bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell RNA Sequencing Reveals Endothelial Cell Transcriptome Heterogeneity Under Homeostatic Laminar Flow
Authors: Liu Ziqing , Ruter Dana L. , Quigley Kaitlyn , Tanke Natalie T. , Jiang Yuchao , Bautch Victoria L. 
Published: August 2021

Objective:
Endothelial cells (ECs) that form the innermost layer of all vessels exhibit heterogeneous cell behaviors and responses to pro-angiogenic signals that are critical for vascular sprouting and angiogenesis. Once vessels form, remodeling and blood flow lead to EC quiescence, and homogeneity in cell behaviors and signaling responses. These changes are important for the function of mature vessels, but whether and at what level ECs regulate overall expression heterogeneity during this transition is poorly understood. Here, we profiled EC transcriptomic heterogeneity, and expression heterogeneity of selected proteins, under homeostatic laminar flow.

Approach and Results:
Single-cell RNA sequencing and fluorescence microscopy were used to characterize heterogeneity in RNA and protein gene expression levels of human ECs under homeostatic laminar flow compared to nonflow conditions. Analysis of transcriptome variance, Gini coefficient, and coefficient of variation showed that more genes increased RNA heterogeneity under laminar flow relative to genes whose expression became more homogeneous, although small subsets of cells did not follow this pattern. Analysis of a subset of genes for relative protein expression revealed little congruence between RNA and protein heterogeneity changes under flow. In contrast, the magnitude of expression level changes in RNA and protein was more coordinated among ECs in flow versus nonflow conditions.

Conclusions:
ECs exposed to homeostatic laminar flow showed overall increased heterogeneity in RNA expression levels, while expression heterogeneity of selected cognate proteins did not follow RNA heterogeneity changes closely. These findings suggest that EC homeostasis is imposed post-transcriptionally in response to laminar flow.
Real-World Experience With the SAPIEN 3 Ultra Transcatheter Heart Valve: A Propensity-Matched Analysis From the United States
Authors: Nazif Tamim M. , Cahill Thomas J. , Daniels David , McCabe James M. , Reisman Mark , Chakravarty Tarun , Makkar Raj , Krishnaswamy Amar , Kapadia Samir , Chehab Bassem M. , Wang John , Spies Christian , Rodriguez Evelio , Kaneko Tsuyoshi , Hahn Rebecca T. , Leon Martin B. , George Isaac 
Published: August 2021

Background:
Paravalvular regurgitation (PVR) after transcatheter aortic valve replacement is associated with adverse clinical outcomes. The SAPIEN 3 Ultra (Ultra) is a new generation balloon-expandable transcatheter heart valve with a modified external skirt that is designed to reduce PVR, but reports of clinical and echocardiographic outcomes are limited. The aim of this study was to compare short-term outcomes of patients undergoing transcatheter aortic valve replacement with the Ultra and the original SAPIEN 3 (S3) transcatheter heart valve in a large national registry.

Methods:
Data from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was used to compare patients who underwent elective, transfemoral transcatheter aortic valve replacement with the Ultra or S3 transcatheter heart valve. Clinical and echocardiographic outcomes were analyzed in a propensity-matched cohort at discharge and 30 days.

Results:

Patients who underwent transcatheter aortic valve replacement with Ultra (N=1324) from January 2019 to February 2020 were propensity score–matched with patients treated with S3 (N=32 982) during the same period, resulting in 1324 matched pairs. There was no difference in the rate of device success between patients treated with Ultra and S3 (97.1% versus 98.0%,
P
=0.11). At hospital discharge, PVR was significantly reduced with Ultra compared with S3, with mild PVR in 9.0% versus 13.9% and moderate or greater PVR in 0.1% versus 0.4% (overall
P
<0.01). At 30 days, there were no differences between Ultra and S3 recipients in the rates of all-cause mortality or stroke (1.8% versus 2.8%,
P
=0.10), major vascular complications (1.1% versus 1.0%,
P
=0.84), or permanent pacemaker implantation (6.4% versus 6.2%,
P
=0.81).

Conclusions:
In this propensity-matched analysis from the Transcatheter Valve Therapy Registry, the Ultra transcatheter heart valve was associated with similar procedural and 30-day clinical outcomes, but reduced incidence of PVR, compared with S3. The clinical benefit of less PVR should be evaluated in longer-term studies.
A Prayer Book for the Twenty-first Century?
Authors: Burns Stephen , Cones Bryan 
Published: August 2021

In the more than thirty years that have passed since the authorization of the 1979 Book of Common Prayer, scholars and practitioners of its liturgical vision have mined the riches of its “baptismal ecclesiology,” its variety of texts, and its permissive rubrics; they have also raised new questions about its inconsistencies and shortcomings. Anglican and ecumenical partner churches have adapted and improved upon material found in the BCP in their own new liturgical resources, suggesting directions for further liturgical renewal, and the Episcopal Church itself has authorized supplemental texts in its Enriching Our Worship series, which began publication in 1998. Questions concerning expansive language, the relationship between baptismal ministry and its expression in holy orders, and the contextualization of liturgy in a multicultural church have come to the fore as primary concerns of the church in the twenty-first century, with important implications for the celebration of liturgy. The authors contend that attention to these questions, particularly regarding the language of prayer and the relationships among the ministers within the assembly, requires a more comprehensive discussion of liturgical renewal in the church, including the revision of the Book of Common Prayer itself. “… may be altered, abridged, enlarged, amended, or otherwise disposed of …”1
Head Scanning Behavior Predicts Hazard Detection Safety Before Entering an Intersection
Authors: Savage Steven W. , Zhang Lily , Swan Garrett , Bowers Alex R. 
Published: August 2021

Objective We conducted a driving simulator study to investigate scanning and hazard detection before entering an intersection. Background Insufficient scanning has been suggested as a factor contributing to intersection crashes. However, little is known about the relative importance of the head and eye movement components of that scanning in peripheral hazard detection. Methods Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. They completed two city drives (42 intersections per drive) with motorcycle hazards appearing at 16 four-way intersections per drive. Results Older subjects missed more hazards (10.2% vs. 5.2%). Failing to make a scan with a substantial head movement was the primary reason for missed hazards. When hazards were detected, older drivers had longer RTs (2.6s vs. 2.3s), but drove more slowly; thus, safe response rates did not differ between the two groups (older 83%; younger 82%). Safe responses were associated with larger (28.8° vs. 20.6°) and more numerous (9.4 vs. 6.6) gaze scans. Scans containing a head movement were stronger predictors of safe responses than scans containing only eye movements. Conclusion Our results highlight the importance of making large scans with a substantial head movement before entering an intersection. Eye-only scans played little role in detection and safe responses to peripheral hazards. Application Driver training programs should address the importance of making large scans with a substantial head movement before entering an intersection.
Opinion on Maintaining In-House GLP Status for Toxicologic Pathology in Pharmaceutical and (Agro)Chemical Development
Authors: Gauthier Béatrice E. , Bach Ute , Chanut Franck , De Jonghe Sandra , Groeters Sibylle , Mueller Gundi , Palazzi Xavier , Pohlmeyer-Esch Gabriele , Rinke Matthias , Schorsch Frédéric 
Published: August 2021

Many pharmaceutical companies have recently elected to stop maintaining good laboratory practices (GLP) status of their R&D sites. Similar discussions have also been engaged in the (agro)chemical industry. This opinion paper examines the pros and cons of maintaining facility GLP status for the purposes of performing the pathology interpretation or peer reviews of GLP studies internally. The toxicologic pathologist provides gross and histomorphologic evaluation and interpretation of nonclinical exploratory and regulatory studies during drug and (agro)chemical development. This assessment significantly contributes to human risk assessment by characterizing the toxicological profile and discussing the human relevance of the findings. The toxicologic pathologist is a key contributor to compound development decisions (advancement or termination) and in the development of de-risking strategies for backup compounds, thus playing a critical role in helping to reduce the late attrition of drugs and chemicals. Maintaining GLP compliance is often perceived as a costly and cumbersome process; a common and short-term strategy to reduce the costs is to outsource regulatory toxicity studies. However, there are significant advantages in maintaining the GLP status for toxicologic pathology activities in-house including the sustainable retention of internal pathology expertise that has maintained the necessary training needed to manage GLP studies. [Box: see text]
Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation
Authors: Qiao Lin , Yang Yuting , Yue Dongmei 
Published: August 2021

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.
Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis
Authors: Wang Yin , Li Yanqing , Chai Ye 
Published: August 2021

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.
Association between pain and gait instability in patients with lumbar disc herniation
Authors: Lee Keunjae , Kim Eun-San , Jung Boyoung , Park Sang-Won , Ha In-Hyuk 
Published: August 2021

Objective To determine whether pain is associated with gait instability in patients with lumbar disc herniation (LDH). Methods This retrospective cross-sectional study used data from electronic medical records. Among patients with lumbar back pain caused by LDH between January 2017 and July 2019, patients that underwent gait analysis were included. LDH was diagnosed using magnetic resonance imaging. An OptoGait photoelectric cell system was used for gait evaluation. Instability was measured using a gait symmetry index. Multivariate linear regression analysis was performed to determine the association between lumbar pain and gait instability. Results A total of 29 patients (12 females [41.4%] and 17 males [58.6%]; mean ± SD age, 40.6 ± 12.0 years) with LDH were enrolled in the study. With each 1-point increase in lumbar pain on the numeric rating scale, the symmetry index of the stance phase (0.33; 95% confidence interval [CI] 0.04, 0.62), swing phase (0.78; 95% CI 0.14, 1.43) and single support (0.79; 95% CI 0.15, 1.43) increased. Conclusions Gait instability in patients with LDH may occur due to an increase in pain.
Exploring the efficacy and safety of polyene phosphatidylcholine for treatment of drug-induced liver injury using the Roussel Uclaf causality assessment method: a propensity score matching comparison
Authors: Lei Xiaohong , Zhang Jianzhong , Xu Qingling , Li Jing , Qian Yunsong , Zhang Jing , Liu Liangming , Zhong Wei , Wang Yongfeng , Han Xian , Tang Jieting , Zeng Minde , Mao Yimin 
Published: August 2021

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI). Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores <6 were further evaluated by a panel of hepatologists. The primary outcome was the proportion of patients with ALT normalization at discharge. Propensity score matching was used to identify 183 matched pairs of patients (366 patients in total) from 25,927 patients with DILI. Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups. Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.
Advance Care Planning Needs in Idiopathic Pulmonary Fibrosis: A Qualitative Study
Authors: Kalluri Meena , Orenstein Sara , Archibald Nathan , Pooler Charlotte 
Published: August 2021

Introduction: Advance care planning is recommended in chronic respiratory diseases, including Idiopathic Pulmonary Fibrosis. In practice, uptake remains low due to patient, physician and system-related factors, including lack of time, training and guidance on timing, components and content of conversations. Our aim was to explore perspectives, experiences and needs to inform a framework. Methods: We conducted a qualitative study in western Canada, using semi-structured interviews and inductive analysis. Patient, caregiver and health care professional participants described advance care planning experiences with Idiopathic Pulmonary Fibrosis. Results: Twenty participants were interviewed individually: 5 patients, 5 caregivers, 5 home care and 5 acute care health care professionals. Two categories, perceptions and recommendations, were identified with themes and subthemes. Participant perceptions were insufficient information and conversations occur late. Recommendations were: have earlier conversations; have open conversations; provide detailed information; and plan for end-of-life. Patients and caregivers wanted honesty, openness and clarity. Professionals related delayed timing to poor end-of-life care and distressing deaths. Home care professionals described comfort with and an engaged approach to advance care planning. Acute care professionals perceived lack of clarity of roles and described personal, patient and caregiver distress. Interpretation: Analysis of diverse experiences provided further understanding of advance care planning in Idiopathic Pulmonary Fibrosis. Advance care planning is desired by patients and caregivers early in their illness experience. Health care professionals described a need to clarify role, scope and responsibility. Practical guidance and training must be available to care providers to improve competency and confidence in these conversations.
MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumatoid arthritis in an association with the REST/mTOR axis
Authors: Sun Wei , Zhang Yijun , Wang Guanghui 
Published: August 2021

Background It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression. Methods Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for in vivo experiments. Results miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our in vivo study. Conclusion This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.
Do somatosensory deficits predict efficacy of neurorehabilitation using neuromuscular electrical stimulation for moderate to severe motor paralysis of the upper limb in chronic stroke?
Authors: Tsuzuki Keita , Kawakami Michiyuki , Nakamura Takuya , Oshima Osamu , Hijikata Nanako , Suda Mabu , Yamada Yuka , Okuyama Kohei , Tsuji Tetsuya 
Published: August 2021

Background: Various neurorehabilitation programs have been developed to promote recovery from motor impairment of upper extremities. However, the response of patients with chronic-phase stroke varies greatly. Prediction of the treatment response is important to provide appropriate and efficient rehabilitation. This study aimed to clarify whether clinical assessments, such as motor impairments and somatosensory deficits, before treatment could predict the treatment response in neurorehabilitation. Methods: The data from patients who underwent neurorehabilitation using closed-loop electromyography (EMG)-controlled neuromuscular electrical stimulation were retrospectively analyzed. A total of 66 patients with chronic-phase stroke with moderate to severe paralysis were included. The changes from baseline in the Fugl-Meyer Assessment–Upper Extremity (FMA-UE) and the Motor Activity Log-14 (MAL-14) of amount of use (AOU) and quality of movement (QOM) were used to assess treatment response, and multivariate logistic regression analysis was performed using the extracted candidate predictors, such as baseline clinical assessments, to identify predictors of FMA-UE and MAL-14 improvement. Results: FMA-UE and MAL-14 scores improved significantly after the intervention (FMA-UE p < 0.01, AOU p < 0.01, QOM p < 0.01). On multivariate logistic regression analysis, tactile sensory ( p = 0.043) and hand function ( p = 0.030) were both identified as significant predictors of FMA-UE improvement, tactile sensory ( p = 0.047) was a significant predictor of AOU improvement, and hand function ( p = 0.026) was a significant predictor of QOM improvement. The regression equations explained 71.2% of the variance in the improvement of FMA-UE, 69.7% of AOU, and 69.7% of QOM. Conclusion: Both motor and tactile sensory impairments predict improvement in motor function, tactile sensory impairment predicts improvement in the amount of paralytic hand use, and motor impairment predicts improvement in the quality of paralytic hand use following neurorehabilitation treatment in patients with moderate to severe paralysis in chronic-phase stroke. These findings may help select the appropriate treatment for patients with more severe paralysis and to maximize the treatment effect.