Miracle-dz/UniFAR-FTUs huggingface dataset:
The peripheral blood neutrophil-to-lymphocyte ratio is a prognostic predictor for survival of EGFR-mutant nonsmall cell lung cancer patients treated with EGFR-TKIs

Abstract Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS) of EGFR-mutant NSCLC patients treated with EGFR-TKIs. The receiver operating characteristic analysis indicated that the lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) cut-off values were 3.37 and 2.90, respectively. The univariate analysis showed that a high LMR (>3.37) and low NLR (⩽2.90) were significantly correlated with long-term PFS and OS (LMR, P = .007; NLR, P < .001). The multivariate Cox regression analysis revealed that only low NLR was an independent prognostic factor for long-term PFS and OS (PFS, HR = 0.573, 95% CI: 0.340–0.964, P = .036; OS, HR = 0.491, 95% CI: 0.262–0.920, P = .026). The data show that a low NLR was a good prognostic factor in EGFR-mutant NSCLC patients receiving EGFR-TKIs treatment. Moreover, the NLR measurement has better prognostic value than LMR.
Effect of improved medication adherence on health care costs in osteoporosis patients

Abstract Osteoporosis is a chronic disease that requires continuous health care spending for pharmacotherapy and examinations. Osteoporotic fractures are a major economic burden. However, little is known about the economic effects of osteoporosis and osteoporotic fractures in Korea. The purpose of this study was to determine the predictors of osteoporosis-related health care costs and to evaluate the economic effects of fracture prevention through medication adherence among osteoporosis patients. Using the Korea National Health Insurance Claims Database (KNHICD), we identified osteoporosis patients aged 50 years and older from 2011 to 2012. Annual health care costs of osteoporosis were analyzed from the insurer's perspective and compared between patients with fractures and those without fractures. Adherents were defined as patients with a medication possession ratio of ≥80%. A generalized linear model (GLM) was used to estimate the predictors of osteoporosis-related health care costs. The major predictors of osteoporosis-related health care costs were age, medication adherence, and the occurrence of fractures (P < .001). The proportion of fractures among non-adherents was approximately 1.1 times the proportion among adherents. Health care costs per patient with fractures were 3.8 times the costs per patient without fractures. Patients with fractures had higher health care costs due to hospitalization and outpatient costs but lower pharmacy costs than non-adherents. We estimated that about $5 million of health insurance expenses could be saved annually if all non-adherents became adherents. Improved osteoporosis medication adherence can reduce osteoporosis-related health care costs by preventing fractures. Persistent pharmacotherapy for osteoporosis is necessary to prevent osteoporotic fractures and to reduce osteoporosis-related health care costs.
Psychosocial Correlates of Vaginismus Diagnosis: A Case-Control Study

Abstract The objective of this case-control study was to identify psychosocial factors associated with vaginismus. One hundred twenty women were recruited and interviewed at the Institute of Human Sexuality, 40 with lifelong vaginismus, and 80 controls without vaginismus. Participants were matched for age, education, and date of admission. Women afraid of losing control during intercourse had 29.6 times greater likelihood of developing vaginismus (p < 0.01), as well as those afraid of suffering pain (p < 0.001) or being physically damaged (tearing) (p < 0.01). There is evidence that women have higher likelihood of vaginismus if they present fears of pain, injuries, bleeding, fear of losing control, and having a panic attack if they engage in sex with penetration.
Left and right ventricular strain in the course of acute myocarditis: a cardiovascular magnetic resonance study

Abstract Purpose To investigate the degree of impairment in left (LV) and right ventricular (RV) myocardial strain parameters over the course of acute myocarditis and to evaluate its value for the prediction of functional recovery upon follow-up. Materials and Methods 69 patients with acute myocarditis underwent cardiac magnetic resonance imaging during the acute stage (baseline) and after a mean 92.5 ± 50.4 days follow-up. Standard “Lake Louise” criteria (T2 signal intensity ratio, early gadolinium enhancement ratio and late gadolinium enhancement) and feature tracking derived LV and RV strain parameters were assessed. Logistic regression analysis was used to find predictors of functional recovery upon follow-up. Results All inflammatory parameters showed a considerable decrease over the course of the disease (P < 0.001 for all parameters). LV and RV function significantly improved on follow-up CMR (LV ejection fraction: 53.5 ± 12.7 % vs. 61.3 ± 9.5 %; P < 0.001, RV ejection fraction: 54.1 ± 10.0 % vs. 59.4 ± 6.3 %; P < 0.001). LV and RV myocardial strain (longitudinal, circumferential and radial strain) significantly improved from baseline to follow-up (P < 0.05 for all parameters). On multivariate analysis, LV global peak systolic longitudinal strain (OR: 0.303; P = 0.007) was the only independent predictor of functional recovery upon follow-up. Conclusion Alterations in LV and RV functional strain parameters occur frequently during the acute stage of myocarditis. During the course of the disease, a significant improvement in LV and RV strain parameters can be observed. It further appears that initial LV longitudinal strain may serve as a new parameter for the prediction of functional recovery upon follow-up. Key Points Myocardial strain parameters significantly improve during the course of acute myocarditis. RV dysfunction can frequently be observed during the acute stage of myocarditis. LV longitudinal strain can independently predict functional recovery upon follow-up. Citation Format Luetkens JA, Petry P, Kuetting D et al. Left and right ventricular strain in the course of acute myocarditis: a cardiovascular magnetic resonance study. Fortschr Röntgenstr 2018; 190: 722 – 732
Effect of Serial Infusions of CER-001, a Pre-&bgr; High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial: A Randomized Clinical Trial

Importance CER-001 is a negatively charged, engineered pre-&bgr; high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography. Objective To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients. Design, Setting, and Participants A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016. Interventions Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins. Main Outcomes and Measures The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Results Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (−0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups. Conclusions and Relevance Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden. Trial Registration ClinicalTrials.gov Identifier: NCT2484378
Why Do Men Report More Opposite-Sex Sexual Partners Than Women? Analysis of the Gender Discrepancy in a British National Probability Survey

In a closed population and defined time period, the mean number of opposite-sex partners reported by men and women should be equal. However, in all surveys, men report more partners. This inconsistency is pivotal to debate about the reliability of self-reported sexual behavior. We used data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey of the British population, to investigate the extent to which survey sampling, accounting strategies (e.g., estimating versus counting), and (mis)reporting due to social norms might explain the inconsistency. Men reported a mean of 14.14 lifetime partners; women reported 7.12. The gender gap of 7.02 reduced to 5.47 after capping the lifetime partner number at the 99th percentile. In addition, adjusting for counting versus estimation reduced the gender gap to 3.24, and further adjusting for sexual attitudes narrowed it to 2.63. Together, these may account for almost two-thirds of the gender disparity. Sampling explanations (e.g., non-U.K.-resident partners included in counts; sex workers underrepresented) had modest effects. The findings underscore the need for survey methods that facilitate candid reporting and suggest that approaches to encourage counting rather than estimating may be helpful. This study is novel in interrogating a range of potential explanations within the same nationally representative data set.
Body fatness at a young age and risks of eight types of cancer: systematic review and meta‐analysis of observational studies

The associations between body fatness at a young age (childhood, adolescence and young adulthood; age ≤ 30 years) and diffuse large B‐cell lymphoma (DLBCL), oesophageal adenocarcinoma, gastric cardia cancer, hepatocellular carcinoma, multiple myeloma, pancreatic cancer, renal cell cancer and thyroid cancer remain inconclusive. We performed a comprehensive systematic literature review and meta‐analysis of observational studies to clarify the associations between body fatness at a young age and the risks of these cancers. PubMed and Web of Science databases were searched for relevant observational studies. Fifty‐six articles yielded data on 27,559 cancer cases, including 3,170 DLBCL, 1,491 oesophageal adenocarcinoma, 1,103 gastric cardia cancer, 1,067 hepatocellular carcinoma, 3,090 multiple myeloma, 7,220 pancreatic cancer, 6,212 renal cell cancer and 4,206 thyroid cancer cases. Each 5 kg m−2 increase in body mass index at a young age was positively associated with DLBCL (relative risk [RR] 1.21, 95% confidence interval [CI] 1.09, 1.35), oesophageal adenocarcinoma (RR 1.88, 95% CI 1.37, 2.57), gastric cardia cancer (RR 1.59, 95% CI 1.15, 2.21), hepatocellular carcinoma (RR 1.31, 95% CI 1.13, 1.51), multiple myeloma (RR 1.23, 95% CI 1.15, 1.30), pancreatic cancer (RR 1.17, 95% CI 1.11, 1.24), renal cell cancer (RR 1.22, 95% CI 1.16, 1.28) and thyroid cancer (RR 1.12, 95% CI 1.07, 1.17). In summary, higher body fatness at a young age increases the risks of developing various types of cancer later in life. Prevention of overweight and obesity in children, adolescents and young adults should therefore be emphasized to reverse the obesity epidemic and thereby avoid further increases in the burden of cancer attributed to excess body fatness.
Structural studies reveal the molecular mechanism of PETase

Poly(ethylene terephthalate) (PET) is a class of plastic material widely used in modern society, but large amounts of PET waste cause severe environmental problems. Obtained from a PET‐consuming bacterium Ideonella sakaiensis, the enzyme PETase exhibits superb hydrolytic activity and substrate preference toward PET. Here, we summarize some recent advances in the crystallographic analysis of PETase. These reports uncover structural features of PETase that are involved in its catalytic activity. In comparison to homologous enzymes, PETase contains an additional disulfide bond as well as an extended β8‐α6 loop. More importantly, the crystal structures of PETase in complex with substrate and product analogs provide critical information for understanding the mechanism of action of PETase. In particular, the wobbling conformation of W156 is closely related to the binding of substrate and product. These new findings are of great importance for further in‐depth research and engineering development of PETase, and should advance the implementation of plastic biodegradation strategy.
A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice

Although cathelicidins in mammals have been well characterized, little is known about the function of cathelicidin in amphibians. In the present study, a novel 24-residue peptide (cathelicidin-NV, ARGKKECKDDRCRLLMKRGSFSYV) belonging to the cathelicidin family was identified from the skin of the plateau frog Nanorana ventripunctata. Cathelicidin-NV showed strong wound healing-promoting activity in a murine model with a full-thickness dermal wound. It directly enhanced the proliferation of keratinocyte cells, resulting in accelerated re-epithelialization of the wound site. Cathelicidin-NV also promoted the proliferation of fibroblasts, the differentiation of fibroblasts to myofibroblasts and collagen production in fibroblasts, which are implicated in wound contraction and repair processes. Furthermore, cathelicidin-NV promoted the release of monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor and transforming growth factor-β1 in vivo and in vitro, which are essential in the wound-healing processes such as migration, proliferation and differentiation. The MAPK (ERK, JNK and p38) signaling pathways were involved in the wound healing-promoting effect. Additionally, unlike other cathelicidins, cathelicidin-NV did not have any direct effect on microbes and showed no cytotoxicity and hemolytic activity toward mammalian cells at concentrations up to 200 µg/ml. This current study may facilitate the understanding of the cellular and molecular events that underlie quick wound healing in N. ventripunctata. In addition, the combination of these properties makes cathelicidin-NV an excellent candidate for skin wound therapeutics.
Both stiff and compliant: morphological and biomechanical adaptations of stick insect antennae for tactile exploration

Active tactile exploration behaviour is constrained to a large extent by the morphological and biomechanical properties of the animal's somatosensory system. In the model organism Carausius morosus, the main tactile sensory organs are long, thin, seemingly delicate, but very robust antennae. Previous studies have shown that these antennae are compliant under contact, yet stiff enough to maintain a straight shape during active exploration. Overcritical damping of the flagellum, on the other hand, allows for a rapid return to the straight shape after release of contact. Which roles do the morphological and biomechanical adaptations of the flagellum play in determining these special mechanical properties? To investigate this question, we used a combination of biomechanical experiments and numerical modelling. A set of four finite-element (FE) model variants was derived to investigate the effect of the distinct geometrical and material properties of the flagellum on its static (bending) and dynamic (damping) characteristics. The results of our numerical simulations show that the tapered shape of the flagellum had the strongest influence on its static biomechanical behaviour. The annulated structure and thickness gradient affected the deformability of the flagellum to a lesser degree. The inner endocuticle layer of the flagellum was confirmed to be essential for explaining the strongly damped return behaviour of the antenna. By highlighting the significance of two out of the four main structural features of the insect flagellum, our study provides a basis for mechanical design of biomimetic touch sensors tuned to become maximally flexible while quickly resuming a straight shape after contact.
Neutral lineage tracing of proliferative embryonic and adult mammary stem/progenitor cells

ABSTRACT Mammary gland development occurs over multiple phases, beginning in the mammalian embryo and continuing throughout reproductive life. The remarkable morphogenetic capacity of the mammary gland at each stage of development is attributed to the activities of distinct populations of mammary stem cells (MaSCs) and progenitor cells. However, the relationship between embryonic and adult MaSCs, and their fate during different waves of mammary gland morphogenesis, remains unclear. By employing a neutral, low-density genetic labelling strategy, we characterised the contribution of proliferative stem/progenitor cells to embryonic, pubertal and reproductive mammary gland development. Our findings further support a model of lineage restriction of MaSCs in the postnatal mammary gland, and highlight extensive redundancy and heterogeneity within the adult stem/progenitor cell pool. Furthermore, our data suggest extensive multiplicity in their foetal precursors that give rise to the primordial mammary epithelium before birth. In addition, using a single-cell labelling approach, we revealed the extraordinary capacity of a single embryonic MaSC to contribute to postnatal ductal development. Together, these findings provide tantalising new insights into the disparate and stage-specific contribution of distinct stem/progenitor cells to mammary gland development. Summary: Neutral, low-density lineage tracing of proliferative mammary stem and progenitor cells during embryonic, pubertal and reproductive mammary gland development reveal the disparate and stage-specific contribution of distinct stem/progenitor cells.
The Natural Rotenoid Deguelin Ameliorates Diabetic Neuropathy by Decreasing Oxidative Stress and Plasma Glucose Levels in Rats via the Nrf2 Signalling Pathway

Background/Aims: Deguelin is a natural rotenoid that shows anti-inflammatory and antimicrobial activities. Rotenoids prevent oxidative damage and potentiate natural antioxidant activity in diabetic conditions, suggesting utility in treating diabetes and its complications. Here, we evaluate the potential efficacy of deguelin against diabetic neuropathy (DN). Methods: DN was induced by streptozotocin followed by daily treatment with deguelin (4, 6 or 8 mg/kg) for 14 days. Blood glucose was measured, neurobehavioral tests for nociception and motor coordination were performed, and neuron conduction velocities were analysed electrophysiologically. We also assessed (Na+-K+) ATPase activity, performed a reactive oxygen species assay, measured the levels of various markers of oxidative stress, and of hydrogen sulphide (H2S) in dorsal root ganglion (DRG) neurons, conducted immunoblotting studies for proteins and ELISA for inflammatory cytokines. Results: Deguelin significantly suppressed mechanical and thermal hyperalgesia, as well as cold allodynia, and partially restored the conduction velocities of neurons in DN rats. Significantly decreased expression levels of capspase-3 in DRG neurons, and increased (Na+-K+) ATPase activity in sciatic nerves, were observed. In addition, deguelin decreased glucose levels, attenuated oxidative stress and neuroinflammation, and elevated levels of H2S, nuclear respiratory factor 2 (Nrf2) and heme oxygenase-1, suggesting a disease-attenuating effect of deguelin in DN rats. To shed light on the underlying mechanism of action of deguelin, insulin- and dimethyl fumarate (BG-12)-treated groups were also included. Insulin suppressed glucose levels and BG-12 produced effects on Nrf2 levels similar to 8 mg/kg deguelin, confirming involvement of the Nrf2 pathway in the beneficial effects of deguelin against DN. Conclusions: Deguelin attenuated DN by decreasing oxidative stress and plasma glucose levels via the Nrf2 signalling pathway.
Predicting Head Movement in Panoramic Video: A Deep Reinforcement Learning Approach

Panoramic video provides immersive and interactive experience by enabling humans to control the field of view (FoV) through head movement (HM). Thus, HM plays a key role in modeling human attention on panoramic video. This paper establishes a database collecting subjects’ HM in panoramic video sequences. From this database, we find that the HM data are highly consistent across subjects. Furthermore, we find that deep reinforcement learning (DRL) can be applied to predict HM positions, via maximizing the reward of imitating human HM scanpaths through the agent's actions. Based on our findings, we propose a DRL-based HM prediction (DHP) approach with offline and online versions, called offline-DHP and online-DHP. In offline-DHP, multiple DRL workflows are run to determine potential HM positions at each panoramic frame. Then, a heat map of the potential HM positions, named the HM map, is generated as the output of offline-DHP. In online-DHP, the next HM position of one subject is estimated given the currently observed HM position, which is achieved by developing a DRL algorithm upon the learned offline-DHP model. Finally, the experiments validate that our approach is effective in both offline and online prediction of HM positions for panoramic video, and that the learned offline-DHP model can improve the performance of online-DHP.