bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soft tissue facial changes among adult females during alignment stage of orthodontic treatment: a 3D geometric morphometric study
Authors: Hou Si Yu , Zhou Wenwen , Dai Hongwei , Wong Hai Ming , Wen Yi Feng , Zhou Jianping 
Published: February 2021

Abstract
Background
To investigate changes in facial morphology during the first six months of orthodontic treatment among adult females receiving orthodontic treatment.

Methods
43 adult females receiving orthodontic treatment were randomly recruited. 3D facial images were taken at baseline (T0), three months (T1), and six months (T2) after treatment initiation. Spatially dense facial landmarks were digitized to allow for sufficient details in characterization of facial features. 3D geometric morphometrics and multivariate statistics were used to investigate changes in mean and variance of facial shape and facial form associated with treatment.

Results
We observed statistically significant changes in facial shape across the three treatment stages (p = 0.0022). Pairwise comparisons suggested significant changes from T0 to T1 (p = 0.0045) and from T0 to T2 (p = 0.0072). Heatmap visualization indicated that the buccal and temporal region were invaginated while the labial region became protruded with treatment. The magnitude of shape change was 0.009, 0.004, and 0.010 from T0 to T1, T1 to T2, and T0 to T2, respectively, in unit of Procrustes distance. The average magnitude of change per-landmark was 1.32 mm, 0.21 mm, and 1.34 mm, respectively. Changes in mean facial form were not statistically significant (p = 0.1143). No changes in variance of facial shape were observed across treatment stages (p > 0.05).

Conclusion
Rate of facial changes was twice as fast during the first three months as that during fourth to sixth month. Buccal and temporal region became invaginated while labial region became protruded with treatment.
Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a preliminary in vitro study
Authors: Weng Jie , Chen Bi , Xie Mengying , Wan Xinlong , Wang Peng , Zhou Xiaoming , Zhou Zhiliang , Mei Jin , Wang Liang , Huang Duping , Wang Zhibin , Wang Zhiyi , Chen Chan 
Published: February 2021

Abstract
Background
Advances in regenerative medicine technologies have been strongly proposed in the management of thyroid diseases. Mechanistically, the adoption of thyroid bioengineering requires a scaffold that shares a similar three-dimensional (3D) space structure, biomechanical properties, protein component, and cytokines to the native extracellular matrix (ECM).

Methods
24 male New Zealand white rabbits were used in this experimental study. The rabbit thyroid glands were decellularized by immersion/agitation decellularization protocol. The 3D thyroid decellularization scaffolds were tested with histological and immunostaining analyses, scanning electron microscopy, DNA quantification, mechanical properties test, cytokine assay and cytotoxicity assays. Meanwhile, the decellularization scaffold were seeded with human thyroid follicular cells, cell proliferation and thyroid peroxidase were determined to explore the biocompatibility in vitro.

Results
Notably, through the imaging studies, it was distinctly evident that our protocol intervention minimized cellular materials and maintained the 3D spatial structure, biomechanical properties, ECM composition, and biologic cytokine. Consequently, the decellularization scaffold was seeded with human thyroid follicular cells, thus strongly revealing its potential in reinforcing cell adhesion, proliferation, and preserve important protein expression.

Conclusions
The adoption of our protocol to generate a decellularized thyroid scaffold can potentially be utilized in transplantation to manage thyroid diseases through thyroid bioengineering.
ImmunoPET imaging of human CD8+ T cells with novel 68Ga-labeled nanobody companion diagnostic agents
Authors: Zhao Haitao , Wang Chao , Yang Yanling , Sun Yan , Wei Weijun , Wang Cheng , Wan Liangrong , Zhu Cheng , Li Lianghua , Huang Gang , Liu Jianjun 
Published: February 2021

Abstract
Background
Although immunotherapy has revolutionized treatment strategies for some types of cancers, most patients failed to respond or obtain long-term benefit. Tumor-infiltrating CD8+ T lymphocytes are closely related to the treatment outcome and prognosis of patients. Therefore, noninvasive elucidation of both systemic and tumor-infiltrating CD8+ T lymphocytes is of extraordinary significance for patients during cancer immunotherapy. Herein, a panel of 68Ga-labeled Nanobodies were designed and investigated to track human CD8+ T cells in vivo through immuno-positron emission tomography (immunoPET).

Results
Among the screened Nanobodies, SNA006a showed the highest binding affinity and specificity to both human CD8 protein and CD8+ cells in vitro, with the equilibrium dissociation constant (KD) of 6.4 × 10−10 M and 4.6 × 10−10 M, respectively. 68Ga-NOTA-SNA006 was obtained with high radiochemical yield and purity, and stayed stable for at least 1 h both in vitro and in vivo. Biodistribution and Micro-PET/CT imaging studies revealed that all tracers specifically concentrated in the CD8+ tumors with low accumulation in CD8− tumors and normal organs except the kidneys, where the tracer was excreted and reabsorbed. Notably, the high uptake of 68Ga-NOTA-SNA006a in CD8+ tumors was rapid and persistent, which reached 24.41 ± 1.00% ID/g at 1.5 h after intravenous injection, resulting in excellent target-to-background ratios (TBRs). More specifically, the tumor-to-muscle, tumor-to-liver, and CD8+ to CD8− tumor was 28.10 ± 3.68, 5.26 ± 0.86, and 19.58 ± 2.70 at 1.5 h, respectively. Furthermore, in the humanized PBMC-NSG and HSC-NPG mouse models, 68Ga-NOTA-SNA006a accumulated in both CD8+ tumors and specific tissues such as liver, spleen and lung where human CD8 antigen was overexpressed or CD8+ T cells located during immunoPET imaging.

Conclusions
68Ga-NOTA-SNA006a, a novel Nanobody tracer targeting human CD8 antigen, was developed with high radiochemical purity and high affinity. Compared with other candidates, the long retention time, low background, excellent TBRs of 68Ga-NOTA-SNA006a make it precisely track the human CD8+ T cells in mice models, showing great potential for immunotherapy monitoring and efficacy evaluation.
Physician–patient communication in decision-making about Caesarean sections in eight district hospitals in Bangladesh: a mixed-method study
Authors: Doraiswamy Sathyanarayanan , Billah Sk Masum , Karim Farhana , Siraj Md Shahjahan , Buckingham Alan , Kingdon Carol 
Published: February 2021

Abstract
Background
Caesarean sections (CS) in Bangladesh have risen eight-fold in the last 15 years. Few studies have explored why. Anecdotally, physicians suggest maternal request for CS is a reason. Women and families suggest physicians influence their decision-making. The aim of this research was to understand more about the decision-making process surrounding CS by exploring physician–patient communication leading to informed-consent for the operation.

Methods
We conducted a mixed-method study using structured observations with the Option Grid Collaborative’s OPTION5 tool and interviews with physicians and women between July and December 2018. Study participants were recruited from eight district public-sector hospitals. Eligibility criteria for facilities was ≥ 80 births every month; and for physicians, was that they had performed CSs. Women aged ≥ 18 years, providing consent, and delivering at a facility were included in the observation component; primigravid women delivering by CS were selected for the in-depth interviews. Quantitative data from observations were analysed using descriptive statistics. Following transcription and translation, a preliminary coding framework was devised for the qualitative data analysis. We combined both inductive and deductive approaches in our thematic analysis.

Results
In total, 306 labour situations were observed, and interviews were conducted with 16 physicians and 32 women who delivered by CS (16 emergency CS; 16 elective CS). In 92.5% of observations of physician–patient communication in the context of labour situations, the OPTION5 mean scores were low (5–25 out of 100) for presenting options, patient partnership, describing pros/cons, eliciting patient preferences and integrating patient preferences. Interviews found that non-clinical factors prime both physicians and patients in favour of CS prior to the clinical encounter in which the decision to perform a CS is documented. These interactions were both minimal in content and limited in purpose, with consent being an artefact of a process involving little communication.

Conclusions
Insufficient communication between physicians and patients is one of many factors driving increasing rates of caesarean section in Bangladesh. While this single clinical encounter provides an opportunity for practice improvement, interventions are unlikley to impact rates of CS without simultaneoulsy addressing physician, patient and health system contextual factors too.
Comparing burnout and work-life balance among specialists in internal medicine: the role of inpatient vs. outpatient workplace
Authors: Hussenoeder Felix S. , Bodendieck Erik , Jung Franziska , Conrad Ines , Riedel-Heller Steffi G. 
Published: February 2021

AbstractBackgroundCompared to the general population, physicians are more likely to experience increased burnout and lowered work-life balance. In our article, we want to analyze whether the workplace of a physician is associated with these outcomes.MethodsIn September 2019, physicians from various specialties answered a comprehensive questionnaire. We analyzed a subsample of 183 internists that were working full time, 51.4% were female.ResultsMultivariate analysis showed that internists working in an outpatient setting exhibit significantly higher WLB and more favorable scores on all three burnout dimensions. In the regression analysis, hospital-based physicians exhibited higher exhaustion, cynicism and total burnout score as well as lower WLB.ConclusionsPhysician working at hospitals exhibit less favorable outcomes compared to their colleagues in outpatient settings. This could be a consequence of workplace-specific factors that could be targeted by interventions to improve physician mental health and subsequent patient care.
Renal dysfunction improves risk stratification and may call for a change in the management of intermediate- and high-risk acute pulmonary embolism: results from a multicenter cohort study with external validation
Authors: Chopard Romain , Jimenez David , Serzian Guillaume , Ecarnot Fiona , Falvo Nicolas , Kalbacher Elsa , Bonnet Benjamin , Capellier Gilles , Schiele François , Bertoletti Laurent , Monreal Manuel , Meneveau Nicolas 
Published: February 2021

Abstract
Background
Renal dysfunction influences outcomes after pulmonary embolism (PE). We aimed to determine the incremental value of adding renal dysfunction, defined by estimated glomerular filtration rate (eGFR), on top of the European Society of Cardiology (ESC) prognostic model, for the prediction of 30-day mortality in acute PE patients, which in turn could lead to the optimization of acute PE management.

Methods
We performed a multicenter, non-interventional retrospective post hoc analysis based on a prospectively collected cohort including consecutive confirmed acute PE stratified per ESC guidelines. We first identified which of three eGFR formulae most accurately predicted death. Changes in global model fit, discrimination, calibration and reclassification parameters were evaluated with the addition of eGFR to the prognostic model.

Results
Among 1943 patients (mean age 67.3 (17.1), 50.4% women), 107 (5.5%) had died at 30 days. The 4-variable Modification of Diet in Renal Disease (eGFRMDRD4) formula predicted death most accurately. In total, 477 patients (24.5%) had eGFRMDRD4 < 60 ml/min. Observed mortality was higher for intermediate–low-risk and high-risk PE in patients with versus without renal dysfunction. The addition of eGFRMDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC model. Reclassification parameters were significantly increased, yielding 18% reclassification of predicted mortality (p < 0.001). Predicted mortality reclassifications across risk categories were as follows: 63.1% from intermediate–low risk to eGFR-defined intermediate–high risk, 15.8% from intermediate–high risk to eGFR-defined intermediate–low risk, and 21.0% from intermediate–high risk to eGFR-defined high risk. External validation in a cohort of 14,234 eligible patients from the RIETE registry confirmed our findings with a significant improvement of Harrell’s C index and reclassification parameters.

Conclusion
The addition of eGFRMDRD4-derived renal dysfunction on top of the prognostic algorithm led to risk reclassification within the intermediate- and high-risk PE categories. The impact of risk stratification integrating renal dysfunction on therapeutic management for acute PE requires further studies.
5′-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis
Authors: Wu Yingmin , Yang Xiangling , Jiang Guanmin , Zhang Haisheng , Ge Lichen , Chen Feng , Li Jiexin , Liu Huanliang , Wang Hongsheng 
Published: February 2021

Abstract
Background
tRNA-derived small RNAs (tDRs), which are widely distributed in human tissues including blood and urine, play an important role in the progression of cancer. However, the expression of tDRs in colorectal cancer (CRC) plasma and their potential diagnostic values have not been systematically explored.

Methods
The expression profiles of tDRs in plasma of CRC and health controls (HCs) are investigated by small RNA sequencing. The level and diagnostic value of 5′-tRF-GlyGCC are evaluated by quantitative PCR in plasma samples from 105 CRC patients and 90 HCs. The mechanisms responsible for biogenesis of 5′-tRF-GlyGCC are checked by in vitro and in vivo models.

Results
5′-tRF-GlyGCC is dramatically increased in plasma of CRC patients compared to that of HCs. The area under curve (AUC) for 5′-tRF-GlyGCC in CRC group is 0.882. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with 5′-tRF-GlyGCC improves the AUC to 0.926. Consistently, the expression levels of 5′-tRF-GlyGCC in CRC cells and xenograft tissues are significantly greater than that in their corresponding controls. Blood cells co-cultured with CRC cells or mice xenografted with CRC tumors show increased levels of 5′-tRF-GlyGCC. In addition, we find that the increased expression of 5′-tRF-GlyGCC is dependent on the upregulation of AlkB homolog 3 (ALKBH3), a tRNA demethylase which can promote tRNA cleaving to generate tDRs.

Conclusions
The level of 5′-tRF-GlyGCC in plasma is a promising diagnostic biomarker for CRC diagnosis.
RIP-seq reveals LINE-1 ORF1p association with p-body enriched mRNAs
Authors: Briggs Erica M. , McKerrow Wilson , Mita Paolo , Boeke Jef D. , Logan Susan K. , Fenyö David 
Published: February 2021

Abstract
Background
Long INterspersed Element-1 (LINE-1) is an autonomous retroelement able to “copy-and-paste” itself into new loci of the host genome through a process called retrotransposition. The LINE-1 bicistronic mRNA codes for two proteins, ORF1p, a nucleic acid chaperone, and ORF2p, a protein with endonuclease and reverse transcriptase activity. Both proteins bind LINE-1 mRNA in cis and are necessary for retrotransposition. While LINE-1 transcription is usually repressed in most healthy somatic cells through a plethora of mechanisms, ORF1p expression has been observed in nearly 50% of tumors, and new LINE-1 insertions have been documented in a similar fraction of tumors, including prostate cancer.

Results
Here, we utilized RNA ImmunoPrecipitation (RIP) and the L1EM analysis software to identify ORF1p bound RNA in prostate cancer cells. We identified LINE-1 loci that were expressed in parental androgen sensitive and androgen independent clonal derivatives. In all androgen independent cells, we found higher levels of LINE-1 RNA, as well as unique expression patterns of LINE-1 loci. Interestingly, we observed that ORF1p bound many non-LINE-1 mRNA in all prostate cancer cell lines evaluated, and polyA RNA, and RNA localized in p-bodies were especially enriched. Furthermore, the expression levels of RNAs identified in our ORF1p RIP correlated with RNAs expressed in LINE-1 positive tumors from The Cancer Genome Atlas (TCGA).

Conclusion
Our results show a significant remodeling of LINE-1 loci expression in androgen independent cell lines when compared to parental androgen dependent cells. Additionally, we found that ORF1p bound a significant amount of non-LINE-1 mRNA, and that the enriched ORF1p bound mRNAs are also amplified in LINE-1 expressing TCGA prostate tumors, indicating the biological relevance of our findings to prostate cancer.
Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer’s disease: a Mendelian randomization study
Authors: Ou Ya-Nan , Yang Yu-Xiang , Shen Xue-Ning , Ma Ya-Hui , Chen Shi-Dong , Dong Qiang , Tan Lan , Yu Jin-Tai 
Published: February 2021

Abstract
Background
Observational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach.

Methods
Genetic proxies from genome-wide association studies of BP traits and BP-lowering variants in genes encoding AHM targets were extracted. Estimates were calculated by inverse-variance weighted method as the main model. MR Egger regression and leave-one-out analysis were performed to identify potential violations.

Results
There was limited evidence that genetically predicted SBP/diastolic BP level affected AD risk based on 400/398 single nucleotide polymorphisms (SNPs), respectively (all P > 0.05). Suitable genetic variants for β-blockers (1 SNP), angiotensin receptor blockers (1 SNP), calcium channel blockers (CCBs, 45 SNPs), and thiazide diuretics (5 SNPs) were identified. Genetic proxies for CCB [odds ratio (OR) = 0.959, 95% confidence interval (CI) = 0.941–0.977, P = 3.92 × 10−6] and overall use of AHMs (OR = 0.961, 95% CI = 0.944–0.978, P = 5.74 × 10−6, SNPs = 52) were associated with a lower risk of AD. No notable heterogeneity and directional pleiotropy were identified (all P > 0.05). Additional analyses partly support these results. No single SNP was driving the observed effects.

Conclusions
This MR analysis found evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention.
Outcomes of severe systemic rheumatic disease patients requiring extracorporeal membrane oxygenation
Authors: Bay Pierre , Lebreton Guillaume , Mathian Alexis , Demondion Pierre , Desnos Cyrielle , Chommeloux Juliette , Hékimian Guillaume , Bréchot Nicolas , Nieszkowska Ania , Schmidt Matthieu , Cohen-Aubart Fleur , Leprince Pascal , Luyt Charles-Edouard , Amoura Zahir , Combes Alain , Pineton de Chambrun Marc 
Published: February 2021

Abstract
Background
Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can require intensive care unit (ICU) admission because of multiorgan involvement with end-organ failure(s). Critically ill SRD patients requiring extracorporeal membrane oxygenation (ECMO) were studied to gain insight into their characteristics and outcomes.

Methods
This French monocenter, retrospective study included all SRD patients requiring venovenous (VV)- or venoarterial (VA)-ECMO admitted to a 26-bed ECMO-dedicated ICU from January 2006 to February 2020. The primary endpoint was in-hospital mortality.

Results
Ninety patients (male/female ratio: 0.5; mean age at admission: 41.6 ± 15.2 years) admitted to the ICU received VA/VV-ECMO, respectively, for an SRD-related flare (n = 69, n = 38/31) or infection (n = 21, n = 10/11). SRD was diagnosed in-ICU for 31 (34.4%) patients. In-ICU and in-hospital mortality rates were 48.9 and 51.1%, respectively. Nine patients were bridged to cardiac (n = 5) or lung transplantation (n = 4), or left ventricular assist device (n = 2). The Cox multivariable model retained the following independent predictors of in-hospital mortality: in-ICU SRD diagnosis, day-0 Simplified Acute Physiology Score (SAPS) II score ≥ 70 and arterial lactate ≥ 7.5 mmol/L for VA-ECMO–treated patients; diagnosis other than vasculitis, day-0 SAPS II score ≥ 70, ventilator-associated pneumonia and arterial lactate ≥ 7.5 mmol/L for VV-ECMO–treated patients.

Conclusions
ECMO support is a relevant rescue technique for critically ill SRD patients, with 49% survival at hospital discharge. Vasculitis was independently associated with favorable outcomes of VV-ECMO–treated patients. Further studies are needed to specify the role of ECMO for SRD patients.
High-fidelity elastic Green’s functions for subduction zone models consistent with the global standard geodetic reference system
Authors: Hori Takane , Agata Ryoichiro , Ichimura Tsuyoshi , Fujita Kohei , Yamaguchi Takuma , Iinuma Takeshi 
Published: February 2021

AbstractGreen’s functions (GFs) for elastic deformation due to unit slip on the fault plane comprise an essential tool for estimating earthquake rupture and underground preparation processes. These estimation results are often applied to generate important information for public such as seismic and tsunami hazard assessments. So, it is important to minimize the distortion of the estimation results on the numerical models used for calculating GFs to guarantee assessment reliability. For this purpose, we here calculated GFs based on a numerical model that is of high fidelity to obtain realistic topography and subsurface structural models of the Earth. We targeted two well-known subduction zones in Japan, the Nankai Trough and the Japan Trench. For these subduction zones, databases for realistic topography and subsurface structural models of the Earth are available in the “Japan integrated velocity structure model version 1”, which was proposed for earthquake hazard assessments conducted by the Japanese government. Furthermore, we eliminated the inconsistency in processing calculated GFs and space geodetic observation data for surface displacements, which is often overlooked, by using the same coordinate system. The ellipsoidal shape of the Earth, which is often approximated with a projected plane or a spherical shape, was also incorporated by faithfully following the definitions of the coordinate systems in Geodetic Reference System 1980, which is the global standard for space geodesy. To calculate elastic GFs based on such high-fidelity subduction zone databases with the ellipsoidal shape of the Earth, we introduced the finite element (FE) method. In the FE meshes, the resolution of the topography and subsurface structure is the same as that of the original databases. Recent development of the state-of-the-art computation techniques for the rapid calculation of crustal deformation using large-scale FE models allows for GF calculation based on such a high-fidelity model. However, it is generally not easy to perform such calculations. Thus, we released a library for the GFs calculated with 1-km grid spacing on the ground surface in this study to the geoscience community on a web server, aiming to contribute more reliable seismic and tsunami hazard assessment.