Miracle-dz/UniFAR-FTUs huggingface dataset:
Noninvasive evaluation of pulmonary artery pressure during exercise: the importance of right atrial hypertension

Introduction Identification of elevated pulmonary artery pressures during exercise has important diagnostic, prognostic and therapeutic implications. Stress echocardiography is frequently used to estimate pulmonary artery pressures during exercise testing, but data supporting this practice are limited. This study examined the accuracy of Doppler echocardiography for the estimation of pulmonary artery pressures at rest and during exercise. Methods Simultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP. Results Estimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15–16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p<0.0001; bias −1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p<0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (−14–25 mmHg). Conclusions The RV–RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures. This study shows that the right atrial component of the estimated pulmonary artery pressure equation is often overlooked, but quite important, and failure to account for this leads to substantial underestimation of the severity of exercise-induced PH http://bit.ly/32xgKTD
Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4

The two component regulatory system PhoP/PhoQ is essential for Salmonellae virulence for mice1 and humans.2 PhoQ is a sensor histidine kinase that responds to environmental conditions such as within mammalian tissues, macrophage phagosomes, magnesium-limited growth medium, and exposure to antimicrobial peptides (reviewed by Scherer and Miller3 and Bader et al.,4 and summarized in Figure 1). In response to specific environmental signals, PhoQ phosphorylates the transcriptional effecter protein PhoP, leading to the activation or repression of over 40 different genes (reviewed by Scherer and Miller3). The genes regulated by PhoP/PhoQ are named PhoP/PhoQ-activated gene, pag, or PhoP/PhoQ-repressed gene, prg (Fig. 1). 3 PhoP/PhoQ-regulated modification of lipid A, a component of lipopolysaccharide (LPS) that is also known as endotoxin, is one of the best-characterized components of the Salmonellae outer membrane.5 The structure of lipid A is relatively conserved among different enteric bacteria,6 and the conserved lipid A structure of Escherichia coli and Salmonella typhimurium is shown in Figure 2. S. typhymurium synthesizes lipid A modification enzymes, including PagL7 and PagP8,9 in response to environmental conditions through activation of PhoP/PhoQ (Fig. 1). pagP and pagL encode a lipid A palmitoyltransferase and 3-O-deacylase, respectively, both of which are localized in the bacterial outer membrane.7,9 Previously, when a heterogeneous mixtures of modified LPS species from PhoP-constitutive and PhoPnull Salmonellae strains were analyzed for pro-inflammatory responses, PhoP-dependent reduction in LPS-induced TNF-α production was observed in adherent monocytes.5 This suggested that bacteria remodel their cell surface upon infection of a host, i.e. specific LPS modification that may benefit the bacteria by reducing host innate immune
Temporal tuning of repetition suppression across the visual cortex

The visual system adapts to its recent history. A phenomenon related to this is repetition suppression (RS) - a reduction in neural responses to repeated compared to non-repeated visual input. An intriguing hypothesis is that the timescale over which RS occurs across the visual hierarchy is tuned to the temporal statistics of visual input features, which change rapidly in low-level areas but are more stable in higher-level areas. Here, we tested this hypothesis by studying the influence of the temporal lag between successive visual stimuli on RS throughout the visual system using fMRI. Twelve human volunteers engaged in four fMRI sessions in which we characterized the BOLD response to pairs of repeated and non-repeated natural images with inter-stimulus intervals (ISI) ranging from 50 to 1000 milliseconds to quantify the temporal tuning of RS along the posterior-anterior axis of the visual system. As expected, RS was maximal for short ISIs and decayed with increasing ISI. Furthermore, the overall magnitude of RS gradually increased from posterior to anterior visual areas. Crucially, however, and against our hypothesis, RS decayed at a similar rate in early and late visual areas. This finding challenges the prevailing view that the timescale of RS increases along the posterior-anterior axis of the visual system and suggests that RS is not tuned to temporal input regularities.
A tumor suppressor DLC1: The functions and signal pathways

Deleted in liver cancer‐1 (DLC1), a potential tumor suppressor, acts as a GTPase‐activating protein for Rho family members. In many human cancers, the DLC1 expression is frequently downregulated or inactivated, which allows cancer cells to proliferate and disseminate. In this review, we describe the characteristics and other members of the DLC1 family and delineate the signal pathways DLC1 involved in regulating cancer cell growth, colony formation, apoptosis, senescence, autophagy, migration and invasion. In addition, we explore the clinical data of DLC1 and the mechanisms that natural products upregulate the DLC1 expression to inhibit cancer. Despite these insights, many important unanswered questions remain about the exact mechanisms of DLC1‐mediated cancer suppression.
Cohort profile: the Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort, a prospective preterm birth cohort in New York City

Purpose The Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) longitudinal preterm birth cohort studies the impact of the NICU exposome on early-life development. NICU-HEALTH collects multiple biospecimens, complex observational and survey data and comprehensive multisystem outcome assessments to allow measurement of the impact of modifiable environmental exposures during the preterm period on neurodevelopmental, pulmonary and growth outcomes. Participants Moderately preterm infants without genetic or congenital anomalies and their mothers are recruited from an urban academic medical centre level IV NICU in New York City, New York, USA. Recruitment began in 2011 and continues through multiple enrolment phases to the present with goal enrolment of 400 infants. Follow-up includes daily data collection throughout the NICU stay and six follow-up visits in the first 2 years. Study retention is 77% to date, with the oldest patients turning age 8 in 2019. Findings to date NICU-HEALTH has already contributed significantly to our understanding of phthalate exposure in the NICU. Phase I produced the first evidence of the clinical impact of phthalate exposure in the NICU population. Further study identified specific sources of exposure to clinically relevant phthalate mixtures in the NICU. Future plans Follow-up from age 3 to 12 is co-ordinated through integration with the Environmental Influences on Child Health Outcomes (ECHO) programme. The NICU-HEALTH cohort will generate a wealth of biomarker, clinical and outcome data from which future studies of the impact of early-life chemical and non-chemical environmental exposures can benefit. Findings from study of this cohort and other collaborating environmental health cohorts will likely translate into improvements in the hospital environment for infant development. Trial registration numbers This observational cohort is registered with ClinicalTrials.gov (NCT01420029 and NCT01963065).
User Engagement and Attrition in an App-Based Physical Activity Intervention: Secondary Analysis of a Randomized Controlled Trial

Background The success of a mobile phone app in changing health behavior is thought to be contingent on engagement, commonly operationalized as frequency of use. Objective This subgroup analysis of the 2 intervention arms from a 3-group randomized controlled trial aimed to examine user engagement with a 100-day physical activity intervention delivered via an app. Rates of engagement, associations between user characteristics and engagement, and whether engagement was related to intervention efficacy were examined. Methods Engagement was captured in a real-time log of interactions by users randomized to either a gamified (n=141) or nongamified version of the same app (n=160). Physical activity was assessed via accelerometry and self-report at baseline and 3-month follow-up. Survival analysis was used to assess time to nonuse attrition. Mixed models examined associations between user characteristics and engagement (total app use). Characteristics of super users (top quartile of users) and regular users (lowest 3 quartiles) were compared using t tests and a chi-square analysis. Linear mixed models were used to assess whether being a super user was related to change in physical activity over time. Results Engagement was high. Attrition (30 days of nonuse) occurred in 32% and 39% of the gamified and basic groups, respectively, with no significant between-group differences in time to attrition (P=.17). Users with a body mass index (BMI) in the healthy range had higher total app use (mean 230.5, 95% CI 190.6-270.5; F2=8.67; P<.001), compared with users whose BMI was overweight or obese (mean 170.6, 95% CI 139.5-201.6; mean 132.9, 95% CI 104.8-161.0). Older users had higher total app use (mean 200.4, 95% CI 171.9-228.9; F1=6.385; P=.01) than younger users (mean 155.6, 95% CI 128.5-182.6). Super users were 4.6 years older (t297=3.6; P<.001) and less likely to have a BMI in the obese range (χ22=15.1; P<.001). At the 3-month follow-up, super users were completing 28.2 (95% CI 9.4-46.9) more minutes of objectively measured physical activity than regular users (F1,272=4.76; P=.03). Conclusions Total app use was high across the 100-day intervention period, and the inclusion of gamified features enhanced engagement. Participants who engaged the most saw significantly greater increases to their objectively measured physical activity over time, supporting the theory that intervention exposure is linked to efficacy. Further research is needed to determine whether these findings are replicated in other app-based interventions, including those experimentally evaluating engagement and those conducted in real-world settings. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12617000113358; https://www.anzctr. org.au/ACTRN12617000113358.aspx
Choroba zwyrodnieniowa stawów - problem wieloaspektowy

Summary Osteoarthritis is a progressive disease causing pain and structural and functional changes in the affected joints. The increasing incidence of the disease is associated with society aging and the obesity epidemic. This progressing chronic disease causes disability and loss of independence. Treatment of this disease is focused on pain relief and includes treatment with non-steroidal anti-inflammatory drugs, diet supplements with glucosamine, chondroitin, and injections of hyaluronic acid into the affected joint. A very important part of treatment is physiotherapy as well as non-pharmacological treatment including patient education, body weight reduction, use of orthopedic equipment facilitating motility and kinesitherapy. The article is a review of the osteoarthritis literature, the disease pathophysiology and the ways of treatment.
Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD.
Pleural small cell carcinoma with massive pleural effusion

Abstract Rationale: Small cell carcinoma (SCC) occurs mostly in the lung, and small cell lung cancer accounts for 13% of newly diagnosed lung cancers. Only 2.5% of SCC occurs in extrapulmonary sites, and SCC of pleural origin is especially very uncommon. Patient concerns: An 85-year-old man presenting with progressive dyspnea for more than 7 days. Diagnoses: Computed tomography scan of the chest showed massive pleural effusion and diffuse nodular thickening of the pleura on the right chest. Sonography-guided needle biopsy of the pleural mass was performed and histologic and immunohistochemical findings revealed SCC. Since no parenchymal lung lesion was observed, the patient was finally diagnosed with SCC of the pleura (SCCP). Interventions: Due to the patient's old age and poor performance status, chemotherapy was not performed and only drainage of pleural effusion was conducted for symptom relief. Outcomes: Dyspnea improved after pleural effusion drainage. The patient was discharged and transferred to a local medical center for hospice care. Lessons: Although primary SCCP is extremely rare, SCCP should also be considered as well as mesothelioma in case of presence of a pleural-based mass with massive pleural effusion.
The Effect of Paraspinal Muscle Degeneration on Distal Pedicle Screw Loosening Following Corrective Surgery for Degenerative Lumbar Scoliosis.

STUDY DESIGN A retrospective study. OBJECTIVE To evaluate the effect of degeneration of paraspinal muscles, including psoas muscles, erector spinae muscles and multifidus muscles on pedicle screw loosening at lower instrumented vertebra (LIV) following corrective surgery for degenerative lumbar scoliosis (DLS). SUMMARY OF BACKGROUND DATA The relation between paraspinal muscles and pedicle screw loosening in DLS patients has not been reported. METHODS 137 DLS patients underwent corrective surgery with at least one-year follow-up were included. The patients were divided into two groups: Group A (68 patients) had 6 or more fused levels and Group B (69 patients) had 4 or 5 fused levels. Muscular parameters, including relative cross-sectional area (rCSA) and muscle-fat index (MFI) were measured on preoperative Magnetic Resonance Imaging. rCSA and MFI were measured for both gross muscle (G) and functional muscle (F) as rGCSA, rFCSA, GMFI and FMFI. Muscle ratio was calculated as rFCSA/rGCSA. Pedicle screw loosening was assessed on spine radiographs or CT at final follow-up. Clinical and radiological screw loosening were classified according to clinical significance. RESULTS LIV screw loosening occurred in 77 patients at final follow-up. In Group A, patients with LIV screw loosening had significantly higher FMFI of psoas muscles and lower rFCSA and rGCSA of erector spinae. Logistic regression revealed that mean rFCSA of erector spinae < 0.71 (OR = 5.0, 95% CI = 1.5-16.4) was an independent risk factor of LIV screw loosening. Mean muscle ratio of erector spinae was significantly lower in patients with clinical screw loosening compared with radiological screw loosening in univariate analysis. In Group B, all muscular parameters showed no significant difference. CONCLUSIONS Degeneration of paraspinal muscles, especially psoas muscles and erector spinae, affected LIV screw loosening in 6 or more level fusion in corrective surgery for DLS, whereas the 4 or 5 level fusion had no this influence. LEVEL OF EVIDENCE 3.
EUROPEAN SCHOOL OF MOLECULAR MEDICINE

5 INTRODUCTION 7 1. Epidermal development 7 2. p63: structure and expression 13 3. BMP Signaling 17 5. Cell Cycle 21 6. microRNA 26 MATERIALS AND METHODS 31 1. Keratinocytes preparation and cell cultures 31 2. Chromatin immunoprecipitation 31 3. Constructs, transfections and reporter assays 32 4. Retroviral infections. 34 5. Analysis of gene expression 34 6. Real-time RT-PCR 35 7. Immunostaining. 38 8. Immunoblotting 39 9. in situ hybridization 39 10. Mice and Skin Explants 40 11. Flow cytometry and BrdU labeling 41 12. miRNA expression analysis 42 RESULTS 43
Temperature‐Invariant Superelastic and Fatigue Resistant Carbon Nanofiber Aerogels

Superelastic and fatigue‐resistant materials that can work over a wide temperature range are highly desired for diverse applications. A morphology‐retained and scalable carbonization method is reported to thermally convert a structural biological material (i.e., bacterial cellulose) into graphitic carbon nanofiber aerogel by engineering the pyrolysis chemistry. The prepared carbon aerogel perfectly inherits the hierarchical structures of bacterial cellulose from macroscopic to microscopic scales, resulting in remarkable thermomechanical properties. In particular, it maintains superelasticity without plastic deformation even after 2 × 106 compressive cycles and exhibits exceptional temperature‐invariant superelasticity and fatigue resistance over a wide temperature range at least from −100 to 500 °C. This aerogel shows unique advantages over polymeric foams, metallic foams, and ceramic foams in terms of thermomechanical stability and fatigue resistance, with the realization of scalable synthesis and the economic advantage of biological materials.
Hypoxia Inducible Factor-1α in Osteochondral Tissue Engineering

Damage to osteochondral (OC) tissues can lead to pain, loss of motility, and progress to osteoarthritis. Tissue engineering approaches offer the possibility of replacing damaged tissues and restoring joint function; however, replicating the spatial and functional heterogeneity of native OC tissue remains a pressing challenge. Chondrocytes in healthy cartilage exist in relatively low-oxygen conditions, while osteoblasts in the underlying bone experience higher oxygen pressures. Such oxygen gradients also exist in the limb bud, where they influence OC tissue development. The cellular response to these spatial variations in oxygen pressure, which is mediated by the hypoxia inducible factor (HIF) pathway, plays a central role in regulating osteo- and chondrogenesis by directing progenitor cell differentiation and promoting and maintaining appropriate extracellular matrix production. Understanding the role of the HIF pathway in OC tissue development may enable new approaches to engineer OC tissue. In this review, we discuss strategies to spatially and temporarily regulate the HIF pathway in progenitor cells to create functional OC tissue for regenerative therapies. Impact statement Strategies to engineer osteochondral (OC) tissue are limited by the complex and varying microenvironmental conditions in native bone and cartilage. Indeed, native cartilage experiences low-oxygen conditions, while the underlying bone is relatively normoxic. The cellular response to these low-oxygen conditions, which is mediated through the hypoxia inducible factor (HIF) pathway, is known to promote and maintain the chondrocyte phenotype. By using tissue engineering scaffolds to spatially and temporally harness the HIF pathway, it may be possible to improve OC tissue engineering strategies for the regeneration of damaged cartilage and its underlying subchondral bone.
Development of a risk score for colorectal cancer in Chinese males: A prospective cohort study

To build a simple predictive model as a guide to stratify average‐risk population for colonoscopy examinations. We collected data from 92 923 males without a prior history of cancer enrolled in the Kailuan Cohort Study of China. Risk factors included in the evaluation of colorectal cancer (CRC) were collected by questionnaire‐based interviews at the baseline. Logistic regression coefficients for incident CRC predictors were converted into risk scores by the absolute value of the smallest coefficient in the model and rounding up to the nearest integer. Receiver operating characteristic (ROC) analysis with the leave‐one‐out cross‐validation method was applied to evaluate model performance. In the 10‐year follow‐up, 353 CRC patients were in the cohort. Age, alcohol consumption, waist circumference, occupational sitting time, and history of diabetes were selected for the scoring system, and the adjusted area under the ROC was 0.66. Population in the highest risk group (16‐19 points) had a 33.12‐fold (95% CI: 13.44‐81.59) higher risk of CRC than those in the lowest risk group. When we defined 13 points as the cut‐off, the sensitivity and specificity of the scoring system for CRC were 67.99% and 62.42%, respectively. A simple scoring system for CRC has been developed to identify men at an increased relative risk of CRC within 10 years using several well‐established risk factors, which allows selection of asymptomatic candidates for priority of CRC screening and saving the health resource in cancer prevention and control.
Novel Flavonoid Glycosides of Quercetin from Leaves and Flowers of Gaiadendron punctatum G.Don. (Violeta de Campo), used by the Saraguro Community in Southern Ecuador, Inhibit α-Glucosidase Enzyme

Gaiadandendron punctatum G.Don. (violeta de campo) is a plant used in traditional medicine by the Saraguro people, an ancient indigenous group that lives in southern Ecuador. From samples collected in the region, six glycoside flavonoids, five with quercetin and one with kaempferol as aglycon, were isolated and characterized from hydroalcoholic extracts of leaves and flowers. Rutin (2) was found in flowers and leaves, nicotiflorin (1) was found in flowers, artabotryside A (3) was found in leaves, and three novel quercetin flavonoid glycosides were isolated, elucidated, and characterized via 1D and 2D NMR experiments (1H, 13C, COSY, DEPT, HMBC, HSQC, TOCSY, NOESY, ROESY), acid hydrolysis–derivatization–GC-MS analysis, HPLC-MS, IR, UV, and optical rotation. The new quercetin flavonoid glycosides were named hecpatrin (4) (isolated from leaves), gaiadendrin (5) (isolated from leaves), and puchikrin (6) (isolated from flowers). The hydroalcoholic extracts of the leaves presented antimicrobial activity against Micrococcus luteus, Staphylococcus aureus, and Enterococcus faecalis and the hydroalcoholic extract of the flowers was active against Micrococcus luteus. However, glycoside flavonoids presented scarce antimicrobial activity against bacteria. Hydroalcoholic extracts from leaves and flowers and their secondary metabolites showed inhibition against the α-glucosidase enzyme at different concentrations. Rutin, gaiadendrin, and nicotiflorin showed competitive α-glucosidase inhibition, while hecpatrin presented non-competitive inhibition.