Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalent osteoporotic vertebral fractures more likely involve the upper endplate than the lower endplate and even more so in males.

Background While the importance of identifying osteoporotic vertebral endplate fracture (EPF) is being recognized; the pathophysiological understanding of EPF till now remain insufficient. In this population-based cross-sectional radiograph study, we aim to investigate the anatomic location characteristics of osteoporotic EPF. Methods This study analyzed the anatomical location of osteoporotic EPFs in elderly Chinese population (age ≥65 years). The T4-L4 radiographs of 1,954 elderly Chinese men (mean: 72.3 years) and 1,953 elderly Chinese women (mean: 72.5 years) were evaluated to identify EPF, and vertebral bodies were graded according to Genant's vertebral deformity criteria. Results Of the 101,582 endplates analyzed, there were 505 EPFs (males: 27.7%; females: 72.3%). Excluding those with both upper endplate and lower endplate involvements, the ratio of upper EPF to lower EPF was 9.63 for males and 4.3 for females (P<0.05). Thoracolumbar junction, particularly L1 (26.4% for males and 24.1% for females) and followed by T12 (20.7% for males and 19.7% for females), had highest prevalence of EPF. With an endplate divided into 5 segments of equal length in the anteroposterior direction and grade 0.5 & 1, grade 2 vertebral deformities analyzed, fractures occurred mostly at the middle segment (70.1% for upper endplates in males and 78.6% for upper endplates in females), followed by second anterior segment (20.9% for upper endplates in males and 14.4% for upper endplates in females). The most anterior and most posterior segments were not primarily involved in EPF. Conclusions Osteoporotic EPFs more likely involve the upper endplate rather than lower endplate, with a trend for this effect to be greater in men than in women. These characteristics may help radiographic differential diagnosis for osteoporotic EPF.
Investigating sensitivity coefficients characterizing the response of a model of tau protein transport in an axon to model parameters

Abstract Evaluating the sensitivity of biological models to various model parameters is a critical step towards advancing our understanding of biological systems. In this paper, we investigated sensitivity coefficients for a model simulating transport of tau protein along the axon. This is an important problem due to the relevance of tau transport and agglomeration to Alzheimer’s disease and other tauopathies, such as some forms of parkinsonism. The sensitivity coefficients that we obtained characterize how strongly three observables (the tau concentration, average tau velocity, and the percentage of tau bound to microtubules) depend on model parameters. The fact that the observables strongly depend on a parameter characterizing tau transition from the retrograde to the anterograde kinetic states suggests the importance of motor-driven transport of tau. The observables are sensitive to kinetic constants characterizing tau concentration in the free (cytosolic) state only at small distances from the soma. Cytosolic tau can only be transported by diffusion, suggesting that diffusion-driven transport of tau only plays a role in the proximal axon. Our analysis also shows the location in the axon in which an observable has the greatest sensitivity to a certain parameter. For most parameters, this location is in the proximal axon. This could be useful for designing an experiment aimed at determining the value of this parameter. We also analyzed sensitivity of the average tau velocity, the total tau concentration, and the percentage of microtubule-bound tau to cytosolic diffusivity of tau and diffusivity of bound tau along the MT lattice. The model predicts that at small distances from the soma the effect of these two diffusion processes is comparable.
Animal prion diseases: the risks to human health

Transmissible spongiform encephalopathies (TSEs) or prion diseases of animals notably include scrapie in small ruminants, chronic wasting disease (CWD) in cervids and classical bovine spongiform encephalopathy (C‐BSE). As the transmission barrier phenomenon naturally limits the propagation of prions from one species to another, and the lack of epidemiological evidence for an association with human prion diseases, the zoonotic potential of these diseases was for a long time considered negligible. However, in 1996, C‐BSE was recognized as the cause of a new human prion disease, variant Creutzfeldt‐Jakob disease (vCJD), which triggered an unprecedented public health crisis in Europe. Large‐scale epidemio‐surveillance programs for scrapie and C‐BSE that were implemented in the EU after the BSE crisis revealed that the distribution and prevalence of prion diseases in the ruminant population had previously been underestimated. They also led to the recognition of new forms of TSEs (named atypical) in cattle and small ruminants and to the recent identification of CWD in Europe. At this stage, the characterization of the strain diversity and zoonotic abilities associated with animal prion diseases remains largely incomplete. However, transmission experiments in nonhuman primates and transgenic mice expressing human PrP clearly indicate that classical scrapie, and certain forms of atypical BSE (L‐BSE) or CWD may have the potential to infect humans. The remaining uncertainties about the origins and relationships between animal prion diseases emphasize the importance of the measures implemented to limit human exposure to these potentially zoonotic agents, and of continued surveillance for both animal and human prion diseases.
Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis: An Observational Cohort Study

Rationale: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. Objective: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. Methods and Results: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (&bgr;=0.10; P=0.020) and oxHDL (&bgr;=−0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03). Conclusions: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.
Burden of Streptococcus pneumoniae sepsis in children after introduction of pneumococcal conjugate vaccines - a prospective population-based cohort study.

Background Population-based studies assessing the impact of pneumococcal conjugate vaccines (PCV) on burden of pneumococcal sepsis in children are lacking. We aimed to assess this burden following introduction of PCV-13 in a nationwide cohort study. Methods The Swiss Pediatric Sepsis Study (09/2011-12/2015) prospectively recruited children <17 years of age with blood culture-proven sepsis due to Streptococcus pneumoniae, meeting criteria for systemic inflammatory response syndrome. Infection with vaccine serotype in children up to date with PCV immunization was defined as vaccine failure. Main outcomes were admission to pediatric intensive care unit (PICU) and length of hospital stay (LOS). Results Children with pneumococcal sepsis (n=117) accounted for a crude incidence of 2.0 per 100,000 children (95% CI 1.7-2.4) and 25% of community-acquired sepsis episodes. Case fatality rate was 8%. 42 (36%) patients required PICU admission. Children with meningitis (29; 25%) were more often infected by serotypes not included in PCV (69% vs 31%; p<0.001). 16 (26%) of 62 children up to date with PCV immunization presented with vaccine failure, including 11 infected with serotype 3. In multivariable analyses, children with meningitis (OR 6.8; 95% C.I 2.4-19.3; p<0.001), or infected with serotype 3 (OR 2.8; 95% C.I 1.1- 7.3; p=0.04) were more often admitted to PICU. Children infected with serotype 3 had longer LOS ( coefficient 0.2, 95% CI 0.1-1.1; p=0.01). Conclusions The incidence of pneumococcal sepsis in children shortly after introduction of PCV-13 remained substantial. Meningitis mostly due to non-vaccine serotypes and disease caused by serotype 3 represented significant predictors of severity.
Validation of the Children's Intrinsic Needs Satisfaction Scale among Canadian youth: psychometric properties, criterion-related validity and multitrait multimethod confirmatory factor analysis.

INTRODUCTION Based on self-determination theory, the Children's Intrinsic Needs Satisfaction Scale (CINSS) measures autonomy, competence and relatedness at school, home and with peers. The factor structure and criterion-related validity of the CINSS in the Canadian youth population are tested using data from the Canadian Student Tobacco, Alcohol and Drugs Survey (CSTADS). METHODS Data from the 2014/2015 CSTADS were analyzed for evidence of convergent and discriminant validity and for method variance. A multitrait multimethod (MTMM) confirmatory factor analysis (CFA) was conducted to account for the conceptual structure of the measure. Criterion-related validity was demonstrated through correlations between related constructs, prosocial behaviours and behavioural problems, and the CINSS subscale scores. Mean differences on CINSS subscale scores between those who reported and did not report being bullied or bullying others were also examined. RESULTS Correlation analyses demonstrated that, in general, correlations were higher between concept/context item pairs and lowest between items measuring different concepts and contexts. Cronbach's alpha for concept and context subscales were high: α = 0.77 for autonomy, α = 0.85 for competence and α = 0.79 for relatedness. A MTMM CFA demonstrated that the model fit the data well, with no modifications. Criterion-related validity was demonstrated through correlations between CINSS subscales and related concepts or mean differences on CINSS subscales between groups. CONCLUSION The CINSS demonstrates good internal consistency, factorial validity and criterion-related validity in this sample of Canadian students. The measurement of positive mental health among Canadian youth is central to surveillance efforts which will help inform mental health promotion activities across Canada.
Influence of the level of sacrectomy on survival in patients with locally advanced and recurrent rectal cancer

Exenterative surgery for locally advanced rectal cancer may involve partial sacrectomy to achieve complete resection. High sacrectomy is technically challenging, and can be associated with high morbidity and mortality rates. The aim of this study was to determine the influence of the level of sacrectomy on the survival of patients with locally advanced rectal cancer.
Oxygen and lack of oxygen in fetal and placental development, feto–placental coupling, and congenital heart defects

Low oxygen concentration (hypoxia) is part of normal embryonic development, yet the situation is complex. Oxygen (O2) is a janus gas with low levels signaling through hypoxia‐inducible transcription factor (HIF) that are required for development of fetal and placental vasculature and fetal red blood cells. This results in coupling of fetus and mother around midgestation as a functional feto‐placental unit (FPU) for O2 transport, which is required for continued growth and development of the fetus. Defects in these processes may leave the developing fetus vulnerable to O2 deprivation or other stressors during this critical midgestational transition when common septal and conotruncal heart defects (CHDs) are likely to arise. Recent human epidemiological and case–control studies support an association between placental dysfunction, manifest as early onset pre‐eclampsia (PE) and increased serum bio‐markers, and CHD. Animal studies support this association, in particular those using gene inactivation in the mouse. Sophisticated methods for gene inactivation, cell fate mapping, and a quantitative bio‐reporter of O2 concentration support the premise that hypoxic stress at critical stages of development leads to CHD. The secondary heart field contributing to the cardiac outlet is a key target, with activation of the un‐folded protein response and abrogation of FGF signaling or precocious activation of a cardiomyocyte transcriptional program for differentiation, suggested as mechanisms. These studies provide a strong foundation for further study of feto–placental coupling and hypoxic stress in the genesis of human CHD.
Impact of tumor‐associated macrophages and BRAFV600E mutation on clinical outcomes in patients with various thyroid cancers

Tumor‐associated macrophages (TAMs) play a role in thyroid cancer tumor progression and metastasis. This study aimed to investigate the association of TAM density and cluster of differentiation 68 (CD68) expression with thyroid tumors as a prognostic marker and the relationship of these factors with BRAFV600E mutations.
The Mechanics of Breathing during Swimming.

The thorax undergoes unique conditions while swimming. Hydrostatic pressure from water immersion places an external load on the thorax and increases airway resistance, and the horizontal body position results in central venous engorgement and an associated reduction in lung compliance. The aforementioned factors likely increase the work of breathing (Wb); however, this hypothesis remains untested. PURPOSE This study aimed to compare Wb during freestyle swimming relative to cycling and to characterize the differences in the cardiorespiratory responses to swimming relative to cycling in the same individuals. METHODS Eight collegiate swimmers (four men and four women, age = 22 ± 2 yr) performed an incremental swim test while tethered to a resistance apparatus. On a separate day, subjects performed an incremental cycle test. During swimming and cycling, metabolic and ventilatory parameters were measured using a customized metabolic cart, and inspired Wb was quantified using an esophageal balloon catheter. RESULTS Swimming and cycling elicited statistically similar levels of peak oxygen uptake (3.87 ± 0.92 vs 4.20 ± 0.83 L·min, P = 0.143). However, peak minute ventilation (V˙E) (118 ± 3 vs 154 ± 25 L·min) and heart rate (164 ± 19 vs 183 ± 8 bpm) were significantly lower during swimming relative to cycling (both P < 0.05). Inspired Wb was higher at a V˙E of 50 L·min (+27 ± 16 J·min), 75 L·min (+56 ± 23 J·min), and 100 L·min (+53 ± 22 J·min) during swimming compared with cycling (all P < 0.05). Periods of interbreath apnea were observed while swimming (duration = 0.13-2.07 s). CONCLUSION We interpret our findings to mean that the horizontal body position and hydrostatic pressure on the chest wall requires swimmers to generate greater inspiratory pressures to sustain adequate V˙E during exercise.
Dynamic Control of Light Direction Enabled by Stimuli‐Responsive Liquid Crystal Gratings

The ability to control light direction with tailored precision via facile means is long‐desired in science and industry. With the advances in optics, a periodic structure called diffraction grating gains prominence and renders a more flexible control over light propagation when compared to prisms. Today, diffraction gratings are common components in wavelength division multiplexing devices, monochromators, lasers, spectrometers, media storage, beam steering, and many other applications. Next‐generation optical devices, however, demand nonmechanical, full and remote control, besides generating higher than 1D diffraction patterns with as few optical elements as possible. Liquid crystals (LCs) are great candidates for light control since they can form various patterns under different stimuli, including periodic structures capable of behaving as diffraction gratings. The characteristics of such gratings depend on several physical properties of the LCs such as film thickness, periodicity, and molecular orientation, all resulting from the internal constraints of the sample, and all of these are easily controllable. In this review, the authors summarize the research and development on stimuli‐controllable diffraction gratings and beam steering using LCs as the active optical materials. Dynamic gratings fabricated by applying external field forces or surface treatments and made of chiral and nonchiral LCs with and without polymer networks are described. LC gratings capable of switching under external stimuli such as light, electric and magnetic fields, heat, and chemical composition are discussed. The focus is on the materials, designs, applications, and future prospects of diffraction gratings using LC materials as active layers.
Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials

Background: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. Methods: Data from 9 global clinical trials (2009–2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre–diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient- and trial-level variables associated with undetermined cause of death were identified using a logistic model. Results: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre–diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. Conclusions: In 9 cardiometabolic clinical trials with long-term follow-up, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.
Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10−8; and LINC00539/ZDHHC20, p = 5.82 × 10−9. Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10−25; p[SSBI] = 5.23 × 10−14 for hypertension), smoking (p[BI] = 4.4 × 10−10; p[SSBI] = 1.2 × 10−4), diabetes (p[BI] = 1.7 × 10−8; p[SSBI] = 2.8 × 10−3), previous cardiovascular disease (p[BI] = 1.0 × 10−18; p[SSBI] = 2.3 × 10−7), stroke (p[BI] = 3.9 × 10−69; p[SSBI] = 3.2 × 10−24), and MRI-defined white matter hyperintensity burden (p[BI] = 1.43 × 10−157; p[SSBI] = 3.16 × 10−106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.