensuring the health of care recipients. In general, dual caregivers experienced decreased mental health, increased social isolation, and increased caregiving responsibilities. Antecedents of the pandemic experiences differentiated MOA and MG caregiver. Findings suggest that programs and services should target dual caregivers’ unique needs.
Visual perceptual salience and novel referent selection in children with and without autism spectrum disorder
Authors: Venker Courtney E. , Neumann Dominik , Aladé Fashina
Published: March 2022

Background & Aims

Many young children with autism spectrum disorder (ASD) demonstrate striking delays in early vocabulary development. Experimental studies that teach the meanings of novel nonwords can determine the effects of linguistic and attentional factors. One factor that may affect novel referent selection in children with ASD is visual perceptual salience—how interesting (i.e., striking) stimuli are on the basis of their visual properties. The goal of the current study was to determine how the perceptual salience of objects affected novel referent selection in children with ASD and children who are typically developing (TD) of similar ages (mean age 3–4 years).

Methods

Using a screen-based experimental paradigm, children were taught the names of four unfamiliar objects: two high-salience objects and two low-salience objects. Their comprehension of the novel words was assessed in low-difficulty and high-difficulty trials. Gaze location was determined from video by trained research assistants.

Results

Contrary to initial predictions, findings indicated that high perceptual salience disrupted novel referent selection in the children with ASD but facilitated attention to the target object in age-matched TD peers. The children with ASD showed no significant evidence of successful novel referent selection in the high-difficulty trials. Exploratory reaction time analyses suggested that the children with autism showed “stickier” attention—had more difficulty disengaging (i.e., looking away)—from high-salience distracter images than low-salience distracter images, even though the two images were balanced in salience for any given test trial.

Conclusions and Clinical Implications

These findings add to growing evidence that high perceptual salience has the potential to disrupt novel referent selection in children with ASD. These results underscore the complexity of novel referent selection and highlight the importance of taking the immediate testing context into account. In particular, it is important to acknowledge that screen-based assessments and screen-based learning activities used with children with ASD are not immune to the effects of lower level visual features, such as perceptual salience.
MAGE genes encoding for embryonic development in cattle is mainly regulated by zinc finger transcription factor family and slightly by CpG Islands
Authors: Abera Bosenu , Dinka Hunduma
Published: March 2022

Background

Melanoma Antigen Genes (MAGEs) are a family of genes that have piqued the interest of scientists for their unique expression pattern. The MAGE genes can be classified into type I MAGEs that expressed in testis and other reproductive tissues while type II MAGEs that have broad expression in many tissues. Several MAGE gene families are expressed in embryonic tissues in almost all eukaryotes, which is essential for embryo development mainly during germ cell differentiation. The aim of this study was to analyze the promoter regions and regulatory elements (transcription factors and CpG islands) of MAGE genes encoding for embryonic development in cattle.

Results

The in silico analysis revealed the highest promoter prediction scores (1.0) for TSS were obtained for two gene sequences (MAGE B4-like and MAGE-L2) while the lowest promoter prediction scores (0.8) was obtained for MAGE B17-like. It also revealed that the best common motif, motif IV, bear a resemblance with three TF families including Zinc-finger family, SMAD family and E2A related factors. From thirteen identified TFs candidates, majority of them (11/13) were clustered to Zinc-finger family serving as transcriptionally activator role whereas three (SP1, SP3 and Znf423) of them as activator or repressor in response to physiological and pathological stimuli. On the other hand we revealed slightly rich CpG islands in the gene body and promoter regions of MAGE genes encoding for embryonic development in cattle.

Conclusion

This in silico analysis of gene promoter regions and regulatory elements in MAGE genes could be useful for understanding regulatory networks and gene expression patterns during embryo development in bovine.
MELD-XI score predict no-reflow phenomenon and short-term mortality in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Zhang Xin-Tao , Lin Zhao-Rong , Zhang Lin , Zhao Zi-Wen , Chen Liang-Long
Published: March 2022

Introduction

No-reflow phenomenon (NRP) is one of the complications that mostly occur during percutaneous coronary intervention (PCI). In this study, we comprehensively examined the relationship between the model for end-stage liver disease-XI (MELD-XI) score and NRP. Moreover, we discussed whether the MELD-XI score could be considered as an accurate risk assessment score of patients with ST-segment elevation myocardial infarction (STEMI) who are candidates for PCI.

Methods

This retrospective study involved 693 patients with acute STEMI and who underwent an emergency PCI. They were divided into a normal reflow group or a no-reflow group on the basis of the flow rate of post-interventional thrombolysis in myocardial infarction. Univariate, multivariate logistic regression, and Cox regression analyses were performed to identify the independent predictors of NRP in both groups. Receiver operator characteristic (ROC) curves and Kaplan–Meier curves were plotted to estimate the predictive values of the MELD-XI score.

Results

MELD-XI score was found to be an independent indicator of NRP (odds ratio: 1.247, 95% CI: 1.144–1.360, P < 0.001). Multivariate Cox regression analysis also revealed that the MELD-XI score is an independent prognostic factor for 30-day all-cause mortality (hazard ratio: 1.155, 95% CI: 1.077–1.239, P < 0.001). Moreover, according to the ROC curves, the cutoff value of the MELD-XI score to predict NRP was 9.47 (area under ROC curve: 0.739, P < 0.001). The Kaplan–Meier curves for 30-day all-cause mortality revealed lower survival rate in the group with a MELD-XI score of > 9.78 (P < 0.001).

Conclusion

The MELD-XI score can be used to predict NRP and the 30-day prognosis in patients with STEMI who are candidates for primary PCI. It could be adopted as an inexpensive and a readily available tool for risk stratification.
Ripple effects mapping: capturing the wider impacts of systems change efforts in public health
Authors: Nobles James , Wheeler Jessica , Dunleavy-Harris Kirsty , Holmes Richard , Inman-Ward Alan , Potts Alexandra , Hall Jennifer , Redwood Sabi , Jago Russell , Foster Charlie
Published: March 2022

Background

Systems approaches are currently being advocated and implemented to address complex challenges in Public Health. These approaches work by bringing multi-sectoral stakeholders together to develop a collective understanding of the system, and then to identify places where they can leverage change across the system. Systems approaches are unpredictable, where cause-and-effect cannot always be disentangled, and unintended consequences – positive and negative – frequently arise. Evaluating such approaches is difficult and new methods are warranted.

Methods

Ripple Effects Mapping (REM) is a qualitative method which can capture the wider impacts, and adaptive nature, of a systems approach. Using a case study example from the evaluation of a physical activity-orientated systems approach in Gloucestershire, we: a) introduce the adapted REM method; b) describe how REM was applied in the example; c) explain how REM outputs were analysed; d) provide examples of how REM outputs were used; and e) describe the strengths, limitations, and future uses of REM based on our reflections.

Results

Ripple Effects Mapping is a participatory method that requires the active input of programme stakeholders in data gathering workshops. It produces visual outputs (i.e., maps) of the programme activities and impacts, which are mapped along a timeline to understand the temporal dimension of systems change efforts. The REM outputs from our example were created over several iterations, with data collected every 3–4 months, to build a picture of activities and impacts that have continued or ceased. Workshops took place both in person and online. An inductive content analysis was undertaken to describe and quantify the patterns within the REM outputs. Detailed guidance related to the preparation, delivery, and analysis of REM are included in this paper.

Conclusion

REM may help to advance our understanding and evaluation of complex systems approaches, especially within the field of Public Health. We therefore invite other researchers, practitioners and policymakers to use REM and continuously evolve the method to enhance its application and practical utility.
Osteoclasts differential-related prognostic biomarker for osteosarcoma based on single cell, bulk cell and gene expression datasets
Authors: Shao Haiyu , Ge Meng , Zhang Jun , Zhao Tingxiao , Zhang Shuijun
Published: March 2022

Osteosarcoma (OS) is one of the most common primary bone malignant tumors. Osteoclasts have been shown to have a valuable role in OS. In the present study, we analyzed the differentiation states of osteoclasts in OS and their prognostic significance based on integrated scRNA-seq and bulk RNA-seq data. Osteoclasts in distinct differentiation states were characterized, and 661 osteoclasts differentiation-related genes (ODRGs) were obtained. ORDGs in distinct differentiation states were enriched in distinct functions and pathways. TPM1, S100A13, LOXL1, PSMD10, ST3GAL4, PEF1, SERPINE2, TUBB, FAM207A, TUBA1A, and DCN were identified as the significant survival-predicting ODRGs. We successfully developed a risk score model based on these survival-predicting ODRGs. In addition, we generated a nomogram applicable for clinical with both ODRGs signatures and clinicopathological parameters, and validated in OS cohorts to predict OS patient outcome. This study proposed and verified the important roles of osteoclasts differentiation in the prognosis of patients with OS, suggesting promising therapeutic targets for OS.
Log odds of positive lymph nodes as a novel prognostic predictor for colorectal cancer: a systematic review and meta-analysis
Authors: Li Yiding , Wu Guiling , Zhang Yujie , Han Ben , Yang Wanli , Wang Xiaoqian , Duan Lili , Niu Liaoran , Chen Junfeng , Zhou Wei , Liu Jinqiang , Fan Daiming , Hong Liu
Published: March 2022

Background

Colorectal cancer (CRC) is the third most prevalent cancer in the world, which remains one of the leading causes of cancer-related deaths. Accurate prognosis prediction of CRC is pivotal to reduce the mortality and disease burden. Lymph node (LN) metastasis is one of the most commonly used criteria to predict prognosis in CRC patients. However, inaccurate surgical dissection and pathological evaluation may lead to inaccurate nodal staging, affecting the effectiveness of pathological N (pN) classification in survival prediction among patients with CRC. In this meta-analysis, we aimed to estimate the prognostic value of the log odds of positive lymph nodes (LODDS) in patients with CRC.

Methods

PubMed, Medline, Embase, Web of Science and the Cochrane Library were systematically searched for relevant studies from inception to July 3, 2021.

Statistical analyses were performed on Stata statistical software Version 16.0 software. To statistically assess the prognostic effects of LODDS, we extracted the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and disease-free survival (DFS) from the included studies.

Results

Ten eligible articles published in English involving 3523 cases were analyzed in this study. The results showed that LODDS1 and LODDS2 in CRC patients was correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.77, 95% CI (1.38, 2.28); LODDS2 vs. LODDS0: HR = 3.49, 95% CI (2.88, 4.23)). Meanwhile, LODDS1 and LODDS2 in CRC patients was correlated with poor DFS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.82, 95% CI (1.23, 2.68); LODDS2 vs. LODDS0: HR =3.30, 95% CI (1.74, 6.27)).

Conclusions

The results demonstrated that the LODDS stage was associated with prognosis of CRC patients and could accurately predict the prognosis of patients with CRC.
Sequential changes in intraocular pressure during strabismus surgery in patients with thyroid eye disease
Authors: Jeong Areum , Kim Won Jae
Published: March 2022

Background/Aims

To investigate the sequential change in intraocular pressure (IOP) during strabismus surgery in patients with thyroid eye disease (TED).

Methods

This prospective study included patients with TED who underwent strabismus surgery (medial rectus [MR], inferior rectus [IR], and superior rectus [SR] recession) between March 2018 and December 2020. The IOP was measured six times during surgery (5 min after intubation, after isolation of the muscle using a hook and dissection of the surrounding tissue, immediately before muscle detachment, immediately after muscle detachment, after reattachment of the muscle, and after closure of the conjunctiva).

Results

Thirty-five eyes of 18 patients were included. The mean IOP at first was 21.1 mmHg, which significantly increased to 28.6 mmHg after muscle isolation. The IOP significantly decreased to 15.5 mmHg after muscle detachment. This increased to 19.1 mmHg after muscle reattachment. The last IOP was 18.9 mmHg. There were similar patterns of sequential change in the IOP among the three muscles. The MR showed the highest increase in IOP. The IR showed the lowest mean IOP compared with the other two muscles.

Conclusions

The IOP was elevated during the isolation and dissection of the surrounding muscle tissue, especially in the MR. The IOP significantly decreased after muscle detachment and was maintained until the last measurement, even after muscle reattachment. IR showed the lowest IOP among the three muscles during surgery.
Public knowledge, attitude, and acceptance toward COVID-19 vaccines in Palestine: a cross-sectional study
Authors: Al-kafarna Mohammed , Matar Sajeda Ghassan , Almadhoon Hossam Waleed , Almaghary Bashar Khaled , Zaazouee Mohamed Sayed , Elrashedy Asmaa Ahmed , Wafi Dalia Sami , Jabari Sami D. , Salloum Omar H. , Ibrahim Eman Ahmed , Alagha Hala ZI , Hasabo Elfatih A. ,   IMedRA Collaboration Team, AL-Ali Thara Kh. Hussein , Neiroukh Haroun , Almakhtoob Falasteen Jameel , Marabeh Sireen Sufian , Badawi Malak Y. , Jabari Anwar Y. , Al-Ali Fida Hussien , Asafrah Tamer Sami , Muhanna Yara Safwat
Published: March 2022

Background

The consequences of the COVID-19 pandemic on physical and mental health in addition to the global economy are huge. Vaccination is a pivotal measure to decrease COVID-19 morbidity and mortality and to help bring the pandemic under control. Yet, success of the vaccination process depends on the population’s willingness to be vaccinated which may be determined by their level of knowledge about and trust in currently available COVID-19 vaccines. Therefore, this study aims to assess the knowledge, attitude, and acceptance of Palestinians towards COVID-19 vaccines.

Methods

A national cross-sectional study was distributed in different Palestinian regions to assess the knowledge and attitude of Palestinians toward COVID-19 vaccines using an online questionnaire, it included three sections; sociodemographic characteristics, knowledge assessment questions, and attitude assessment questions.

Results

A total of 6226 participants completed the questionnaire; among them, 41.36% believed that vaccines are safe, 69.02% agreed that vaccines are vital to protect from COVID-19; in addition, 55.1% approve administering the vaccine once available, and 37.86% do not believe their benefits outweigh the risks. The Source of information for 22.07% of participants in social media, while 11.92% rely on health care providers. Participants’ attitudes and knowledge were significantly affected by gender, governorate, age, education level, and marital status (P <0.001).

Conclusion

The findings suggest that there is good knowledge and attitude toward the vaccination process against COVID-19 in Palestine, although low acceptance was detected. Awareness campaigns are required to spread reliable knowledge about COVID-19 vaccines.
Public perception of isolation, quarantine, social distancing and community containment during COVID-19 pandemic
Authors: Hussain Tahreem , Jawed Nida , Mughal Saba , Shafique Kashif
Published: March 2022

Background

Effective strategies of prevention have been and can aid in reducing and overcoming contagious diseases including COVID-19, still there is dearth of knowledge regarding general public awareness and perception. The current study aims to determine the existing knowledge and perception of people living in Karachi about isolation, quarantine, social distancing and community containment.

Methods

This cross-sectional online survey was conducted during the months of March and April 2020. The study included men and women of age 18 years and above quarantined during COVID-19. Convenience sampling followed by snowball sampling technique was used. An online structured questionnaire was developed using Google Form. It included questions on socio demographic information, public knowledge and perception about isolation, quarantine, social distancing and community containment. Chi-square test was used for categorical variables and p value of < 0.05 was considered statistically significant.

Results

A total of 548 participants were involved in this survey, 34% (n = 184) males with a mean age of 28 ± 10 years ranging from 18 to 75 years. The major source of hearing about COVID-19 was social media (72%, n = 393). Overall knowledge scores revealed that 27% (n = 146) participants had excellent knowledge about symptoms and prevention of the COVID-19. Excellent knowledge of quarantining, isolation and community containment and social distancing was 38% among participants. Participants who had good and excellent knowledge were more likely to have positive perception of isolation (p-value < 0.001). Majority participants (89%, n = 487) felt isolation may or may not be against human rights and this perception was found significantly associated with moderate to excellent knowledge about community mitigation measures (p-value = 0.009).

Conclusion

This study concludes that optimal public knowledge and perception related to certain aspects of isolation, quarantine, social distancing and community containment exists however knowledge gaps and misperceptions prevail that need to be addressed.
Optimizing the integration of family caregivers in the delivery of person-centered care: evaluation of an educational program for the healthcare workforce
Authors: Parmar Jasneet K. , L’Heureux Tanya , Anderson Sharon , Duggleby Wendy , Pollard Cheryl , Poole Lisa , Charles Lesley , Sonnenberg Lyn K. , Leslie Myles , McGhan Gwen , Huhn Arlene , Sereda Sandy , Marion Cecilia , Tarnowski Glenda , Mah Jennifer , Melenberg Denise , Weir Carolyn , Pooler Charlotte , MacLachlan Nora , Bremault-Phillips Suzette , Tian Peter George J. , Sacrey Lori-Ann R.
Published: March 2022

Background

While family caregivers provide 70-90% of care for people living in the community and assist with 10-30% of the care in congregate living, most healthcare providers do not meaningfully involve family caregivers as partners in care. Recent research recommends that the healthcare workforce receive competency-based education to identify, assess, support, and partner with family caregivers across the care trajectory.

Objective

This paper reports a mixed-methods evaluation of a person-centered competency-based education program on Caregiver-Centered Care for the healthcare workforce.

Methods

This foundational education was designed for all healthcare providers and trainees who work with family caregivers and is offered free online (caregivercare.ca). Healthcare providers from five healthcare settings (primary, acute, home, supportive living, long-term care) and trainees in medicine, nursing, and allied health were recruited via email and social media. We used the Kirkpatrick-Barr health workforce training evaluation framework to evaluate the education program, measuring various healthcare providers’ learner satisfaction with the content (Level 1), pre-post changes in knowledge and confidence when working with family caregivers (Level 2), and changes in behaviors in practice (Level 3).

Results

Participants were primarily healthcare employees (68.9%) and trainees (21.7%) and represented 5 healthcare settings. Evaluation of the first 161 learners completing the program indicated that on a 5-point Likert scale, the majority were satisfied with the overall quality of the education (Mean(M) = 4.69; SD = .60). Paired T-tests indicated that out of a score of 50, post-education changes in knowledge and confidence to work with family caregivers was significantly higher than pre-education scores (pre M = 38.90, SD = 6.90; post M = 46.60, SD = 4.10; t(150) = − 16.75, p < .0001). Qualitative results derived from open responses echoed the quantitative findings in satisfaction with the education delivery as well as improvements in learners’ knowledge and confidence.

Conclusion

Health workforce education to provide person-centered care to all family caregivers is an innovative approach to addressing the current inconsistent system of supports for family caregivers. The education program evaluated here was effective at increasing self-reported knowledge and confidence to work with family caregivers.
Do characteristics of family members influence older persons’ transition to long-term healthcare services?
Authors: Syse Astri , Artamonova Alyona , Thomas Michael , Veenstra Marijke
Published: March 2022

Background

Future demographic and economic changes warrant a better understanding of older persons’ need for health-related long-term care services (LTC). LTC uptake among older people is likely to be influenced by the presence or absence of family members, but there is scarce research on the role played by partners with different caregiving potential. There is even less research on the contributions of adult children and their caregiving potential. The current study examines the extent to which transitions into LTC in older men and women differ according to the presence and caregiving potential of partners and children.

Methods

Linked registry data for Norway on older persons (aged 65+), their partners, and their adult children are used to examine how characteristics of these family members influence transitions into LTC from 2010 to 2016, using logistic discrete-time hazard regression models. We observed around 215,000 transitions to LTC, corresponding to around 26.3% of individuals and 5.4% of the total person-years (4.0 million). Caregiving potential is measured in terms of employment, income, health and educational attainment for partners and education and geographical proximity for children.

Results

Personal, partner and child(ren)’s resources are all associated with older persons’ LTC uptake. Unpartnered and/or childless older people are more likely to use LTC than those with partners and/or child(ren). Older persons with resourceful partners and children are the least likely to transition into LTC. The geographical proximity of adult children appears to have only a minor influence on LTC use among older people.

Conclusions

Population ageing and strained public resources will likely challenge the future provision of formal old-age care. The role of family networks in the future provision of formal old-age care is expected to become progressively important in the years to come. Inequalities in the health, care and welfare of older persons with and without resourceful family members are likely to increase.
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

Background

Idiopathic 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.

Methods

Serum 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.

Results

In 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.

Conclusions

BMS-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

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

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

A 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

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

Open 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

Background

Autism 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.

Methods

We 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.

Results

Our 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.

Limitations

The 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.

Conclusions

Our 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

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

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.