bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silent embolism of a large thrombus in transit through the patent foramen ovale: a case report
Authors: Hegde Shruti , Kabadi Mitesh , Johnstone Michael 
Published: March 2021

Abstract

Background
Detection of a thrombus in transit through a patent foramen ovale (PFO) is extremely rare due to the transient nature of the process. We report an unusual case of a large, paradoxical embolus in transit seen on echocardiography through a PFO that was not found upon atriotomy.

Case summary
An 80-year-old woman presented to the emergency room with shortness of breath and right leg pain. She was haemodynamically stable on presentation, and her physical exam was unremarkable. An ultrasound of her right leg revealed a deep vein thrombus in the posterior tibial vein, and chest computed tomography angiography showed saddle pulmonary emboli. Transthoracic echocardiogram identified a large thrombus in transit through a PFO, which was confirmed with a transoesophageal echocardiogram (TOE). She underwent an emergency embolectomy. The thrombus in transit was confirmed by TOE prior to bypass initiation; however, no thrombi were found in any chambers of the heart following atriotomy. Her postoperative recovery was uneventful. She had no focal neurological deficits or any apparent signs of large vessel embolization.

Discussion
Cases of silent embolism have been reported in the literature, although they are rare. To our knowledge, this is the first case of a large thrombus in transit through a PFO in an elderly female that was confirmed by an intra-operative TOE but could not be found following atriotomy, with no obvious clinical signs of embolization.
Joint effects of HPV-related knowledge and socio-demographic factors on HPV testing behaviour among females in Shenzhen
Authors: Lin Wei , Chen Bin , Hu Haiyan , Yuan Shixin , Wu Bo , Zhong Chuyan , Huang Weikang , Liu Zhihua , Wang Yueyun 
Published: March 2021

Abstract

Background
Limited population-based studies explore the utilization and associated barriers or facilitators to cervical cancer screening in China. We attempted to investigate the associations of socio-demographic factors, HPV specific knowledge with HPV testing behaviour in Shenzhen, China.

Methods
A citywide cross-sectional survey was conducted from January to June 2015 in Shenzhen city by using a multistage stratified cluster sampling method. Socio-demographic information, awareness and specific knowledge of HPV, practice of HPV testing, and HPV vaccination-related attitude were collected. Multivariate logistic regression model was used to analyse possible associations.

Results
Approximately one third of total 8639 women aged from 30 to 60 years old had ever received HPV testing. Overall, 67.6% of all participants demonstrated low knowledge level of HPV. High HPV knowledge level was significantly associated with HPV testing behaviour (odds ratio: 3.792, 95% confidence interval: 3.400–4.230). The impact of residence and education on testing behaviour only turned to be significant if women had low level of HPV knowledge (P for multiplicative interactions: 0.001 and &lt;0.001, respectively), whereas monthly income exerted promotion effects apparently among those with high knowledge level (P for multiplicative interaction: 0.037).

Conclusions
Our study revealed gaps in HPV knowledge and screening participation among Chinese women, and provided novel clues that women with high HPV knowledge level would be more appeal to involve in HPV testing behaviour. The influence of HPV-related knowledge on HPV testing also lies in the joint effects with socio-demographic factors, including residence, education and monthly income.
The adaptation of the ‘Healthcare Complaints Analysis Tool’ for general practice
Authors: O’Dowd Emily , Lydon Sinéad , O’Connor Paul 
Published: March 2021

Abstract

Background
Patient complaints about care in general practice are underutilized as a source of safety improvement data.

Objective
This study aimed to adapt a secondary care complaints analysis tool for use in general practice contexts and assess the validity, reliability and usability of the adapted tool.

Methods
The study was conducted in two phases. Phase A: The Healthcare Complaints Analysis Tool (HCAT) designed for use in secondary care was adapted for use in general practice using an iterative six-stage process. Phase B: Participants from key stakeholder groups [General practitioners (n = 5), complaints managers (n = 9), health service researchers (n = 4)]. Participants completed an online survey and analysed 20 fictionalized patient complaints using the adapted tool. Inter-rater reliability and agreement with a referent standard were analysed using Gwet’s AC1 statistic.

Results
Phase A: The HCAT was adapted to the Healthcare Complaints Analysis Tool (General Practice) [HCAT(GP)]. The HCAT(GP) tool consists of three domains (clinical, management and relationship problems), and seven categories. The HCAT(GP) had both content and face validity. Phase B: Inter-rater reliability was substantial for the HCAT(GP) categories (Gwet’s AC1 = 0.65). Within-group agreement on the seven HCAT(GP) categories was substantial to perfect (AC1 0.61–0.85). Participants had substantial to perfect agreement with the referent standard across the survey with a mean AC1 of 0.899 (Range 0.76–0.97).

Conclusions
This study reports the adaptation of the HCAT(GP) and has established that the tool has sufficient validity, reliability and usability. This adapted tool can be applied to general practice complaints to identify areas for improvement.
Gap and stand structural characteristics in a managed and an unmanaged old-growth oriental beech (Fagus orientalisLipsky) forest
Authors: Parhizkar Pejman , Sagheb-Talebi Khosro , Zenner Eric K , Hassani Majid , Sadeghzadeh Hallaj Mohammad Hosein 
Published: March 2021

AbstractSimplified forest structures following even-age management have been associated with the loss of biodiversity, which may be avoided through disturbance-inspired silviculture. Here, we ask how much do gap characteristics in a managed old-growth differ from those in unmanaged old-growth subject only to natural dynamics? In this study, we compared important characteristics of gaps (e.g. canopy gap fraction, distribution of gap sizes) and gapmakers (e.g. size classes, frequency, decay classes) between a managed and an adjacent unmanaged old-growth Oriental beech (Fagus orientalis Lipsky) compartment in the Keladarsht region of northern Iran 10 years after a single harvest entry using single-tree selection. Canopy openings &gt;100 m2 with visible remnants of gapmakers (i.e. stumps) were included in this study. Gap characteristics of both compartments were within typical ranges for old-growth beech. Nonetheless, small but potentially important differences between the two areas were observed. In the managed compartment, harvesting poor quality trees with structural defects and typical diameters at breast height &gt;52.5 cm plus natural mortality resulted in 102 canopy gaps (1–6 gapmakers, averaging 3.5 gaps/ha, gap fraction 9.8 per cent) compared with 59 natural canopy gaps (1–7 gapmakers, averaging 2.6 gaps/ha, gap fraction 13.7 per cent) in the unmanaged compartment. In both compartments, medium-sized gaps (200–500 m2) were most prevalent. In the managed compartment, 60 per cent of gapmakers were large or very large (typically cut) compared with 39 per cent in the unmanaged compartment where large trees typically snapped and became snags. Uprooting, particularly of small and medium sized gapmakers, was less common in the managed than the unmanaged compartment. Our results indicate that even one single-tree selection harvest may lead to a short-term divergence in stand structure compared with the unmanaged forest. While such managed forests may no longer be considered as old-growth, divergences in canopy gap characteristics indicate that a more nuanced harvesting scheme that includes cutting some larger gaps may more closely mimic the canopy dynamics of this old-growth forest.
Single-cell data clustering based on sparse optimization and low-rank matrix factorization
Authors: Hu Yinlei , Li Bin , Chen Falai , Qu Kun 
Published: March 2021

Abstract
Unsupervised clustering is a fundamental step of single-cell RNA-sequencing (scRNA-seq) data analysis. This issue has inspired several clustering methods to classify cells in scRNA-seq data. However, accurate prediction of the cell clusters remains a substantial challenge. In this study, we propose a new algorithm for scRNA-seq data clustering based on Sparse Optimization and low-rank matrix factorization (scSO). We applied our scSO algorithm to analyze multiple benchmark datasets and showed that the cluster number predicted by scSO was close to the number of reference cell types and that most cells were correctly classified. Our scSO algorithm is available at https://github.com/QuKunLab/scSO. Overall, this study demonstrates a potent cell clustering approach that can help researchers distinguish cell types in single- scRNA-seq data.
Simplified equations for lower crustal flow driven by lateral pressure gradients
Authors: Perry-Houts Jonathan , Humphreys Eugene 
Published: March 2021

SUMMARY
Evidence from seismology, geology and geodynamic studies suggests that regional-scale lower crustal flow occurs in many tectonic settings. Pressure gradients caused by mantle processes and crustal density heterogeneity can provide driving force for lower crustal flow. Numerically modelling such flow can be computationally expensive. However, by exploiting symmetry in the physical system, it is possible to represent the vertical component of flow in terms of its lateral components, thereby reducing the problem’s spatial dimension by one. Here, we present a mathematical formulation for flow in a viscous channel below an elastic upper plate, which is optimized for solution by common numerical methods. Our formulation drastically reduces the computational load required to simulate lower crustal flow over large areas and long timescales. We apply this model to two example problems, with and without an elastic upper plate, identifying combinations of parameters that are capable of generating measurable geologic uplift.
Spectrum of strong-motion records for large magnitude Chilean earthquakes
Authors: Rivera Efraín , Ruiz Sergio , Madariaga Raúl 
Published: March 2021

SUMMARYWe studied the broad-band spectra of the eight largest earthquakes that have occurred in Chile in the last 25 yr using strong-motion records and 1-Hz high-rate GNSS (cGNSS) data. To avoid the numerical instability problem with the double integration of the accelerograms, we computed velocity spectra integrating the acceleration time-series in the spectral domain and compared them to time-differentiated the cGNSS displacement records. To compute the velocity spectrum, we used a multitaper algorithm so as to provide stability over the entire spectral band. We found that the velocity spectra of records obtained close to the main rupture of the earthquakes are different from classical Aki and Brune spectra. The velocity spectrum of large events in Chile presents a flat trend at low frequencies produced by the near-field waves. This trend converges at low frequencies to the static displacement as determined from GNSS data. For different magnitude earthquakes, we observe a transition in the ground-velocity spectrum from a decay of ${f^{ - 1}}$ at high frequencies and a flat trend at low frequencies to a more classical model with a peak at the corner frequency. The source-station distance influences the shape of the velocity spectrum at low frequencies, but there is no simple rule for the records available at present. At intermediate frequencies, the spectra are controlled by surface waves and S waves. We found a transition in the velocity spectrum for the 2014 Iquique earthquake, which indicates a change in the decay of the spectrum for stations at distances greater than ∼200 km. Finally, we show that the flat low-frequency trend of the velocity spectra determined from accelerograms, and the peak ground-displacement (PGD) determined from GNSS data scales with the moment to the power 2/3.
Loss of ten-eleven translocation 2 induces cardiac hypertrophy and fibrosis through modulating ERK signaling pathway
Authors: Tao Huikang , Xu Weize , Qu Wenzheng , Gao Hui , Zhang Jinyu , Cheng Xuejun , Liu Ning , Chen Jinghai , Xu Guo-Liang , Li Xuekun , Shu Qiang 
Published: March 2021

Abstract
The ten-eleven translocation (Tet) family of dioxygenases convert 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC-mediated epigenetic modifications play essential roles in diverse biological processes and diseases. Here, we show that Tet proteins and 5hmC display dynamic features during postnatal cardiac development and that Tet2 is the predominant dioxygenase present in heart. Tet2 knockout results in abnormal cardiac function, progressive cardiac hypertrophy and fibrosis. Mechanistically, Tet2 deficiency leads to reduced hydroxymethylation in the cardiac genome and alters the cardiac transcriptome. Mechanistically, Tet2 loss leads to a decrease of Hspa1b expression, a regulator of the extracellular signal-regulated protein kinase (Erk) signaling pathway, which leads to over-activation of Erk signaling. Acute Hspa1b knock down (KD) increased the phosphorylation of Erk and induced hypertrophy of cardiomyocytes, which could be blocked by Erk signaling inhibitor. Consistently, ectopic expression of Hspa1b was able to rescue the deficits of cardiomyocytes induced by Tet2 depletion. Taken together, our study’s results reveal the important roles of Tet2-mediated DNA hydroxymethylation in cardiac development and function.
Spontaneous seizures and elevated seizure susceptibility in response to somatic mutation of sodium channel Scn8a in the mouse
Authors: Yu Wenxi , Smolen Corrine E , Hill Sophie F , Meisler Miriam H 
Published: March 2021

Abstract
De novo mutations of neuronal sodium channels are responsible for ~5% of developmental and epileptic encephalopathies, but the role of somatic mutation of these genes in adult-onset epilepsy is not known. We evaluated the role of post-zygotic somatic mutation by adult activation of a conditional allele of the pathogenic variant Scn8aR1872W in the mouse. After activation of CAG-Cre-ER by tamoxifen, the mutant transcript was expressed throughout the brain at a level proportional to tamoxifen dose. The threshold for generation of spontaneous seizures was reached when the proportion of mutant transcript reached 8% of total Scn8a transcript, equivalent to expression of the epileptogenic variant in 16% of heterozygous neurons. Expression below this level did not result in spontaneous seizures, but did increase susceptibility to seizure induction by kainate or auditory stimulation. The relatively high threshold for spontaneous seizures indicates that somatic mutation of sodium channels is unlikely to contribute to the elevated incidence of epilepsy in the elderly population. However, somatic mutation could increase susceptibility to other seizure stimuli.
mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion
Authors: Taylor Henry , Yerlioglu Dilay , Phen Claudia , Ballauff Antje , Nedelkopoulou Natalia , Spier Isabel , Loverdos Inés , Busoni Veronica B , Heise Jürgen , Dale Peter , de Meij Tim , Sweet Kevin , Cohen Marta C , Fox Victor L , Mas Emmanuel , Aretz Stefan , Eng Charis , Buderus Stephan , Thomson Mike , Rojas Isabel , Uhlig Holm H 
Published: March 2021

Abstract
Ultra-rare genetic disorders can provide proof of concept for efficacy of targeted therapeutics and reveal pathogenic mechanisms relevant to more common conditions. Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A). Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate. No effective pharmacological therapy exists. A multi-center cohort analysis was performed to characterize phenotype and investigate the therapeutic effect of mammalian target of rapamycin (mTOR) inhibition (adverse events, disease progression, time to colectomy and mortality) in patients with JPI. Among 25 JPI patients identified (mean age of onset 13 months), seven received mTOR inhibitors (everolimus, n = 2; or sirolimus, n = 5). Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07–0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077). Long-term mTOR inhibitor treatment was well tolerated over an accumulated follow-up time of 29.8 patient years. No serious adverse events were reported. Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI. Inhibition of the phosphoinositol-3-kinase–AKT–mTOR pathway mitigates the detrimental synergistic effects of combined PTEN–BMPR1A deletion. This is the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome.
Collecting New Peak and Intermediate Infliximab Levels to Predict Remission in Inflammatory Bowel Diseases
Authors: Liefferinckx Claire , Bottieau Jérémie , Toubeau Jean-François , Thomas Debby , Rahier Jean-François , Louis Edouard , Baert Filip , Dewint Pieter , Pouillon Lieven , Lambrecht Guy , Vallée François , Vermeire Severine , Bossuyt Peter , Franchimont Denis 
Published: March 2021

AbstractBackgroundThe loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction.MethodsThis was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30.ResultsInfliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%.ConclusionsThis study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients’ clinical management.
Light at Night and Disrupted Circadian Rhythms Alter Physiology and Behavior
Authors: Bumgarner Jacob R , Nelson Randy J 
Published: March 2021

Abstract
Life on earth has evolved during the past several billion years under relatively bright days and dark nights. Virtually all organisms on the planet display an internal representation of the solar days in the form of circadian rhythms driven by biological clocks. Nearly every aspect of physiology and behavior is mediated by these internal clocks. The widespread adoption of electric lights during the past century has exposed animals, including humans, to significant light at night (LAN) for the first time in our evolutionary history. Importantly, endogenous circadian clocks depend on light for synchronization with the external daily environment. Thus, LAN can derange temporal adaptations. Indeed, disruption of natural light–dark cycles results in several physiological and behavioral changes. In this review, we highlight recent evidence demonstrating how LAN exposure can have serious implications for adaptive physiology and behavior, including immune, endocrine, and metabolic function, as well as reproductive, foraging, and migratory behavior. Lastly, strategies to mitigate the consequences of LAN on behavior and physiology will be considered.
External validity and clinical usefulness of a risk prediction model for 30 day unplanned hospitalization in patients receiving outpatient parenteral antimicrobial therapy
Authors: Durojaiye Oyewole Christopher , Morgan Robin , Chelaghma Naziha , Palit Joyeeta , Keil Christopher , Omer Rasha , Cartwright Katharine , Kritsotakis Evangelos I 
Published: March 2021

Abstract

Objectives
Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a variety of infections. However, hospital readmissions remain relatively common. We examined the external validity and clinical usefulness of a previously derived risk prediction model for 30 day unplanned hospitalization in patients receiving OPAT.

Methods
A retrospective cohort study was conducted at two large teaching hospitals in the UK. The design comprised quasi-external temporal validation on patients from the same OPAT setting as the model development, and broader external validation on patients from a different setting. The model predictors were age, prior hospitalizations in the preceding 12 months, Charlson comorbidity score, concurrent IV antimicrobial therapy, type of infection and mode of OPAT treatment. Discriminative ability, calibration and clinical usefulness were assessed.

Results
Data from 2578 OPAT patients were analysed. The rates of 30 day unplanned hospitalization were 11.5% (123/1073), 12.9% (140/1087) and 25.4% (106/418) in the model derivation, temporal validation and broader external validation cohorts, respectively. The discriminative ability of the prediction model was adequate on temporal validation (c-statistic 0.75; 95% CI: 0.71–0.79) and acceptable on broader validation (c-statistic 0.67; 95% CI: 0.61–0.73). In both external cohorts, the model displayed excellent calibration between observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.

Conclusions
A simple risk prediction model for unplanned readmission in OPAT patients demonstrated reproducible predictive performance, broad clinical transportability and clinical usefulness. This model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care.