bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups
Authors: Murphy Susan L , Chen Yen T , Lee Yvonne C , Carns Mary , Aren Kathleen , Korman Benjamin , Hinchcliff Monique , Varga John 
Published: August 2022

Abstract

Objectives
Symptoms of people who have SSc are heterogeneous and difficult to address clinically. Because diverse symptoms often co-occur and may share common underlying mechanisms, identifying symptoms that cluster together may better target treatment approaches. We sought to identify and characterize patient subgroups based on symptom experience.

Methods
An exploratory hierarchical agglomerative cluster analysis was conducted to identify subgroups from a large SSc cohort from a single US academic medical centre. Patient-reported symptoms of pain interference, fatigue, sleep disturbance, dyspnoea, depression and anxiety were used for clustering. A multivariate analysis of variance (MANOVA) was used to examine the relative contribution of each variable across subgroups. Analyses of variance were performed to determine participant characteristics based on subgroup assignment. Presence of symptom clusters were tallied within subgroup.

Results
Participants (n = 587; 84% female, 41% diffuse cutaneous subtype, 59% early disease) divided into three subgroups via cluster analysis based on symptom severity: (i) no/minimal, (ii) mild, and (iii) moderate. Participants in mild and moderate symptoms subgroups had similar disease severity, but different symptom presentation. In the mild symptoms subgroup, pain, fatigue and sleep disturbance was the main symptom cluster. Participants in the moderate symptoms subgroup were characterized by co-occurring pain, fatigue, sleep disturbance, depression and anxiety.

Conclusion
Identification of distinct symptom clusters, particularly among SSc patients who experience mild and moderate symptoms, suggests potential differences in treatment approach and in mechanisms underlying symptom experience that require further study.
Clinically suspect arthralgia patients with a low educational attainment have an increased risk of developing inflammatory arthritis
Authors: Khidir Sarah J H , Boeren Anna M P , Boonen Annelies , de Jong Pascal H P , van Mulligen Elise , van der Helm-van Mil Annette H M 
Published: August 2022

Abstract

Objectives
Cross-sectional studies have shown that rheumatoid arthritis is more prevalent among people with a lower educational attainment. No longitudinal data are present on educational attainment in the at-risk phase of clinically suspect arthralgia (CSA). We therefore analysed the association between educational attainment and progression from CSA to inflammatory arthritis (IA), and performed mediation analysis with subclinical joint inflammation to elucidate pathways of this association.

Methods
A total of 521 consecutive patients presenting with CSA were followed for IA development during median 25 months. Educational attainment was defined as low (lower secondary vocational education), intermediate or high (college/university education). Subclinical inflammation in hand and foot joints was measured at presentation with contrast enhanced 1.5 T-MRI. Cox-regression was used to analyse IA development per educational attainment. A three-step mediation analysis evaluated whether subclinical joint inflammation was intermediary in the path between educational attainment and IA development, before and after age correction. Association between educational attainment and IA development was verified in an independent CSA cohort.

Results
Low educational attainment was associated with increased IA development (HR = 2.35, 95% CI = 1.27, 4.33, P = 0.006), independent of BMI and current smoking status (yes/no). Moreover, patients with a low educational attainment had higher levels of subclinical inflammation, which also was associated with IA development. Partial mediation effect of subclinical inflammation was observed in the relationship between education and IA development. Low educational attainment was also associated with increased IA development in the validation cohort (HR = 5.72, 95% CI = 1.36, 24.08, P = 0.017).

Conclusion
This is the first study providing evidence that lower educational attainment is associated with a higher risk of progressing from arthralgia to IA. This effect was partially mediated by subclinical joint inflammation.
IPO7 Promotes Odontoblastic Differentiation and Inhibits Osteoblastic Differentiation Through Regulation of RUNX2 Expression and Translocation
Authors: Zhang Yue , Zhang Hao , Xiao Ziqiu , Yuan Guohua , Yang Guobin 
Published: August 2022

Abstract
RUNX2, an important transcriptional factor for both odontoblastic and osteoblastic differentiation, is upregulated during osteoblastic differentiation, but downregulated during late odontoblastic differentiation. However, the specific mechanism of the different RUNX2 expression in bone and dentin remains largely unknown. Importin 7 (IPO7), a member of the karyopherin β-superfamily, mediates nucleocytoplasmic transport of proteins. In this study, we found that IPO7 was increasingly expressed from pre-odontoblasts to mature odontoblasts. IPO7 expression was increased with odontoblastic differentiation of mouse dental papilla cells (mDPCs) and knockdown of IPO7-inhibited cell differentiation. While in MC3T3-E1 cells, IPO7 was decreased during osteoblastic differentiation and knockdown of IPO7-promoted cell differentiation. In mPDCs, IPO7 was able to bind with some odontoblastic transcription factors, and imported them into the nucleus, but not with RUNX2. Furthermore, IPO7 inhibited the total RUNX2 expression by promoting HDAC6 nuclear localization during odontoblastic differentiation. However, in MC3T3-E1 cells, IPO7 inhibited the nuclear distribution of RUNX2 but did not affect the total protein level of RUNX2. In conclusion, we found that IPO7 promotes odontoblastic differentiation and inhibits osteoblastic differentiation through regulating RUNX2 expression and translocation differently.
Evaluation of the Impact of Glycemic Control on Mean Platelet Volume and Platelet Activation in Children with Type 1 Diabetes
Authors: Söbü Elif , Demir Yenigürbüz Fatma , Özçora Gül Demet Kaya , Köle Mehmet Tolga 
Published: August 2022

Abstract

Objective
The studies evaluating cases with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the adult population reported hyperreactive platelets and increased activation of prothrombotic factors, resulting in an increased risk of thrombosis. The aim of this study was to evaluate the effects of poor glycemic control and the duration of diabetes on platelet parameters in pediatric population.

Methods
The study included 366 children, out of which 144 (39.3%) were included in the T1DM group and 222 (60.6%) in the healthy control group. The platelet count, mean platelet volume (MPV), platelet distribution width and plateletcrit values were recorded. The children with T1DM were divided into three groups as per their glycated hemoglobin (HbA1c) levels, good (&lt;7.5%), moderate (7.5–9%) and poor metabolic control (&gt;9%).

Results
No significant difference in the MPV level between the T1DM (7.41 ± 1.49 fl) and control (7.15 ± 1.23 fl) groups was observed. However, the MPV levels were significantly higher in the poor glycemic control group than in the healthy control group (p = 0.026). Furthermore, as the duration of diabetes and HbA1c levels increased, the MPV levels also increased (p &lt; 0.001, p = 0.441).

Conclusion
This study suggested as the duration of diabetes and HbA1c levels increased, the MPV levels also increases. Evaluation of hematological parameters can be a cheap and useful method in the evaluation of diabetes regulation in patients with diabetes.
Diagnostic Yield of Cone-beam–Derived Augmented Fluoroscopy and Ultrathin Bronchoscopy Versus Conventional Navigational Bronchoscopy Techniques
Authors: DiBardino David M. , Kim Roger Y. , Cao Yulei , Andronov Michelle , Lanfranco Anthony R. , Haas Andrew R. , Vachani Anil , Ma Kevin C. , Hutchinson Christoph T. 
Published: August 2022

Background:
Pulmonary nodules suspicious for lung cancer are frequently diagnosed. Evaluating and optimizing the diagnostic yield of lung nodule biopsy is critical as innovation in bronchoscopy continues to progress.

Methods:
This is a retrospective cohort study. Consecutive patients undergoing guided bronchoscopy for suspicious pulmonary nodule(s) between February 2020 and July 2021 were included. The cone-beam computed tomography (CBCT)+ radial endobronchial ultrasound (r-EBUS) group had their procedure using CBCT-derived augmented fluoroscopy along with r-EBUS. The CBCT+ ultrathin bronchoscope (UTB)+r-EBUS group had the same procedure but with the use of an ultrathin bronchoscope. The r-EBUS group underwent r-EBUS guidance without CBCT or augmented fluoroscopy. We used multivariable logistic regression to compare diagnostic yield, adjusting for confounding variables.

Results:
A total of 116 patients were included. The median pulmonary lesion diameter was 19.5 mm (interquartile range, 15.0 to 27.5 mm), and 91 (78.4%) were in the peripheral half of the lung. Thirty patients (25.9%) underwent CBCT+UTB, 27 (23.3%) CBCT, and 59 (50.9%) r-EBUS alone with unadjusted diagnostic yields of 86.7%, 70.4%, and 42.4%, respectively (P<0.001). The adjusted diagnostic yields were 85.0% (95% CI, 68.6% to 100%), 68.3% (95% CI, 50.1% to 86.6%), and 44.5% (95% CI, 31.0% to 58.0%), respectively. There was significantly more virtual navigational bronchoscopy use in the r-EBUS group (45.8%) compared with the CBCT+UTB (13.3%) and CBCT (18.5%) groups, respectively. CBCT procedures required dose area product radiation doses of 7602.5 µGym2.

Conclusion:
Compared with the r-EBUS group, CBCT + UTB + r-EBUS was associated with higher navigational success, fewer nondiagnostic biopsy results, and a higher diagnostic yield. CBCT procedures are associated with a considerable radiation dose.
Nano assembly of plasmonic probe-virus particles enabled rapid and ultrasensitive point-of-care SARS-CoV-2 detection
Authors: Park Younggeun , Ryu Byunghoon , Ki Seungjune , Chen Mingze , Liang Xiaogan , Kurabayashi Katsuo 
Published: August 2022

AbstractThe current COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has become a major public health concern. The ability to identify the virus’s presence in infected hosts with sufficient speed and sensitivity is critical to control the epidemic timely. Here, we use self-assembly of arrayed gold nanoparticles (AuNPs) on the coronavirus, which we call the “plasmo-virus particle,” to achieve a rapid, sensitive, sample preparation-free assay enabling direct detection of SARS-CoV-2 in a point-of-care (POC) setting. The AuNPs of the plasmo-virus particle serve as plasmonic nanoprobes that specifically bind to the spike protein (S-protein) sites on the surface of SARS-CoV-2. Optical interactions between the self-assembled plasmonic nanoprobes generate multiple modes of highly enhanced plasmonic coupling. Measuring changes of the multimode plasmonic coupling-induced extinction peaks allows for quantifying SARS-CoV-2 at low titers with a limit of detection (LOD) of 1.4 × 101 pfu/mL. Using a miniaturized standalone biochip reading device, we further demonstrate the nano assembly assay for smartphone-operated SARS-CoV-2 detection for viral transport medium (VTM) samples within 10 min without any sample purification steps. We anticipate that the high sensitivity and speed of the POC detection performance of this biosensor technology could be broadly accepted for timely personalized diagnostics of infectious agents under low-resource settings.
Brief report: Determinants of potential sexual activity reduction in the face of the Monkeypox epidemic
Authors: Wang Haoyi , d’Abreu de Paulo Kennedy J.I. , Gültzow Thomas , Zimmermann Hanne M.L. , Jonas Kai. J. 
Published: August 2022

AbstractThe current monkeypox epidemic is most prevalent among men-who-have-sex-with-men (MSM). Vaccination programs are being rolled-out to curb the epidemic. Behavioural measures have been called for as well, e.g., by the WHO to reduce the number of sexual partners and sexual activity. We investigated intentions and determinants among Dutch MSM to follow such measures. Early July 2022, 394 MSM answered an online questionnaire. The overall intentions to reduce number of partners and sexual activity was high, but only a minority had developed definite intentions. Determinant analysis revealed that dating/open relationship status was a positive predictor, vaccination intentions did not predict sexual behaviour change; those not on PrEP were more likely to change their sexual behaviour. Monkeypox infection concern was negatively related to weaker intentions and only predicted definite intentions. Our results show that additional public health measures are necessary to reach and convince MSM to engage in sexual behaviour change.
Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference
Authors: Gabriel Daniel B.K. , Liley Anna E. , Franks Hunter , Tutaj Monika , Dwinell Melinda R. , de Jong Tristan , Williams Robert W. , Mulligan Megan K. , Chen Hao , Simon Nicholas W. 
Published: August 2022

AbstractSubstance use disorder (SUD) is associated with a cluster of cognitive disturbances that engender vulnerability to ongoing drug seeking and relapse. Two of these endophenotypes—risky decision-making and impulsivity—are amplified in individuals with substance use disorder and are augmented by repeated exposure to illicit drugs. Identifying genetic factors underlying variability in these traits is critical for early identification, prevention, and treatment of SUD-vulnerable individuals. Here, we compared risky decision-making and different facets of impulsivity between two fully inbred substrains of Lewis rats—LEW/NCrl and LEW/NHsd. We performed whole genome sequencing of both substrain to identify almost all relevant variants. We observed substantial differences in risky decision-making and impulsive behaviors. Relative to LEW/HHsd, the LEW/NCrl substrain accepts higher risk options in a decision-making task and higher rates of premature responses in thedifferential reinforcement of low rates of responding(DRL) task. These phenotypic differences were more pronounced in females than males. We defined a total of ∼9,000 polymorphisms between these substrains at 40X whole genome short-read coverage. Roughly half of variants are located within a single 1.5 Mb region of chromosome 8, but none impact protein-coding regions. In contrast, other variants are widely distributed, and of these 38 are predicted to cause protein-coding variants. In conclusion, Lewis rat substrains differ significantly in risk-taking and impulsivity and only a small number of easily mapped variants are likely to be causal. Sequencing combined with a reduced complexity cross (RCC) should enable identification of one or more variants underlying multiple complex addiction-relevant traits.
Next generation digital PCR: high dynamic range single molecule DNA counting via ultra-partitioning
Authors: Shum Eleen Y. , Lai Janice H. , Li Sixing , Lee Haeun G. , Soliman Jesse , Raol Vedant K. , Lee Cavina K. , Fodor Stephen P.A. , Fan H. Christina 
Published: August 2022

ABSTRACTDigital PCR (dPCR) was first conceived for single molecule quantitation. However, current dPCR systems often require DNA templates to share partitions due to limited partitioning capacities. Here, we introduce Ultra-dPCR, a next generation dPCR system where DNA counting is performed in a single-molecule regimen through a 6-log dynamic range using a swift and parallelized workflow. Each Ultra-dPCR reaction is divided into >30 million partitions without microfluidics to achieve single template occupancy. Combined with a unique emulsion chemistry, partitions are optically clear and enable the use of a 3D imaging technique to rapidly detect DNA-positive partitions. Single molecule occupancy also allows for more straightforward multiplex assay development due to the absence of partition-specific competition. As a proof-of-concept, we developed a 222-plex Ultra-dPCR assay and demonstrated its potential use as a rapid, low-cost screening assay for non-invasive prenatal testing (NIPT) for as low as 4% trisomy fraction samples with high precision, accuracy, and reproducibility.
Quantitative multiplexed imaging of chromatin ultrastructure with Decode-PAINT
Authors: Sasaki Hiroshi M. , Kishi Jocelyn Y. , Wu Chao-ting , Beliveau Brian J. , Yin Peng 
Published: August 2022

AbstractSuper-resolution chromatin imaging techniques are emerging as powerful tools for spatial genomics. However, it remains challenging to visualize the genome on the order of tens of nanometers, a scale that can reveal rich structural detail about the nuclear organization. Here we introduce Decode-PAINT, a multiplexed in situ method, which leverages rapid diffraction-limited pre-decoding and DNA-PAINT (DNA points accumulation for imaging nanoscale topography). Decode-PAINT visualizes multiple discrete genomic regions at a resolution close to the nucleosome scale with a simple and easy-to-implement optical setup, reduces total imaging time by omitting multiple rounds of single-molecule recording, and enables the interrogation of the ultrastructure of the targets with <12 nm lateral and <20 nm axial resolution. We showcase the ability of our approach to perform multiplexed, high-resolution profiling of chromatin structure by performing targeted imaging of nine regions of active and inactive X chromosomes in individual cells. In short, Decode-PAINT accelerates in situ structural genomics.
A spatiotemporal gradient of mesoderm assembly governs cell fate and morphogenesis of the early mammalian heart
Authors: Dominguez Martin H. , Krup Alexis Leigh , Muncie Jonathon M. , Bruneau Benoit G. 
Published: August 2022

AbstractUsing four-dimensional whole-embryo light sheet imaging with improved and accessible computational tools, we longitudinally reconstruct early murine cardiac development at single-cell resolution. Nascent mesoderm progenitors form opposing density and motility gradients, converting the temporal birth sequence of gastrulation into a spatial anterolateral-to-posteromedial arrangement. Migrating precardiac mesoderm doesn’t strictly preserve cellular neighbor relationships; spatial patterns only become solidified as the cardiac crescent emerges. Progenitors undergo a heretofore unknown mesenchymal-to-epithelial transition, with a first heart field (FHF) ridge apposing a motile juxtacardiac field (JCF). Anchored along the ridge, the FHF epithelium rotates the JCF forward due to push-pull morphodynamics of the second heart field, which forms the nascent heart tube. In Mesp1 mutants that fail to make a cardiac crescent, mesoderm remains highly motile but directionally incoherent, resulting in density gradient inversion. Our practicable live embryo imaging approach defines spatial origins and behaviors of cardiac progenitors, and identifies their unanticipated morphological transitions.
Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord
Authors: Ripoll Chantal , Poulen Gaetan , Chevreau Robert , Lonjon Nicolas , Vachiery-Lahaye Florence , Bauchet Luc , Hugnot Jean-Philippe 
Published: August 2022

AbstractSpinal cord ependymal cells have stem cell properties in mice. They surround the central canal and keep expressing spinal cord developmental transcription factors. Similar cells exist in young humans however their persistence with aging is debated.We clarified this issue by collecting 17 spinal cords from organ donors, aged between 37 and 83 years old. We examined the presence of ependymal cells using immunohistochemistry on lightly-fixed tissue.We found the presence of cells expressing the typical ependymal marker FOXJ1 in the spinal cord central region in 100% of cases. In addition, a lumen surrounded by FOXJ1+ cells was observed in half of the cases. Like in mice, these human ependymal cells maintain the expression of SOX2 and PAX6 proteins together with RFX2 a master transcriptional regulator of ciliogenesis and ARL13B, a regulatory GTPase enriched in cilia. Reminiscent of the situation observed in mice and in young human spinal cord, a fetal-like regionalization of neurodevelopmental transcription factors was observed in three donors aged over 75 years: MSX1 and ARX/FOXA2 was preferentially expressed by dorsal and ventral ependymal cells, respectively.These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life. The persistence of these cells in humans opens new opportunities to regenerate the spinal cord.
Ligand Binding Free Energy Evaluation by Monte Carlo Recursion
Authors: de Souza Joao Victor , Nogueira Victor H. R. , Nascimento Alessandro S. 
Published: August 2022

AbstractThe correct evaluation of ligand binding free energies by computational methods is still a very challenging active area of research. The most employed methods for these calculations can be roughly classified into four groups: (i) the fastest and less accurate methods, such as molecular docking, designed to sample a large number of molecules and rapidly rank them according to the potential binding energy; (ii) the second class of methods use a thermodynamic ensemble, typically generated by molecular dynamics, to analyze the endpoints of the thermodynamic cycle for binding and extract differences, in the so-called ‘end-point’ methods; (iii) the third class of methods is based on the Zwanzig relationship and computes the free energy difference after a chemical change of the system (alchemical methods); and (iv) methods based on biased simulations, such as metadynamics, for example. These methods require increased computational power and as expected, result in increased accuracy for the determination of the strength of binding. Here, we describe an intermediate approach, based on the Monte Carlo Recursion (MCR) method first developed by Harold Scheraga. In this method, the system is sampled at increasing effective temperatures, and the free energy of the system is assessed from a series of termsW(b, T), computed from Monte Carlo (MC) averages at each iteration. We show the application of the MCR for ligand binding with datasets of guest-hosts systems (N=75) and we observed that a good correlation is obtained between experimental data and the binding energies computed with MCR. We also compared the experimental data with an end-point calculation from equilibrium Monte Carlo calculations that allowed us to conclude that the lower-energy (lower-temperature) terms in the calculation are the most relevant to the estimation of the binding energies, resulting in similar correlations between MCR and MC data and the experimental values. On the other hand, the MCR method provides a reasonable view of the binding energy funnel, with possible connections with the ligand binding kinetics, as well. The codes developed for this analysis are publicly available on GitHub as a part of theLiBELa/MCLiBELaproject (https://github.com/alessandronascimento/LiBELa).