Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in ...supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1
SiglecF
transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Attention is a critical cognitive function, allowing humans to select, enhance, and sustain focus on information of behavioral relevance. Attention contains dissociable neural and psychological ...components. Nevertheless, some brain networks support multiple attentional functions. In this study, we used the visual attentional blink (VAB) as a test of the functional generalizability of the brain’s attentional networks. In a VAB task, attention devoted to a target often causes a subsequent item to be missed. Although frequently attributed to limitations in attentional capacity or selection, VAB deficits attenuate when participants are distracted or deploy attention diffusely. The VAB is also behaviorally and theoretically dissociable from other attention tasks. Here we used Connectome-based Predictive Models (CPMs), which associate individual differences in task performance with functional connectivity patterns, to test their ability to predict performance for multiple attentional tasks. We constructed visual attentional blink (VAB) CPMs, and then used them and a sustained attention network model (saCPM; Rosenberg et al., 2016a) to predict performance. The latter model had been previously shown to successfully predict performance across tasks involving selective attention, inhibitory control, and even reading recall. Participants (n = 73; 24 males) underwent fMRI while performing the VAB task and while resting. Outside the scanner, they completed other cognitive tasks over several days. A vabCPM constructed from VAB task data (behavior and fMRI) successfully predicted VAB performance. Strikingly, the network edges that predicted better VAB performance (positive edges) predicted worse performance for selective and sustained attention tasks, and vice versa. Predictions from applying the saCPM to the data mirrored these results, with the network’s negative edges predicting better VAB performance. The vabCPM’s positive edges partially yet significantly overlapped with the saCPM’s negative edges, and vice versa. Many positive edges from the vabCPM involved the default mode network, whereas many negative edges involved the salience/ventral attention network. We conclude that the vabCPM and saCPM networks reflect general attentional functions that influence performance on many tasks. The networks may indicate an individual’s propensity to deploy attention in a more diffuse or a more focused manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of ...coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.
This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.
Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant's decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation SD: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).
A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.
ChiCTR.org.cn, ChiCTR2100048080.
Background/Objective:
Traumatic intracranial hemorrhage (tICH) accounts for significant trauma morbidity and mortality. Several studies have developed prognostic models for tICH outcomes, but ...previous models face limitations, including poor generalizability and limited accuracy. The objective was to develop a prognostic model and determine predictors of mortality using the largest trauma database in the U.S., applying rigorous analytical methodology with true hold-out-set model validation.
Methods:
We identified 248,536 patients in the National Trauma Data Bank (NTDB) from 2012 to 2016 with a diagnosis code associated with tICH. For each admission, we collected demographic information, systolic blood pressure, blood alcohol level (BAL), Glasgow Coma Score (GCS), Injury Severity Score (ISS), presence of epidural/subdural/subarachnoid/intraparenchymal hemorrhage, comorbidities, complications, trauma center level, and trauma center region. Our final study population was 212,666 patients following exclusion of records with missing data. The dependent variable was patient death. Linear support vector machine (SVM) classification was carried out with recursive feature selection. Model performance was assessed using holdout 10-fold cross-validation.
Results:
Cross-validation demonstrated a mean accuracy of 0.792 (95% CI 0.783–0.799). Accuracy, precision, recall, and AUC were 0.827, 0.309, 0.750, and 0.791, respectively. In the final model, high ISS, advanced age, subdural hemorrhage, and subarachnoid hemorrhage were associated with increased mortality, while high GCS verbal and motor subscores, current smoker, BAL beyond the legal limit, and level 1 trauma center were associated with decreased mortality.
Conclusions:
A linear SVM model was developed for tICH, with nine features selected as predictors of mortality. These findings are applicable to multiple hemorrhage subtypes and may benefit the triage of high risk patients upon admission. While many studies have attempted to create models to predict mortality in TBI, we sought to confirm those predictors using modern modeling approaches, machine learning, and true hold-out test sets, using the largest available TBI database in the U.S. We find that while the predictors we identify are consistent with prior reports, overall prediction accuracy is somewhat lower than prior reports when assessed more rigorously.
New Findings
What is the central question of the study?
Are measures of reduced insulin sensitivity in young, normoglycaemic subjects correlated with near‐infrared spectroscopy‐derived microvascular ...responsiveness tissue oxygen saturation reperfusion rate (STO2 upslope) during postocclusive reactive hyperaemia?
What is the main finding and its importance?
A sevenfold range of hepatic insulin sensitivity is significantly correlated (r = 0.44, P = 0.02) with STO2 upslope after transient tissue ischaemia. Near‐infrared spectroscopy may be an important tool for determining altered microvascular function before onset of hyperglycaemia. Identification of pre‐type 2 diabetes much earlier than with the present clinical criteria is important for pre‐emptive measures against microvascular deterioration.
Near‐infrared spectroscopy (NIRS) measurement of postocclusive reactive hyperaemia (PORH) tissue oxygen saturation reperfusion rate STO2 upslope (as a percentage per minute) has recently been correlated with the percentage of flow‐mediated dilatation (%FMD). Cardiovascular disease is associated with impairments in %FMD. Reduced insulin sensitivity may negatively affect the vascular system for many years before prediabetes/type 2 diabetes states. The aim of this study was to determine whether static and dynamic STO2 parameters during PORH are correlated with reduced insulin sensitivity in young, normoglycaemic subjects. Glucose and insulin were measured during an oral glucose tolerance test in 18‐ to 26‐year‐old, healthy subjects (11 men and 11 women), and STO2 was measured during PORH of antebrachial muscle. Hepatic (ISIHOMA) and whole‐body (ISICOMP) insulin sensitivities were calculated. The STO2 upslope was negatively correlated with minimal STO2 (r = −0.5, P = 0.01). The change of STO2 from minimum to baseline (ΔSTO2) was significantly negatively correlated with fasting insulin (r = −0.5, P = 0.01) and a positively correlated with ISIHOMA (r = 0.65, P = 0.001). The minimum STO2 was significantly negatively correlated with ISIHOMA, and STO2 upslope was significantly positively correlated with ISIHOMA (r = 0.44, P = 0.02). The minimum STO2 (a measure of O2 extraction while the cuff was inflated), ΔSTO2 (a measure of the amount of reperfusion) and STO2 upslope (a measure of responsiveness of the microcirculation to ischaemia) were all positively correlated with ISIHOMA, one of the longest‐used measures of insulin sensitivity. The NIRS‐derived STO2 might be a useful tool for assessing how levels of reduced insulin sensitivity in young, normoglycaemic adults affect the microvasculature.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•A novel method to examine saccade plans during free viewing is proposed.•Saccade plans can overlap in time during the free-viewing of images.•Saccade plans can be cancelled before they are completed ...during free viewing.
In the current study, we examined how the saccadic system responds when visual information changes dynamically in our environment. Previous studies, using the double-step task, have shown that (a) saccade plans could overlap, such that saccade preparation to an object started even while the saccade preparation to another object was ongoing, and (b) saccade plans could be cancelled before they were completed. In these studies, saccade targets were restricted to a few, experimenter-defined locations. Here, we examined whether saccade plan overlap and cancellation mechanisms could be observed in free-viewing conditions. For each trial, we constructed sets of two images, each containing five objects. All objects have unique positions. Image 1 was presented for several fixations, before Image 2 was presented during a fixation, presumably while a saccade plan to an object in Image 1 was ongoing. There were two crucial findings: (a) First, the saccade immediately following the transition was sometimes executed towards objects in Image 2, and not an object in Image 1, suggesting that the earlier saccade plan to an Image 1 object had been cancelled. Second, analysis of the temporal data also suggested that preparation of the first post-transition saccade started before an earlier saccade plan to an Image 1 object was executed, implying that saccade plans overlapped.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients infected with SARS-CoV-2 may deteriorate rapidly and therefore continuous monitoring is necessary. We conducted an observational study involving patients with mild COVID-19 to explore the ...potentials of wearable biosensors and machine learning-based analysis of physiology parameters to detect clinical deterioration. Thirty-four patients (median age: 32 years; male: 52.9%) with mild COVID-19 from Queen Mary Hospital were recruited. The mean National Early Warning Score 2 (NEWS2) were 0.59 ± 0.7. 1231 manual measurement of physiology parameters were performed during hospital stay (median 15 days). Physiology parameters obtained from wearable biosensors correlated well with manual measurement including pulse rate (r = 0.96, p < 0.0001) and oxygen saturation (r = 0.87, p < 0.0001). A machine learning-derived index reflecting overall health status, Biovitals Index (BI), was generated by autonomous analysis of physiology parameters, symptoms, and other medical data. Daily BI was linearly associated with respiratory tract viral load (p < 0.0001) and NEWS2 (r = 0.75, p < 0.001). BI was superior to NEWS2 in predicting clinical worsening events (sensitivity 94.1% and specificity 88.9%) and prolonged hospitalization (sensitivity 66.7% and specificity 72.7%). Wearable biosensors coupled with machine learning-derived health index allowed automated detection of clinical deterioration.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Spontaneous splenic rupture is a rare but life-threatening complication of Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). It occurs in less than 0.5% of cases and is the most ...frequent cause of death in IM. We report a case of a 13-year old female presenting with hemodynamic instability following diagnosis of EBV-induced IM. Abdominal CT was positive for grade III splenic laceration with active extravasation and exploratory laparotomy with splenectomy was performed. Postoperatively, she recovered appropriately, received vaccinations, and was discharged on postoperative day 5. Follow up has revealed no complications and return to normal activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endoluminal closure of gastrogastric fistula Wu, Esther; Garberoglio, Renzo; Scharf, Keith
Surgery for obesity and related diseases,
03/2016, Volume:
12, Issue:
3
Journal Article
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