Miracle-dz/UniFAR-FTUs huggingface dataset:
Reliability of CT‐based texture features: Phantom study

Abstract Objective To determine the intra‐, inter‐ and test‐retest variability of CT‐based texture analysis (CTTA) metrics. Materials and methods In this study, we conducted a series of CT imaging experiments using a texture phantom to evaluate the performance of a CTTA panel on routine abdominal imaging protocols. The phantom comprises of three different regions with various textures found in tumors. The phantom was scanned on two CT scanners viz. the Philips Brilliance 64 CT and Toshiba Aquilion Prime 160 CT scanners. The intra‐scanner variability of the CTTA metrics was evaluated across imaging parameters such as slice thickness, field of view, post‐reconstruction filtering, tube voltage, and tube current. For each scanner and scanning parameter combination, we evaluated the performance of eight different types of texture quantification techniques on a predetermined region of interest (ROI) within the phantom image using 235 different texture metrics. We conducted the repeatability (test‐retest) and robustness (intra‐scanner) test on both the scanners and the reproducibility test was conducted by comparing the inter‐scanner differences in the repeatability and robustness to identify reliable CTTA metrics. Reliable metrics are those metrics that are repeatable, reproducible and robust. Results As expected, the robustness, repeatability and reproducibility of CTTA metrics are variably sensitive to various scanner and scanning parameters. Entropy of Fast Fourier Transform‐based texture metrics was overall most reliable across the two scanners and scanning conditions. Post‐processing techniques that reduce image noise while preserving the underlying edges associated with true anatomy or pathology bring about significant differences in radiomic reliability compared to when they were not used. Conclusion Following large‐scale validation, identification of reliable CTTA metrics can aid in conducting large‐scale multicenter CTTA analysis using sample sets acquired using different imaging protocols, scanners etc.
Deficits in Enrichment-Dependent Neurogenesis and Enhanced Anxiety Behaviors Mediated by Expression of Alzheimer's Disease-Linked Ps1 Variants Are Rescued by Microglial Depletion

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that presently affects an estimated 5.7 million Americans. Understanding the basis for this disease is key for the development of a future successful treatment. In this effort, we previously reported that mouse prion protein-promoter-driven, ubiquitous expression of familial AD (FAD)-linked human PSEN1 variants in transgenic mice impairs environmental enrichment (EE)-induced proliferation and neurogenesis of adult hippocampal neural progenitor cells (AHNPCs) and in a non-cell autonomous manner. These findings were confirmed in PS1M146V/+ mice that harbor an FAD-linked mutation in the endogenous PSEN1 gene. We now demonstrate that CSF1R antagonist-mediated microglial depletion in transgenic male mice expressing mutant presenilin 1 (PS1) or PS1M146V/+ “knock-in” mice leads to a complete rescue of deficits in proliferation, differentiation and survival of AHNPCs. Moreover, microglia depletion suppressed the heightened baseline anxiety behavior observed in transgenic mice expressing mutant PS1 and PS1M146V/+ mice to levels observed in mice expressing wild-type human PS1 or nontransgenic mice, respectively. These findings demonstrate that in mice expressing FAD-linked PS1, microglia play a critical role in the regulation of EE-dependent AHNPC proliferation and neurogenesis and the modulation of affective behaviors. SIGNIFICANCE STATEMENT Inheritance of mutations in genes encoding presenilin 1 (PS1) causes familial Alzheimer's disease (FAD). Mutant PS1 expression enhances the levels and assembly of toxic Aβ42 peptides and impairs the self-renewal and neuronal differentiation of adult hippocampal neural progenitor cells (AHNPCs) following environmental enrichment (EE) that is associated with heightened baseline anxiety. We now show that microglial depletion fully restores the EE-mediated impairments in AHNPC phenotypes and suppresses the heightened baseline anxiety observed in mice expressing FAD-linked PS1. Thus, we conclude that the memory deficits and anxiety-related behaviors in patients with PS1 mutations is a reflection not just of an increase in the levels of Aβ42 peptides, but to impairments in the self-renewal and neuronal differentiation of AHNPCs that modulate affective behaviors.
Who benefits from mindfulness? The moderating role of personality and social norms for the effectiveness on psychological and physiological outcomes among police officers.

There is a growing interest to use mindfulness-based interventions (MBIs) for occupational health promotion. As most evidence for the beneficial effects comes from convenience samples in the social/education/health sector, it is still an open question if MBIs are effective in other contexts, or for whom MBIs are more effective. In addition, self-selection and sample characteristics may have biased previous findings. Theoretically and practically, it is important to know whether MBIs are also effective for nonselective samples outside the social and health sector, especially in agentic and male-oriented cultures. Therefore, this study investigates the effects of a MBI on physiological and psychological criteria in a nonselective sample of police officers. Moreover, this study examines whether effectiveness depends on participants' personality (neuroticism, openness, and conscientiousness) and on perceived social norms toward MBIs. Using a pre-post intervention design, N = 267 police officers were randomly assigned to an intervention group receiving a 6-week intervention and to a control group. Repeated-measures analysis of variance showed a positive effect on heart rate variability and a stronger reduction of psychological strain, health complaints, and negative affect, as well as more improvement of mindfulness and self-care in the intervention group in comparison with the control group. Additionally, participants higher in neuroticism and openness benefitted more, and the effectiveness was stronger for those who perceived a favorable social norm toward MBIs. Our findings provide evidence that participants with male-oriented occupations may also benefit from a MBI. The importance of individual differences and the social context is discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Complicated pneumonia in children

Educational aims To understand the pathogenesis of complicated community-acquired pneumonia in children To gain an understanding into the management of common complications of community-acquired pneumonia in children Summary Community-acquired pneumonia is a common paediatric infection and, even with the introduction of pneumococcal and Haemophilus vaccinations, most children will experience at least one episode before adult life. Most cases are self-limiting but a small number of children will develop sequelae and require hospitalisation. This review focuses on the presentation and management of complications of community-acquired pneumonia in children.
Diet Quality in Association with All-Cause, Cardiovascular, and Cancer Mortality Among US Adults: NHANES 1999-2010 (OR14-04-19).

Objectives The 2015 Dietary Guidelines for Americans (DGA) recommend a healthy eating pattern for chronic disease prevention. This study aimed to prospectively evaluate diet quality by adherence to the 2015 DGA in association with mortality outcomes among a representative sample of US adults. Methods Using dietary data collected by 24-hour diet recalls among 29,098 US adults aged 20+ years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2010, we estimated adherence to the 2015 DGA using the Healthy Eating Index-2015 (HEI-2015). Mortality from all cause, cardiovascular diseases (CVD), and cancer were obtained from linkage to the National Death Index Mortality data. Cox proportional-hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after multivariable adjustments. Results The mean (SE) of total HEI-2015 was 50.1 (0.2). During a median follow-up of 6.2 years, 2861 total deaths occurred, including 726 CVD and 671 cancer deaths. Compared to individuals in the lowest quartile of HEI-2015, those in the highest quartile had a 16% lower risk of all-cause mortality (Q4 vs. Q1: HR = 0.84; 95% CI: 0.72-0.90; P-trend = 0.04) and a 31% lower risk of cancer mortality (Q4 vs. Q1: HR = 0.69; 95% CI: 0.50-0.95; P-trend = 0.06). The lower all-cause and cancer mortality among those with higher HEI-2015 scores was confined to individuals with comorbidity conditions at baseline (all-cause mortality: Q4 vs. Q1: HR = 0.79; 95% CI: 0.67-0.94; p-trend = 0.005; cancer mortality: Q4 vs. Q1: HR = 0.46; 95% CI: 0.30-0.69; p-trend = 0.001), former smokers (all-cause mortality: Q4 vs. Q1: HR = 0.65; 95% CI: 0.49-0.88; p-trend = 0.006; cancer mortality: Q4 vs. Q1: HR = 0.47; 95% CI: 0.29-0.74; p-trend = 0.005), and those with a body mass index of 18.5-25 kg/m2 (all-cause mortality: Q4 vs. Q1: HR = 0.60; 95% CI: 0.46-0.79; p-trend < 0.001; cancer mortality: Q4 vs. Q1: HR = 0.40; 95% CI: 0.22-0.70; p-trend = 0.001). Similar associations were found between men and women. No significant associations were observed between HEI-2015 and CVD mortality. Conclusions Better adherence to the 2015 Dietary Guidelines of Americans is associated with lower all-cause and cancer mortality among US adults. Funding Sources National Institute of Health/National Institute of Minority Health and Health Disparities. Supporting Tables Images and/or Graphs
Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open‐label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty‐four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%‐100%). The patient who did not achieve SVR12 was a 4‐year‐old who discontinued treatment after 3 days because of “abnormal drug taste. ” The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3‐year‐old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.
Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis

Objectives Previous studies have demonstrated a strong latitudinal gradient in multiple sclerosis (MS) prevalence. Herein, we present a meta-analysis of the latitudinal gradient of MS prevalence including studies published since our 2011 review, seeking to assess the latitudinal gradient and whether it has changed since our previous analysis. Methods Studies published up to December 2018 were located via Embase, Web of Knowledge and PubMed, using standardised search terms; data were extracted from peer-reviewed studies and these studies added to those from our previous analysis. Where age-specific data were available, prevalence estimates were age-/sex-standardised to the 2009 European population. Prevalence estimates were adjusted for study prevalence year and ascertainment methods. The latitudinal association with MS prevalence was assessed by meta-regression. Results A total of 94 studies met inclusion criteria, yielding 230 new prevalence points and 880 altogether with those from the prior study. There was a significant positive gradient in time-corrected MS prevalence with increasing latitude (5.27/100 000 per degree latitude), attenuating slightly to 4.34/100 000 on age-standardisation, these associations persisting on adjustment for ascertainment method. Of note, the age-standardised gradient was consistently significantly enhanced from our previous study, regardless of whether it was as-measured, time-corrected or adjusted for ascertainment methods. Certain areas, such as the Scandinavian and Atlantic Coast/Central Europe regions, showed changes in MS prevalence gradient over time, but other regional gradients were similar. Conclusions This new meta-analysis confirms that MS prevalence is still strongly positively associated with increasing latitude and that the gradient is increasing, suggesting that potentially modifiable environmental factors, such as sun exposure, are still strongly associated with MS risk.
The Pitt Bacteremia Score Predicts Mortality in Non-Bacteremic Infections.

BACKGROUND Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSI). Here, we determined whether the PBS predicts 14-day inpatient mortality in non-bacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections. METHODS Patients were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS. RESULTS In a cohort of 475 patients with CRE infections, a PBS ≥ 4 was associated with mortality in patients with non-bacteremia infections (RR=21.9 [95% CI: 7.0, 68.8]) and with BSI (RR=6.0 [95% CI: 2.5, 14.4]). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature < 36.0ᴼ C versus ≥ 36ᴼ C was independently associated with mortality. A qPitt score ≥ 2 had similar discrimination as a PBS ≥ 4 in non-bacteremia infections. CONCLUSION Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in non-bacteremia CRE infections.
Print enhancement for eccentric vision

Image magnification is a well known means for print enhancement. However, a too large magnification hampers reading because of the decreased field of view. For certain patients with maculopathies, it has recently been reported that by using individualized compensation filters, less magnification is needed and higher reading rates are achieved. In this paper the possibilities of print enhancement for eccentric vision are explored further by using subjective estimates of image quality. The obtained results suggest that for two-tone text, image enhancement through spatial filtering, only makes sense in situations where the available contrast range is not entirely used.
A decade of clinical development of PARP inhibitors in perspective

Abstract Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce tumour-specific vulnerabilities that can be exploited therapeutically. In 2009, a first-in-man clinical trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib clinically validated the synthetic lethal interaction between inhibition of PARP1, a key sensor of DNA damage, and BRCA1/BRCA2 deficiency. In this review, we summarize a decade of PARP inhibitor clinical development, a work that has resulted in the registration of several PARP inhibitors in breast (olaparib and talazoparib) and ovarian cancer (olaparib, niraparib and rucaparib, either alone or following platinum chemotherapy as maintenance therapy). Over the past 10 years, our knowledge on the mechanism of action of PARP inhibitor as well as how tumours become resistant has been extended, and we summarise this work here. We also discuss opportunities for expanding the precision medicine approach with PARP inhibitors, identifying a wider population who could benefit from this drug class. This includes developing and validating better predictive biomarkers for patient stratification, mainly based on homologous recombination defects beyond BRCA1/BRCA2 mutations, identifying DNA repair deficient tumours in other cancer types such as prostate or pancreatic cancer, or by designing combination therapies with PARP inhibitors.
Studying the Manifold Structure of Alzheimer's Disease: A Deep Learning Approach Using Convolutional Autoencoders

Many classical machine learning techniques have been used to explore Alzheimer's disease (AD), evolving from image decomposition techniques such as principal component analysis toward higher complexity, non-linear decomposition algorithms. With the arrival of the deep learning paradigm, it has become possible to extract high-level abstract features directly from MRI images that internally describe the distribution of data in low-dimensional manifolds. In this work, we try a new exploratory data analysis of AD based on deep convolutional autoencoders. We aim at finding links between cognitive symptoms and the underlying neurodegeneration process by fusing the information of neuropsychological test outcomes, diagnoses, and other clinical data with the imaging features extracted solely via a data-driven decomposition of MRI. The distribution of the extracted features in different combinations is then analyzed and visualized using regression and classification analysis, and the influence of each coordinate of the autoencoder manifold over the brain is estimated. The imaging-derived markers could then predict clinical variables with correlations above 0.6 in the case of neuropsychological evaluation variables such as the MMSE or the ADAS11 scores, achieving a classification accuracy over 80% for the diagnosis of AD.
Relationship between circulating concentration of Ang II, ADM and ADT and left ventricular hypertrophy in hypertension.

BACKGROUND Left ventricular hypertrophy (LVH) is the most common structural damage in hypertensive complication and is an independent risk factor for assessing cardiovascular events. The aim of this study was explore the relationship between plasma concentration of angiotensin II (Ang II), Adrenomedulin (ADM) and adrenotensin (ADT) in patients with hypertension and LVH. METHODS We enrolled 310 hypertensive patients from the department of cardiology of Tianjin Union Medical Center as the hypertension group and 39 healthy subjects as control group. Further grouping according to the LVMI (male LVMI≥115 g/m2, female LVMI≥95 g/m2) values for determining LVH in the 2013 ESC Hypertension Management Guidelines. Plasma levels of Ang II, ADM and ADT were measured using ELISA assay. RESULTS The levels of plasma Ang II and ADM in essential hypertension (EH) were significantly higher than control group, and the essential hypertension combined left ventricular hypertrophy (EHCLVH) group was higher than essential hypertension not with left ventricular hypertrophy (EHNLVH) group (P<0.05). Correlation analyze showed that left ventricular mass index (LVMI) was positively related to Ang II and ADM, and negatively related to ADT. Logistic regression analyze indicated that LVH are strongly linked with systolic blood pressure (SBP), Ang II, ADM and ADT. ROC curve showed ADM and ADT have similar value in distinguish LVH. CONCLUSION Plasma levels of Ang II, ADM and ADT might act as indicator to identify hypertensive LVH.
Effect of alcohol on the sense of agency in healthy humans

Even at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N‐methyl‐D‐aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo “vehicle,” or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.
Is there section deformation resulting in differential change of nuclear numerical densities along the z axis of thick methacrylate or paraffin sections?

The optical disector, a three‐dimensional counting frame or probe in stereology, is often positioned in the middle (depth) of a thick section for unbiased nuclear counting. Using 30–40 μm thick methacrylate or paraffin sections for nuclear counting of neurons with the optical disector, however, some studies showed markedly higher nuclear densities at 10% of the section thickness near the top or bottom surface of the section, suggestive of deformation of section along its z axis and thus affecting the number estimation. To verify the findings, this study obtained two sets of 12–14 methacrylate sections (average thicknesses 21.7 and 29.4 μm) and two sets of 12 paraffin sections (average thicknesses 13.8 and 29.2 μm) from mature rat testes. Each section was used to count round spermatid nuclei in the seminiferous epithelium densely packed with the cells, using 3–4 consecutive disectors placed vertically (along the z axis of the section) from the top surface of the section, through the whole section thickness (two sets of methacrylate and paraffin sections) or in 80–83% of the thickness (other sections). The results demonstrated that, overall, there were no considerable nonuniform changes of the nuclear densities along the z axis of the sections.