Miracle-dz/UniFAR-FTUs huggingface dataset:
The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural china

We previously reported that bacterial diversity in sputum samples from never‐smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never‐smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1–V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high‐quality sequences were evaluated for diversity and taxonomic membership. In our population of never‐smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02–14.48], ORlow = 3.78 [1.03–13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67–8.48], ORlow = 2.01 [0.58–6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85–10.92], ORlow = 2.53 [0.72–8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42–3.66], ORlow = 2.01 [0.63–6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease‐specific, HAP‐specific, and animal‐specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.
Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation

Receptor activator of NF-kappaB ligand (RANKL) plays an essential role in osteoclast formation and bone resorption. Although genetic and biochemical studies indicate that RANKL regulates osteoclast differentiation by activating receptor activator of NF-kappaB and associated signaling molecules, the molecular mechanisms of RANKL-regulated osteoclast differentiation have not yet been fully established. We investigated the role of the transcription factor c-Jun, which is activated by RANKL, in osteoclastogenesis using transgenic mice expressing dominant-negative c-Jun specifically in the osteoclast lineage. We found that the transgenic mice manifested severe osteopetrosis due to impaired osteoclastogenesis. Blockade of c-Jun signaling also markedly inhibited soluble RANKL-induced osteoclast differentiation in vitro. Overexpression of nuclear factor of activated T cells 1 (NFAT1) (NFATc2/NFATp) or NFAT2 (NFATc1/NFATc) promoted differentiation of osteoclast precursor cells into tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated osteoclast-like cells even in the absence of RANKL. Overexpression of NFAT1 also markedly transactivated the TRAP gene promoter. These osteoclastogenic activities of NFAT were abrogated by overexpression of dominant-negative c-Jun. Importantly, osteoclast differentiation and induction of NFAT2 expression by NFAT1 overexpression or soluble RANKL treatment were profoundly diminished in spleen cells of the transgenic mice. Collectively, these results indicate that c-Jun signaling in cooperation with NFAT is crucial for RANKL-regulated osteoclast differentiation.
Risk factors associated with clinical outcomes of endoscopic mucosal resection for colorectal laterally spreading tumors: A Honam Association for the Study of Intestinal Diseases (HASID) multicenter study.

BACKGROUND/AIMS Colorectal laterally spreading tumors (LSTs) are large and superficial neoplasms. Most are adenomatous lesions. Endoscopic mucosal resection (EMR) is a standard technique of removing precursor colorectal lesions. The aim of the present study was to assess the factors associated with the clinical outcomes of EMR for LSTs. MATERIALS AND METHODS A total of 275 patients with LSTs who underwent EMR were enrolled in the study. The clinical outcomes of the patients were analyzed by retrospectively reviewing their medical records. RESULTS The en bloc resection and R0 resection rates were 86.9% and 80.4%, respectively. The bleeding and perforation rates were 7.6% and 0.4%, respectively. The frequency of high-grade dysplasia and adenocarcinoma histology was significantly higher, and the procedure time was significantly longer in LSTs >20 mm than in those ≤20 mm. The R0 resection rate was significantly higher in LSTs ≤20 mm than in those >20 mm. The frequency of piecemeal resection was significantly higher in LSTs with an adenomatous and cancerous pit pattern than in those with a non-neoplastic pit pattern. The frequency of piecemeal resection was significantly higher in LSTs with adenocarcinoma than in those with low-grade dysplasia. Multivariate analysis revealed that adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma was a significant independent risk factor of LSTs for piecemeal resection after EMR. CONCLUSION EMR is useful for treating ≤20 mm LSTs with regard to curative resection and procedure time. LSTs with an adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma are significant independent risk factors for piecemeal resection after EMR.
The influence of an anti‐inflammatory diet on gingivitis. A randomized controlled trial

AIM Aim of this study was to investigate the influence of an anti-inflammatory diet on different parameters in patients with gingivitis. MATERIALS AND METHODS Thirty patients were randomly allocated to an experimental and a control group stratified by their plaque values. The experimental group had to change to a diet low in processed carbohydrates and animal proteins, and rich in omega-3 fatty acids, vitamin C, vitamin D, antioxidants, plant nitrates and fibres for 4 weeks. The control group did not change their diet. Both groups suspended interdental cleaning. Periodontal parameters were assessed by a blinded dentist. Serological and subgingival plaque samples were taken at baseline and end. RESULTS While there were no differences regarding the plaque values, the experimental group showed a significant reduction in gingival bleeding (GI Baseline: 1.04 ± 0.21, GI End: 0.61 ± 0.29, p < 0.05), a significant increase in Vitamin D values and a significant weight loss. There were no inter-group differences regarding the inflammatory serological parameters, the serological omega fatty acids, nor the subgingival microbiome composition. CONCLUSION The evaluated diet could significantly reduce gingivitis in a clinically relevant range, while serological inflammatory parameters and the subgingival microbiome seem to be unaffected in this study duration. (German Clinical Trials Register; DRKS00009888).
Moringa oleifera Aqueous Leaf Extract Induces Cell-Cycle Arrest and Apoptosis in Human Liver Hepatocellular Carcinoma Cells

Abstract Aim: Hepatocellular carcinoma is one of the leading global epidemics. A medicinal tree, Moringa oleifera (MO), has been part of traditional treatments including cancer therapies. We investigated the apoptosis inducing effects of MO crude aqueous leaf extract (MOE) in human liver hepatocellular carcinoma (HepG2) cells. Methods: HepG2, PBMCs and Hek293 cell viability was evaluated using MTT assay. Oxidative stress and DNA damage was determined using TBARS and comet assays, respectively. Apoptosis was assessed by caspase-9, -3/7 activities and ATP levels (luminometry). Cell cycle, γH2AX, and cleaved PARP-1 were determined (flow cytometry). Protein expression of c-myc, Bax, p-Bcl2, Smac/DIABLO, Hsp70, SRp30a and cleaved PARP-1 was assessed using western blotting. Results: MOE displayed minimal toxicity in PBMCs and Hek293 cells for 24 h. HepG2 cells were exposed to MOE (24 h) and an IC50 (4.479 mg/mL) was determined. MOE significantly increased lipid peroxidation, DNA damage and γH2AX levels. A significant decrease in G1, S and G2-M phase was seen. Significant increase in SRp30a protein expression activated caspase-9. Caspase-9 and -3/7 was significantly increased with significant decrease in ATP levels. Apoptosis was confirmed with significant decrease in c-myc, p-Bcl2 and Hsp70 protein expression and a significant increase in Bax, Smac/DIABLO and PARP-1 cleavage. Conclusion: MOE induces cell-cycle arrest and apoptosis in cancerous HepG2 cells.
Tattoo free setup for partial breast irradiation: A feasibility study

Abstract Purpose Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three‐dimensional (3D) body surface imaging and two‐dimensional (2D) x‐ray imaging‐based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo‐based setups to a patient setup without tattoos. Materials/methods Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x‐ray‐based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. Results Among ten patients in the “no tattoo” group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the “no tattoo” group were 4.6 vs 5.9 mm in the “tattoo” cohort (P = NS). Mean systematic errors in the “no tattoo” group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the “tattoo” group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the “no tattoo” group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the “tattoo” group. Conclusions Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin‐based tattoos may no longer be warranted for patients receiving external beam APBI.
Characterization of human skin equivalents developed at body's core and surface temperatures

Human skin equivalents (HSEs) are in vitro developed three‐dimensional models resembling native human skin (NHS) to a high extent. However, the epidermal lipid biosynthesis, barrier lipid composition, and organization are altered, leading to an elevated diffusion rate of therapeutic molecules. The altered lipid barrier formation in HSEs may be induced by standardized culture conditions, including a culture temperature of 37°C, which is dissimilar to skin surface temperature. Therefore, we aim to determine the influence of culture temperature during the generation of full thickness models (FTMs) on epidermal morphogenesis and lipid barrier formation. For this purpose, FTMs were developed at conventional core temperature (37°C) or lower temperatures (35°C and 33°C) and evaluated over a time period of 4 weeks. The stratum corneum (SC) lipid composition was analysed using advanced liquid chromatography coupled to mass spectrometry analysis. Our results show that SC layers accumulated at a similar rate irrespective of culture temperature. At reduced culture temperature, an increased epidermal thickness, a disorganization of the lower epidermal cell layers, a delayed early differentiation, and an enlargement of granular cells were detected. Interestingly, melanogenesis was reduced at lower temperature. The ceramide subclass profile, chain length distribution, and level of unsaturated ceramides were similar in FTMs generated at 37°C and 35°C but changed when generated at 33°C, reducing the resemblance to NHS. Herein, we report that culture temperature affects epidermal morphogenesis substantially and to a lesser extent the lipid barrier formation, highlighting the importance of optimized external parameters during reconstruction of skin.
Concordance of Self- and Clinician-Collected Anal Swabs to Detect Human Papillomavirus in a Sample of HIV-Negative Men.

OBJECTIVE The aim of this study was to determine the concordance of self- and clinician-collected anorectal swabs for the detection of human papillomavirus (HPV) DNA in a population of HIV-negative men who have sex with men (MSM). METHODS This cross-sectional study involved recruitment of HIV-negative MSM in a Midwestern US metropolitan area to collect paired sequential self- and clinician-collected anorectal swabs using illustrated instructions. Swabs were tested for type-specific HPV DNA with a comparison of type-specific HPV categories detected by each method. The sensitivity and specificity of self-collection were calculated assuming clinician collection as the criterion standard. McNemar's test and κ statistics were used to determine percent agreement and concordance of self- and clinician-collected swab results. RESULTS Seventy-eight participants had paired anorectal swab samples of adequate quality for analyses. The sensitivity and specificity of self-collected swabs for detection of all high-risk HPV DNA types were 69.8% and 91.4%, respectively. Similar degrees of sensitivity and specificity of self-collection were seen for other groups of high-risk HPV types. Percent agreement and κ statistic for self- and clinician-collected swabs for all high-risk HPV types were 80.8% and 0.53, respectively. CONCLUSIONS Self-collected anorectal swab samples showed lower sensitivity but moderate to high specificity for detection of high-risk and vaccine-preventable HPV types compared with clinician-collected swab samples. Self-collection instructional details and the thoroughness of clinician collection of samples may have impacted sensitivity and specificity, suggesting a need to optimize and standardize instructions.
Associations between empathy and altruistic sharing behavior in Chinese adults

Abstract Previous research has shown that affective empathy, rather than cognitive empathy, significantly predicts people’s altruistic sharing behavior in economic games. However, most of these studies were conducted in Western populations. There might be cultural differences in the relations between empathy and altruism due to different levels of empathy between Western and Asian individuals. In this study, we measured different aspects of empathy in Chinese adults as well as their allocation offers in the dictator and ultimatum games. We found that cognitive empathy, but not affective empathy, was a significant predictor of adults’ altruistic sharing behavior in the two economic games. Subjective family income was also revealed to be a significant predictor of individuals’ altruism in the ultimatum game, such that people with lower subjective family income tended to be more generous. Potential implications of our findings are discussed.
Validity and Reliability of Firefighting Simulation Test Performance.

OBJECTIVE To assess the validity and reliability of a firefighting simulation test (FFST). METHODS Sixty-nine operational firefighters completed a best-effort FFST on one occasion and 22 participants completed a further FFST. All participants completed a maximal treadmill test to determine cardiorespiratory fitness (VO2max). RESULTS Time to complete the FFST demonstrated a strong inverse relationship with VO2max (r = -0.73), although the prediction error was high. Reliability of the FFST was high (r = 0.84, P = 0.01), demonstrating a coefficient of variation of 4.5%. CONCLUSIONS The FFST demonstrated reasonable validity as a surrogate assessment of cardiorespiratory fitness for firefighting. The FFST also demonstrated good reliability. Given the apparent magnitude of the prediction error, the FFST would be best used as a training tool, rather than as a primary means of assessing cardiorespiratory fitness for firefighting.
Automated individualization of dialysate sodium concentration reduces intradialytic plasma sodium changes in hemodialysis

Abstract In standard care, hemodialysis patients are often treated with a center‐specific fixed dialysate sodium concentration, potentially resulting in diffusive sodium changes for patients with plasma sodium concentrations below or above this level. While diffusive sodium load may be associated with thirst and higher interdialytic weight gain, excessive diffusive sodium removal may cause intradialytic symptoms. In contrast, the new hemodialysis machine option “Na control” provides automated individualization of dialysate sodium during treatment with the aim to reduce such intradialytic sodium changes without the need to determine the plasma sodium concentration. This proof‐of‐principle study on sodium control was designed as a monocentric randomized controlled crossover trial: 32 patients with residual diuresis of ≤1000 mL/day were enrolled to be treated by high‐volume post‐dilution hemodiafiltration (HDF) for 2 weeks each with “Na control” (individually and automatically adjusted dialysate sodium concentration) versus “standard fixed Na” (fixed dialysate sodium 138 mmol/L), in randomized order. Pre‐ and post‐dialytic plasma sodium concentrations were determined at bedside by direct potentiometry. The study hypothesis consisted of 2 components: the mean plasma sodium change between the start and end of the treatment being within ±1.0 mmol/L for sodium‐controlled treatments, and a lower variability of the plasma sodium changes for “Na control” than for “standard fixed Na” treatments. Three hundred seventy‐two treatments of 31 adult chronic hemodialysis patients (intention‐to‐treat population) were analyzed. The estimate for the mean plasma sodium change was −0.53 mmol/L (95% confidence interval: [−1.04; −0.02] mmol/L) for “Na control” treatments and −0.95 mmol/L (95% CI: [−1.76; −0.15] mmol/L) for “standard fixed Na” treatments. The standard deviation of the plasma sodium changes was 1.39 mmol/L for “Na control” versus 2.19 mmol/L for “standard fixed Na” treatments (P = 0.0004). Whereas the 95% CI for the estimate for the mean plasma sodium change during “Na control” treatments marginally overlapped the lower border of the predefined margin ±1.0 mmol/L, the variability of intradialytic plasma sodium changes was lower during “Na control” versus “standard fixed Na” treatments. Thus, automated dialysate sodium individualization by “Na control” approaches isonatremic dialysis in the clinical setting.
Ensemble Robustness and Generalization of Stochastic Deep Learning Algorithms

The question why deep learning algorithms generalize so well has attracted increasing research interest. However, most of the well-established approaches, such as hypothesis capacity, stability or sparseness, have not provided complete explanations (Zhang et al., 2016; Kawaguchi et al., 2017). In this work, we focus on the robustness approach (Xu & Mannor, 2012), i.e., if the error of a hypothesis will not change much due to perturbations of its training examples, then it will also generalize well. As most deep learning algorithms are stochastic (e.g., Stochastic Gradient Descent, Dropout, and Bayes-by-backprop), we revisit the robustness arguments of Xu & Mannor, and introduce a new approach, ensemble robustness, that concerns the robustness of a population of hypotheses. Through the lens of ensemble robustness, we reveal that a stochastic learning algorithm can generalize well as long as its sensitiveness to adversarial perturbations is bounded in average over training examples. Moreover, an algorithm may be sensitive to some adversarial examples (Goodfellow et al., 2015) but still generalize well. To support our claims, we provide extensive simulations for different deep learning algorithms and different network architectures exhibiting a strong correlation between ensemble robustness and the ability to generalize.
miR‐124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast‐like synoviocytes via targeting PIK3/NF‐κB pathway

Abnormal hyperplasia of fibroblast‐like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR‐124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF‐κB in RAFLS was examined by real‐time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 was detected by ELISA. The joint swelling and inflammation in collagen‐induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR‐124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR‐124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR‐124a inhibited the expression of the key components of the PIK3/Akt/NF‐κB signal pathway and inhibited the expression of pro‐inflammatory factors TNF‐α and IL‐6. Local overexpression of miR‐124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR‐124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF‐κB pathway. miR‐124a is a promising therapeutic target for RA.
A computational observer model of spatial contrast sensitivity: Effects of wavefront-based optics, cone mosaic structure, and inference engine

We present a computational observer model of the human spatial contrast sensitivity (CSF) function based on the Image Systems EngineeringTools for Biology (ISETBio) simulation framework. We demonstrate that ISETBio-derived CSFs agree well with CSFs derived using traditional ideal observer approaches, when the mosaic, optics, and inference engine are matched. Further simulations extend earlier work by considering more realistic cone mosaics, more recent measurements of human physiological optics, and the effect of varying the inference engine used to link visual representations to psy-chohysical performance. Relative to earlier calculations, our simulations show that the spatial structure of realistic cone mosaics reduces upper bounds on performance at low spatial frequencies, whereas realistic optics derived from modern wavefront measurements lead to increased upper bounds high spatial frequencies. Finally, we demonstrate that the type of inference engine used has a substantial effect on the absolute level of predicted performance. Indeed, the performance gap between an ideal observer with exact knowledge of the relevant signals and human observers is greatly reduced when the inference engine has to learn aspects of the visual task. ISETBio-derived estimates of stimulus representations at different stages along the visual pathway provide a powerful tool for computing the limits of human performance.