bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Associations Between Cumulative Effects of Blood Pressure From Childhood to Adulthood and Adult Subclinical Renal Damage: Hanzhong Adolescent Hypertension Cohort Study
Authors: Liao Yue-yuan , Yang Jun , Yang Rui-hai , Mu Jian-jun 
Published: February 2023

Abstract

Background
To investigate the impact of cumulative effects of systolic and diastolic blood pressures (SBP and DBP) from childhood to adulthood on adult subclinical renal damage (SRD).

Methods
A baseline survey on height, bodyweight, and blood pressure (BP) of 6- to 15-year-old school students in Hanzhong, Shaanxi, was conducted in 1987. Follow-up was conducted in 1989, 1992, 1995, 2005, 2013, and 2017. A total of 1,553 individuals who had been followed at least 4 times since baseline were included in the study. Blood and urine biochemical indexes were detected during the follow-up period. Renal function was assessed with estimated glomerular filtration rate and urine albumin-to-creatinine ratio. The logistic regression analysis was used to analyze the relationships between cumulative effects or longitudinal trends of BP and adult SRD.

Results
The proportion of adult SRD in the groups with high BP cumulative effects or longitudinal trends was significantly higher than that in the normal group (cumulative effects: SBP 20.6% vs. 10.3%, P &lt; 0.001 and DBP 22.2% vs. 9.8%, P &lt; 0.001; longitudinal trends: SBP 17.8% vs. 11.2%, P = 0.001 and DBP 19.1% vs. 10.8%, P &lt; 0.001). Multivariate logistic regression showed that the risk of adult SRD in the group with high BP cumulative effects (SBP: OR = 2.07, 95% CI 1.45–2.96, P &lt; 0.001; DBP: OR = 2.25, 95% CI 1.59–3.19, P &lt; 0.001) or high BP longitudinal trends (SBP: OR = 1.43, 95% CI 1.00–2.05, P = 0.049; DBP: OR = 1.50, 95% CI 1.05–2.13, P = 0.026) was significantly higher than that in the normal group, after adjusting for gender, age, body mass index, blood glucose, blood lipid, uric acid and other confounding factors.

Conclusions
The cumulative effects and longitudinal trends of BP from children to adults significantly increase the risk of adult SRD. Monitoring and controlling BP from childhood is important for long-term kidney health.
RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis
Authors: Rafiee Mahmoud-Reza , Rohban Sara , Davey Karen , Ule Jernej , Luscombe Nicholas M 
Published: February 2023

Abstract
Valosin-containing protein (VCP) is a hexameric ATPase associated with diverse cellular activities. Genetic mutations in VCP are associated with several forms of muscular and neuronal degeneration, including amyotrophic lateral sclerosis (ALS). Moreover, VCP mediates UV-induced proteolysis of RNA polymerase II (RNAPII), but little is known about the effects of VCP mutations on the transcriptional machinery. Here, we used silica particle-assisted chromatin enrichment and mass spectrometry to study proteins co-localized with RNAPII in precursor neurons differentiated from VCP-mutant or control induced pluripotent stem cells. Remarkably, we observed diminished RNAPII binding of proteins involved in transcription elongation and mRNA splicing in mutant cells. One of these is SART3, a recycling factor of the splicing machinery, whose knockdown leads to perturbed intron retention in several ALS-associated genes. Additional reduced proteins are RBM45, EIF5A and RNF220, mutations in which are associated with various neurodegenerative disorders and are linked to TDP-43 aggregation. Conversely, we observed increased RNAPII binding of heat shock proteins such as HSPB1. Together, these findings shed light on how transcription and splicing machinery are impaired by VCP mutations, which might contribute to aberrant alternative splicing and proteinopathy in neurodegeneration.
Depression mediated the relationships between precentral-subcortical causal links and motor recovery in spinal cord injury patients
Authors: Li Yan , Zhang Yang , Zhou Weiqi , Li Rong , Yu Jiali , Gong Lisha , Leng Jinsong , Lu Fengmei , Hou Jingming , Chen Huafu , Gao Qing 
Published: February 2023

Abstract
Depression after brain damage may impede the motivation and consequently influence the motor recovery after spinal cord injury (SCI); however, the neural mechanism underlying the psychological effects remains unclear. This study aimed to examine the casual connectivity changes of the emotion-motivation-motor circuit and the potential mediating effects of depression on motor recovery after SCI. Using the resting-state functional magnetic resonance imaging data of 35 SCI patients (24 good recoverers, GR and 11 poor recoverers, PR) and 32 healthy controls (HC), the results from the conditional Granger causality (GC) analysis demonstrated that the GR group exhibited sparser emotion-motivation-motor GC network compared with the HC and PR groups, though the in−/out-degrees of the emotion subnetwork and the motor subnetwork were relatively balanced in the HC and GR group. The PR group showed significantly inhibitory causal links from amygdala to supplementary motor area and from precentral gyrus to nucleus accumbens compared with GR group. Further mediation analysis revealed the indirect effect of the 2 causal connections on motor function recovery via depression severity. Our findings provide further evidence of abnormal causal connectivity in emotion-motivation-motor circuit in SCI patients and highlight the importance of emotion intervention for motor function recovery after SCI.
The role of magnetic sphincter augmentation in the gastroesophageal reflux disease treatment pathway: the gastroenterology perspective
Authors: Patel Amit , Gyawali C Prakash 
Published: February 2023

Abstract
Magnetic sphincter augmentation (MSA) is a surgical intervention for well-characterized gastroesophageal reflux disease (GERD), where the esophagogastric junction barrier is augmented using a bracelet of magnetized titanium beads. MSA could be an attractive option for patients with documented GERD who wish to avoid long-term pharmacologic therapy or whose symptoms are not adequately managed with lifestyle modifications and pharmacologic therapy. The ‘ideal’ MSA patient is one with prominent regurgitation, without dysphagia or esophageal motor dysfunction, with objective evidence of GERD on upper endoscopy and/or ambulatory reflux monitoring. Appropriate candidates with significant hiatus hernia may pursue MSA with concomitant hiatus hernia repair. The increasing adoption of MSA in the GERD treatment pathway reflects research that shows benefits in long-term outcomes and healthcare costs compared with other established therapies in appropriate clinical settings.
Use of transoesophageal echocardiography to detect and manage atrial thrombi in light-chain cardiac amyloidosis: a case report
Authors: Dang Toan Quang , Hoang Sy Van 
Published: February 2023

Abstract

Background
Increased intracardiac thrombus formation in light-chain cardiac amyloidosis (AL-CA) has been associated with thrombotic events such as stroke and high rates of mortality and morbidity.

Case summary
A 51-year-old man was admitted to the emergency department with a sudden change in consciousness. His emergency brain magnetic resonance imaging showed two foci of cerebral infarction on the bilateral temporal lobes. His electrocardiogram displayed a normal sinus rhythm with low QRS voltage. Transthoracic echocardiography showed concentric thickened ventricles, dilatation of both atria, a left ventricular ejection fraction of 53%, and a Grade 3 diastolic dysfunction. The bull-eye plot on speckle tracking echocardiography displayed a distinctive apical sparing pattern. A serum-free immunoglobulin analysis showed increased lambda-free light chains (295.59 mg/L) with a reduced kappa/lambda ratio (0.08). Light-chain amyloidosis was subsequently confirmed by examining the histology of the abdominal fat-pad tissue. On transoesophageal echocardiography (TEE), an elongated static thrombus and a mobile bouncing oval thrombus were found on the left and right atrial appendages, respectively. Atrial thrombi were managed with a full dose of dabigatran of 150 mg twice daily, which resulted in a complete resolution after 2 months of TEE follow-up.

Discussion
Complicating intracardiac thrombosis has been considered one of the major contributions of death in cardiac amyloidosis. Transoesophageal echocardiography should be established to aid in the detection and management of atrial thrombus in AL-CA.
A ‘potential motherhood’ penalty? A longitudinal analysis of the wage gap based on potential fertility in Germany and the United Kingdom
Authors: Zamberlan Anna , Barbieri Paolo 
Published: February 2023

AbstractWhile labour market penalties related to motherhood are a widely studied topic, less is known about the implications of signalled potential fertility. We thus posed the question of whether potential fertility—operationalized as the likelihood that a childless woman will transition to motherhood depending on observed sociodemographic characteristics—is associated with a wage penalty and—if so—what the drivers of this wage gap are. We further tested theory-driven hypotheses about heterogeneity across institutional contexts (i.e. in Germany and the United Kingdom) and socio-economic classes. In so doing, we relied on SOEP, BHPS, and UKHLS panel data to construct a synthetic measure of potential fertility over the period from 1991 to 2017. We first explored the overall association between potential fertility and wages and found a wage gap to the disadvantage of potential mothers in both contexts, albeit with non-negligible heterogeneity across time and socio-economic classes. Subsequently, we selected the top and bottom quartiles of the distribution of potential fertility and performed a 2-fold decomposition of the wage differential between potential mothers and women who are less likely to transition to motherhood. The observed wage gap can mostly be explained by compositional differences in observed characteristics between the two groups of women, thereby leaving little room for explanations based on employer discrimination.
The impacts of reducing atmospheric and oceanic de-aliasing model error on temporal gravity field model determination
Authors: Zhou Hao , Zheng Lijun , Pail Roland , Liu Shuhao , Qing Tiantian , Yang Fan , Guo Xiang , Luo Zhicai 
Published: February 2023

SUMMARYThe Gravity Recovery and Climate Experiment (GRACE) and its successor GRACE Follow-On mission have been estimating temporal gravity field models for various geoscience applications since 2002. While the errors in atmospheric and oceanic de-aliasing (AOD) model are still the key limitation for GRACE-type missions especially taking advantages of improved laser ranging interferometer (LRI), this paper explores the realistic assumption of continuously reducing AOD model error in global scale and regional scale (e.g. ocean, Greenland, Qinghai-Tibet plateau and South America) in the anticipated future. For this, using a realistic orbit scenario and error assumptions both for instrument and background model errors, the 5-yr full-scale simulations are implemented in the context of 26 scenarios with different AOD model errors. Our overall simulation results demonstrate that: (1) when the AOD model errors are reduced in the global scale, the corresponding gain in temporal gravity field determination is significant, with the cumulative geoid height error decrease from 11.28 to 6.25 mm in spectral domain, as well as 26.3–65.2 per cent noise reduction in terms of mean RMS residuals over ocean in spatial domain. (2) When the AOD model errors are reduced in the regional scale, the improvements of temporal gravity field estimations are diverse in different simulation scenarios. The most notable noise reduction, with 22.9–43.9 per cent noise reduction in spatial domain, is observed when the AOD model error decreases in ocean. The limited noise reductions (0.1 per cent and 1.3 per cent respectively in spectral and spatial domain) are observed in the temporal gravity field estimations if the AOD model is refined in other typical regions such as the Qinghai-Tibet plateau, the Greenland and the South America. (3) However, when the satellites passing over the AOD model refined regions, the along-orbit range rate analysis indicates that, there are visible differences by about 50.0 nm s−1 in terms of range rate residuals as well as 11.0–48.5 nm s−1 in terms of the mean RMS of range rate residuals. These results reflect the benefits of reducing AOD model error in both global and regional scale for improving GRACE-type temporal gravity estimation, especially considering the development of LRI technology.
Interplay between APP and glypican-1 processing and α-synuclein aggregation in undifferentiated and differentiated human neural progenitor cells
Authors: Cheng Fang , Fransson Lars-Åke , Mani Katrin 
Published: February 2023

Abstract
In Parkinson’s disease, there is an accumulation of α-synuclein (SYN) aggregates in neurons, which is promoted by neuroinflammation. In neural cells, cytokine-induced SYN aggregation is modulated by heparan sulfate (HS) derived from glypican-1 (GPC1) by amyloid precursor protein (APP) and nitric oxide (NO)-dependent cleavage. We have explored possible interplay between APP, GPC1, and SYN in undifferentiated and differentiated neural progenitor cells (NPCs) by modulating APP and GPC1 processing. Effects were monitored by immunofluorescence microscopy and slot immunoblotting using antibodies recognizing APP degradation products, HS released from GPC1, and SYN aggregates (filamentous SYN [SYNfil]). Suppression of HS release from GPC1 by inhibition of β-secretase or by NO deprivation resulted in no or slight increase in SYNfil aggregation. Stimulation of HS release by ascorbate did not further increase SYNfil staining. Interleukin-6 (IL-6) induced increased APP and GPC1 processing and SYNfil formation, which was reduced when β-secretase was inhibited and when HS release was impeded by NO deprivation. Ascorbate restored APP and GPC1 processing but did not affect SYNfil formation. Ascorbate-dependent differentiation of NPC resulted in the expression of tyrosine hydroxylase (TH) which colocalized with SYNfil. Suppression of APP processing by inhibition of β-secretase greatly disturbed the differentiation process. IL-6 induced coclustering of APP-degradation products, TH, HS, and SYNfil, which could be reversed by stimulation of HS release from GPC1 by excess ascorbate. We suggest that continuous release of HS from GPC1 moderates SYN aggregation and supports differentiation of NPC to dopaminergic neurons.
Assumptions and analysis planning in studies with missing data in multiple variables: moving beyond the MCAR/MAR/MNAR classification
Authors: Lee Katherine J , Carlin John B , Simpson Julie A , Moreno-Betancur Margarita 
Published: February 2023

Abstract
Researchers faced with incomplete data are encouraged to consider whether their data are ‘missing completely at random’ (MCAR), ‘missing at random’ (MAR) or ‘missing not at random’ (MNAR) when planning their analysis. However, there are two major problems with this classification as originally defined by Rubin in the 1970s. First, when there are missing data in multiple variables, the plausibility of the MAR assumption is difficult to assess using substantive knowledge and is more stringent than is generally appreciated. Second, although MCAR and MAR are sufficient conditions for consistent estimation with specific methods, they are not necessary conditions and therefore this categorization does not directly determine the best approach for handling the missing data in an analysis. How best to handle missing data depends on the assumed causal relationships between variables and their missingness, and what these relationships imply in terms of the ‘recoverability’ of the target estimand (the population parameter that encodes the answer to the underlying research question). Recoverability is defined as whether the estimand can be consistently estimated from the patterns and associations in the observed data without needing to invoke external information on the extent to which the distribution of missing values might differ from that of observed values. In this manuscript we outline an approach for deciding which method to use to handle multivariable missing data in an analysis, using directed acyclic graphs to depict missingness assumptions and determining the implications in terms of recoverability of the target estimand.
Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345 000 men and women aged 20–79 years
Authors: Mørland Jørg G , Magnus Per , Vollset Stein Emil , Leon David A , Selmer Randi , Tverdal Aage 
Published: February 2023

Abstract

Background
Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied.

Methods
A total of 344 556 individuals (20–79 years, 52 % women) recruited from population-based health screening during 1985–2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of &lt;30, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, 90–99 and &gt;99 mg/dl (&lt; 0.78, 0.78–1.01, 1.04–1.27, 1.30–1.53, 1.55–1.79, 1.81–2.04, 2.07–2.31, 2.33–2.56, &gt;2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health.

Results
During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50–59 mg/dl (1.30–1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels &gt;99 mg/dl (&gt;2.56 mmol/L) were 1.32 (1.21–1.43), 1.05 (0.89–1.24), 1.26 (1.09–1.46) and 1.68 (1.48–1.90) for all–cause, CVD, cancer and non–CVD/non–cancer mortality, respectively. For HDL-C levels &lt;30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24–1.36), 1.55 (1.44–1.67), 1.14 (1.05–1.23) and 1.19 (1.10–1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes.

Conclusions
Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.
The Global Well-Posedness and Decay Estimates for the 3D Incompressible MHD Equations With Vertical Dissipation in a Strip
Authors: Lin Hongxia , Suo Xiaoxiao , Wu Jiahong 
Published: February 2023

Abstract
The three-dimensional incompressible magnetohydrodynamic (MHD) system with only vertical dissipation arises in the study of reconnecting plasmas. When the spatial domain is the whole space $\mathbb R^3$, the small data global well-posedness remains an extremely challenging open problem. The one-directional dissipation is simply not sufficient to control the nonlinearity in $\mathbb R^3$. This paper solves this open problem when the spatial domain is the strip $\Omega := \mathbb R^2\times [0,1]$ with Dirichlet boundary conditions. By invoking suitable Poincaré type inequalities and designing a multi-step scheme to separate the estimates of the horizontal and the vertical derivatives, we are able to establish the global well-posedness in the Sobolev setting $H^3$ as long as the initial horizontal derivatives are small. We impose no smallness condition on the vertical derivatives of the initial data. Furthermore, the $H^3$-norm of the solution is shown to decay exponentially in time. This exponential decay is surprising for a system with no horizontal dissipation. This large-time behavior reflects the smoothing and stabilizing phenomenon due to the interaction within the MHD system and with the boundary.
Development of an optimized and practical pharmacokinetics/pharmacodynamics analysis method for aztreonam/nacubactam against carbapenemase-producingK. pneumoniae
Authors: Igarashi Yuki , Takemura Wataru , Liu Xiaoxi , Kojima Nana , Morita Takumi , Chuang Victor Tuan Giam , Enoki Yuki , Taguchi Kazuaki , Matsumoto Kazuaki 
Published: February 2023

AbstractBackgroundNacubactam, a new β-lactamase inhibitor with antibacterial activity, is being developed as a single drug to be co-administered with cefepime or aztreonam. However, determining pharmacokinetics/pharmacodynamics (PK/PD) parameters in β-lactam/β-lactamase inhibitor combinations remains challenging. We aimed to establish a practical PK/PD analysis method for aztreonam/nacubactam that incorporates instantaneous MIC (MICi).MethodsBased on chequerboard MIC measurements, MICi of aztreonam against carbapenemase-producing Klebsiella pneumoniae in the presence of nacubactam was simulated.ResultsThe mean change in the bacterial count of thigh-infected mice in an in vivo PD study was plotted based on %fT&gt;MICi and analysed using the inhibitory effect sigmoid Imax model. fT&gt;MICi calculated from the PK experiments showed a high correlation with the in vivo bactericidal effect, suggesting that fT&gt;MICi is the optimal PK/PD parameter for aztreonam/nacubactam. The target values of fT&gt;MICi achieving growth inhibition, 1 log10 kill and 2 log10 kill, were 22, 38% and 75%, respectively.ConclusionsThe PK/PD analysis method proposed in this study is promising for determining practical PK/PD parameters in combination therapy. In addition, this is the first report of aztreonam/nacubactam showing a potent in vivo therapeutic effect against NDM-producing K. pneumoniae.