Miracle-dz/UniFAR-FTUs huggingface dataset:
Central Tumor Location at Chest CT Is an Adverse Prognostic Factor for Disease-Free Survival of Node-Negative Early-Stage Lung Adenocarcinomas.

Background The prognostic value of primary tumor location in the central lung is unclear because of heterogeneity in definitions of central lung cancer (CLC). Purpose To (a) validate the prognostic value of two recently proposed definitions of CLC by using a method designed to offset the shortcomings of existing evidence and (b) investigate the prognostic implications of a quantitative definition of CLC at chest CT. Materials and Methods Patients with pathologic stage T1a-bN0M0 lung adenocarcinomas resected between 2009 and 2015 at a single tertiary care center were retrospectively identified. The primary end point was disease-free survival. The associations of multiple definitions of central tumor location with survival were evaluated by using multivariable Cox regression. Time-dependent discrimination measures and interreader agreement were assessed for each definition. Results A total of 436 patients (median age, 62 years [interquartile range, 55-69 years]; 245 women) were evaluated. Tumor location at CT in the inner one-third of the lung defined by concentric lines arising from the hilum was adversely associated with survival (five events among 34 patients with CLC and 27 events among 402 patients with peripheral lung cancer; adjusted hazard ratio, 2.90 [95% CI: 1.06, 7.96; P = .04]) and showed moderate interreader agreement (Cohen κ = 0.52 [95% CI: 0.37, 0.68]). Quantitatively determined location in the inner two-thirds of the lung was also an independent prognostic factor (16 events among 130 patients with CLC and 16 events among 306 patients with peripheral lung cancer; adjusted hazard ratio, 2.77 [95% CI: 1.36, 5.65]; P = .005), with higher interreader agreement (Cohen κ = 0.86 [95% CI: 0.80, 0.91]; P < .001). The quantification-based definition exhibited higher time-dependent sensitivity (48.2% [14.27/29.61; 95% CI: 28.8, 67.6] vs 15.1% [4.47/29.61; 95% CI: 1.3, 28.9]; P < .001). Conclusion Central lung cancer at chest CT, defined qualitatively or quantitatively, is an independent adverse prognostic factor in patients with node-negative, early-stage lung adenocarcinomas. The quantification-based approach has advantages in terms of time-dependent sensitivity and reproducibility. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wandtke and Hobbs in this issue.
Impact of area deprivation on the cardiac mortality in the UK between1991 and 2010: evidence from a population-based longitudinal study.

AIMS Evidence from longitudinal studies on the influence of area deprivation in cardiac mortality is limited. We aimed to examine the impact of area deprivation on cardiac mortality in a large representative Scottish population. We also examined differences between women and men. METHODS AND RESULTS Retrospective analysis was performed by using linked data from Scottish Longitudinal Study from 1991 to 2010. The main exposure variable was socioeconomic status using the Carstairs deprivation scores, a composite score of area-level factors. Cox proportional-hazards models were constructed to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiac mortality and all-cause mortality associated with area-based deprivation. Subgroup analyses were stratified by sex. In a representative population of 217 965 UK adults, a total of 58 770 deaths occurred over a median of 10 years of follow-up period. The risk of cardiac mortality and all-cause mortality showed a consistent graded increased across the deprived groups. Compared to the least deprived group, the adjusted HR of cardiac mortality in the most deprived group was 1.27 (1.15-1.39, P < 0.000). There was strong evidence that women from more deprived areas had significantly higher cardiac death risk than those from the least deprived areas (HR 1.42, 95% CI 1.22-1.65), while this observation was not strong in men with same background. CONCLUSION Our study demonstrated area deprivation was the strong predictor of long-term cardiac mortality and all-cause mortality. The inequalities were substantially greater in women from more deprived areas than men from the same background.
Effect of the initial soil water saturation on the behaviour of a mixed LNAPL and heavy metal contaminated glaciofluvial deposit

Soil contamination by mixtures of petroleum hydrocarbons and heavy metals is common in urban and industrial localities. Interactions between these contaminants have an impact on the mobility and the management of contamination. We have characterized the modifications to the transport of heavy metals (Cd, Cu, Pb, Zn) in soil induced by residual light non‐aqueous phase liquid (LNAPL) for two conditions of trapping. Experiments on the elution of tracers and heavy metals in columns of soil were performed with a glaciofluvial material as the soil. Tracer experiments were modelled with the mobile–immobile (MIM) system of partial differential equations. The experiments were designed to compare water flow and metal transport in LNAPL‐contaminated soil with a control set. Residual LNAPL was trapped in water‐saturated and dry soil to ensure preferential wettability of soil surfaces, namely either water‐wet or LNAPL‐wet.
Suppression of food restriction‐evoked hyperactivity in activity‐based anorexia animal model through glutamate transporters GLT‐1 at excitatory synapses in the hippocampus

Severe voluntary food restriction is the defining symptom of anorexia nervosa (AN), but anxiety and excessive exercise are maladaptive symptoms that contribute significantly to the severity of AN and which individuals with AN have difficulty suppressing. We hypothesized that the excitability of hippocampal pyramidal neurons, known to contribute to anxiety, leads to the maladaptive behavior of excessive exercise. Conversely, since glutamate transporter GLT‐1 dampens the excitability of hippocampal pyramidal neurons through the uptake of ambient glutamate and suppression of the GluN2B‐subunit containing NMDA receptors (GluN2B‐NMDARs), GLT‐1 may contribute toward dampening excessive exercise. This hypothesis was tested using the mouse model of AN, called activity‐based anorexia (ABA), whereby food restriction evokes the maladaptive behavior of excessive wheel running (food restriction‐evoked running, FRER). We tested whether individual differences in ABA vulnerability of mice, quantified based on FRER, correlated with individual differences in the levels of GLT‐1 at excitatory synapses of the hippocampus. Electron microscopic immunocytochemistry (EM‐ICC) was used to quantify GLT‐1 levels at the excitatory synapses of the hippocampus. The FRER seen in individual mice varied more than 10‐fold, and Pearson correlation analyses revealed a strong negative correlation (p = .02) between FRER and GLT‐1 levels at the axon terminals of excitatory synapses and at the surrounding astrocytic plasma membranes. Moreover, synaptic levels of GluN2B‐NMDARs correlated strongly with GLT‐1 levels at perisynaptic astrocytic plasma membranes. There is at present no accepted pharmacotherapy for AN, and little is known about the etiology of this deadly illness. Current findings suggest that drugs increasing GLT‐1 expression may reduce AN severity through the reduction of GluN2B‐NMDAR activity.
Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis

Background Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. Objectives The aim of our study was to determine the association of these markers’ serum levels on lung function and the patients’ quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. Methods 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. Results Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. Conclusions Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.
Changes in the Foveal Avascular Zone Area and Retinal Vessel Density after Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration

ABSTRACT Purpose To investigate changes in the foveal avascular zone (FAZ) area and retinal vessel density (VD) in the macula of patients receiving multiple anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (N-AMD). Methods This study included 54 eyes of 54 treatment-naïve N-AMD patients. Thirty-three eyes were treated with intravitreal aflibercept injections, and 21 eyes were treated with intravitreal ranibizumab injections. Unaffected fellow eyes (54 eyes) were used as controls. All image scans were acquired after the macular architecture had recovered with drying up of the subretinal fluid/hemorrhage after treatment. Results Both the superficial and deep FAZ areas were significantly larger in the aflibercept group than in the control group. The VD was also significantly reduced in the aflibercept group. Conclusions Prolonged and repeated anti-VEGF therapy may cause an increase in the FAZ area and a decrease in the VD in patients with N-AMD, indicating ischemic damage.
Effects of Smartphone-Based Stress Management on Improving Work Engagement Among Nurses in Vietnam: Secondary Analysis of a Three-Arm Randomized Controlled Trial

Background Work engagement is important for employee well-being and work performance. However, no intervention study has investigated the effect of an eMental Health intervention on work engagement among workers in low- and middle-income countries (LMICs). Objective The aim of the study was to examine the effects of a newly developed smartphone-based stress management program (ABC Stress Management) on improving work engagement among hospital nurses in Vietnam, an LMIC. Methods Full-time registered nurses (n=949) were randomly assigned to one of 2 intervention groups or a control group. The intervention groups were a 6-week, 6-lesson program offering basic cognitive behavioral therapy (CBT-based stress management skills), provided in either free-choice (program A) or fixed order (program B). Work engagement was assessed at baseline and 3-month and 7-month follow-ups in each of the 3 groups. Results The scores of work engagement in both intervention groups improved from baseline to 3-month follow-up, and then decreased at the 7-month follow-up, while the score steadily increased from baseline to 7-month follow-up in the control group. Program B showed a significant intervention effect on improving work engagement at the 3-month follow-up (P=.049) with a small effect size (Cohen d= 0.16; 95% CI 0.001 to 0.43]). Program A showed nonsignificant trend (d=0.13; 95% CI –0.014 to 0.41; P=.07) toward improved engagement at 3 months. Neither program achieved effectiveness at the 7-month follow-up. Conclusions The study demonstrated that a fixed order (program B) delivery of a smartphone-based stress management program was effective in improving work engagement in nurses in Vietnam. However, the effect was small and only temporary. Further improvement of this program is required to achieve a greater effect size and more sustained, longer lasting impact on work engagement. Trial Registration University Hospital Medical Information Network Clinical Trials Registry UMIN000033139; tinyurl.com/55gxo253 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2018-025138
On kernel machine learning for propensity score estimation under complex confounding structures

Post marketing data offer rich information and cost‐effective resources for physicians and policy‐makers to address some critical scientific questions in clinical practice. However, the complex confounding structures (e.g., nonlinear and nonadditive interactions) embedded in these observational data often pose major analytical challenges for proper analysis to draw valid conclusions. Furthermore, often made available as electronic health records (EHRs), these data are usually massive with hundreds of thousands observational records, which introduce additional computational challenges. In this paper, for comparative effectiveness analysis, we propose a statistically robust yet computationally efficient propensity score (PS) approach to adjust for the complex confounding structures. Specifically, we propose a kernel‐based machine learning method for flexibly and robustly PS modeling to obtain valid PS estimation from observational data with complex confounding structures. The estimated propensity score is then used in the second stage analysis to obtain the consistent average treatment effect estimate. An empirical variance estimator based on the bootstrap is adopted. A split‐and‐merge algorithm is further developed to reduce the computational workload of the proposed method for big data, and to obtain a valid variance estimator of the average treatment effect estimate as a by‐product. As shown by extensive numerical studies and an application to postoperative pain EHR data comparative effectiveness analysis, the proposed approach consistently outperforms other competing methods, demonstrating its practical utility.
Biomonitorization of concentrations of 28 elements in serum and urine among workers exposed to indium compounds

Many studies have documented the abnormal concentrations of metals/metalloids in serum or urine of occupational workers, but no works systematically analysed the concentrations of elements in serum or urine of indium-exposed workers. This study was aimed to assess 28 elements in serum and urine from 57 individuals with occupational exposure to indium and its compounds. Control subjects were 63 workers without metal exposure. We collected information on occupation and lifestyle habits by questionnaire. Biological samples were collected to quantify elements by inductive coupled plasma-mass spectrometer. Air in the breathing zones was drawn at flow rates of 1.5–3 L/min for a sampling period of 6 to 8 h, using a Model BFC-35 pump. The average ambient indium level was 0.078 mg/m3. Serum/urine Indium levels were significantly higher in indium-exposed workers than in controls (P < 0.01). Moreover, serum/urine indium concentrations in the group with 6–14 years and ≥15 years of employment were significantly higher than those with ≤5 employment years(P < 0.05). Ten of the other 27 elements/metals measured were higher in serum/urine in indium-exposed workers compared to the controls (aluminum, beryllium, cadmium, cesium, chromium, lithium, manganese, magnesium, molybdenum and vanadium). Zinc levels in serum/urine were significantly decreased in the indium-exposed workers. Additionally, other elements/metals were higher in one specimen (serum or urine) but lower in the other (Selenium was lower in serum but higher in urine in the indium-exposed workers compared with the controls; likewise Thallium and Rubidium were higher in serum but lower in urine). Linear regression analyses, revealed significant correlations between serum and urine for indium, aluminum, arsenic, barium, cadmium, cesium, cobalt, selenium, silver, and zinc (P < 0.05). These data suggest that occupational exposure to indium and its compounds may disturb the homeostasis of trace elements in systemic circulation, indium concentrations in serum or urine appear reflective of workers’ exposure to ambient indium and their years of working, respectively. The serum/urine levels of essential metals are modified by exposure to indium in occupationally exposed workers. Further studies including larger sample size and more kinds of biological sample are needed to validate our findings.
Biomechanics of the fresh and conserved bovine pericardium

The use of biological membranes in surgeries is a reality for years, and one of the most used is the bovine pericardium, so the purpose of this research is to describe the bovine pericardium's biomechanics by comparing two directions of a test, one parallel to the longitudinal heart axis and one perpendicular. 20 adult bovine pericardium were tested for the maximum rupture force and rupture elongation, collecting four samples of each pericardium direction. In phase 2, eight pericardia were conserved for 4 months in a 98% glycerine solution, and the solution in which they were submerged was microbiologically analysed monthly. The Mann–Whitney test was used; there was a very significant difference between the perpendicular and parallel groups (p = .0001). The T test showed no significant difference for the rupture elongation (p = .0938). In pericardium preserved in glycerine, the outliers were removed regarding the maximum rupture force, and a Boxcox transformation was performed (λ = 0.25). Outliers were removed for the rupture elongation, and Bartlett's test (p = .7836), and Cramer–Von Mises (p = .5033) were performed and then, the analysis of variance (p < .0001), followed by the Tukey test at 5%. In the microbiological analysis, there was no presence of microorganisms during conservation. The research has shown that the pericardium collection direction influences its resistance and it can be stored in glycerine for 4 months without losing biomechanical characteristics.
Circulating microparticles and activated platelets as novel prognostic biomarkers in COVID-19; relation to cancer

Background and aim The study aimed to determine whether the MPs levels and platelet activation are affected by the COVID-19 infection in both malignant and non-malignant patients compared to healthy individuals and define their contribution to the COVID-19 associated coagulopathy and the relation of these MPs to other hematologic parameters. Patients and methods We recruited 23 malignant patients with reverse transcription polymerase chain reaction (RT-PCR) positive COVID-19, also, 19 COVID-19 non-malignant patients, and 20 healthy volunteers were also enrolled for comparison. Blood samples were collected from patients and healthy donors into 5 mL vacutainer tube containing 3.5% buffered sodium citrate solution for measurement of total microparticles (TMPs), platelet microparticles (PMPs), endothelial microparticles (EMPs), CD62 activated platelets, and CD41 platelet marker. Results COVID-19 malignant patients had significantly lower hemoglobin and platelets compared to COVID non-malignant ones, while they had significantly higher C-reactive protein, LDH, AST, Albunim, creatinine, and prognostic index (PI) compared to COVID-19 non-malignant patients. significant accumulations of TMPs, PMPs, EMPs, and activated platelets in COVID-19 affected patients compared to healthy controls. TMPs, and EMPs were significantly accumulated in COVID-19 malignant compared to COVID-19 non-malignant patients with no significant difference in PMPs between both. Conclusion Circulating MPs and activated platelets may be promising novel prognostic biomarkers capable of identifying potentially severe COVID-19 patients who require immediate care especially in cancer patients.
Effects of urolithins on obesity-associated gut dysbiosis in rats fed on a high-fat diet

Abstract Obesity is a global health concern associated with the dysbiosis of intestinal microbial composition. In this study, we investigated the potentials of urolithin A (Uro-A) and urolithin B (Uro-B), two gut microbiota-derived metabolites of ellagitannins, in reducing body weight gain through the modulation of the gut microbiota. We established a high-fat diet (HFD)-induced obesity model in rats that were later administered with either 2.5 mg/kg of Uro-A or Uro-B. Serum biochemical parameters were quantified, and changes in the composition of the gut microbial community were analysed using 16S rDNA gene sequencing. Our results showed that the urolithins significantly decreased the body weight in HFD-fed rats and restored serum lipid profile. The taxonomic analysis showed that both Uro-A and Uro-modulated gut microbes related to body weight, dysfunctional lipid metabolism and inflammation. Overall, our results suggest that Uro-A and Uro-B possess anti-obesity properties, which may be related to the modulation of the gut microbial composition. Graphical Abstract
Different functional roles of RTR complex factors in DNA repair and meiosis in Arabidopsis and tomato.

The RTR (RecQ/Top3/Rmi1) complex has been elucidated as essential for ensuring genome stability in eukaryotes. Fundamental for the dissolution of Holliday junction (HJ)-like recombination intermediates, the factors have been shown to play further, partly distinct roles in DNA repair and homologous recombination. Across all kingdoms, disruption of this complex results in characteristic phenotypes including hyperrecombination and sensitivity to genotoxins. The type IA topoisomerase TOP3α has been shown as essential for viability in various animals. In contrast, in the model plant species Arabidopsis, the top3α mutant is viable. rmi1 mutants are deficient in the repair of DNA damage. Moreover, as opposed to other eukaryotes, TOP3α and RMI1 were found to be indispensable for proper meiotic progression, with mutants showing severe meiotic defects and sterility. We now established mutants of both TOP3α and RMI1 in tomato using CRISPR/Cas technology. Surprisingly, we found phenotypes that differed dramatically from those of Arabidopsis: The top3α mutants proved to be embryo-lethal, implying an essential role of the topoisomerase in tomato. In contrast, no defect in somatic DNA repair or meiosis was detectable for rmi1 mutants in tomato. This points to a differentiation of function of RTR complex partners between plant species. Our results indicate that there are relevant differences in the roles of basic factors involved in DNA repair and meiosis within dicotyledons, and thus should be taken as a note of caution when generalising knowledge regarding basic biological processes obtained in the model plant Arabidopsis for the entire plant kingdom.