Miracle-dz/UniFAR-FTUs huggingface dataset:
Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography

Many important gram-negative bacterial pathogens use highly sophisticated type III secretion systems (T3SSs) to establish complex host-pathogen interactions. Bacterial-host cell contact triggers the activation of the T3SS and the subsequent insertion of a translocon pore into the target cell membrane, which serves as a conduit for the passage of effector proteins. Therefore the initial interaction between T3SS-bearing bacteria and host cells is the critical step in the deployment of the protein secretion machine, yet this process remains poorly understood. Here, we use high-throughput cryo-electron tomography (cryo-ET) to visualize the T3SS-mediated Salmonella-host cell interface. Our analysis reveals the intact translocon at an unprecedented level of resolution, its deployment in the host cell membrane, and the establishment of an intimate association between the bacteria and the target cells, which is essential for effector translocation. Our studies provide critical data supporting the long postulated direct injection model for effector translocation.
Targeted inhibition of β-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation.

OBJECTIVE Wnt/β-catenin pathway plays a critical role in modulating embryonic development, cell growth, and differentiation. The over-expression of β-catenin activates this pathway and up-regulates expression of matrix metalloproteinase-13 (MMP-13), and promotes matrix degradation and occurrence of osteoarthritis (OA). This study aims to explore the effect of miR-320 expression in OA chondrocyte and underlying mechanisms. PATIENTS AND METHODS Chondrocyte tissues from OA patients and normal individuals were collected for the detection of expression levels of miR-320, β-catenin, MMP-13, and alpha-1 chain of type II collagen (COL2A1). Dual luciferase reporter assay was performed to test targeted regulation between miR-320 and β-catenin. IL-1β was used to simulate in vitro cultured chondrocytes, which were transfected with miR-320 mimic and/or si-β-catenin, followed by quantification of miR-320, β-catenin, MMP-13, and COL2A1. RESULTS In chondrocytes of OA patients, expression of microRNA (miR)-320 is decreased. Bioinformatics analysis revealed complementary binding sites between miR-320 and β-catenin. Compared to control group, increasing levels of β-catenin and MMP-13 expression with reduction of miR-320 and COL2A1 expressions were observed in OA chondrocytes. Transfection of miR-320 mimic and/or si-β-catenin depressed expression of β-catenin and MMP-13 inside chondrocytes, accompanied with elevation of COL2A1 expression. CONCLUSIONS MiR-320 expression in OA chondrocyte is decreased, accompanied with up regulation of β-catenin and MMP-13. MiR-320 can inhibit β-catenin and MMP-13 expressions, elevates COL2A1 expression, which provides novel insights for the treatment of osteoarthritis.
Bedside Ultrasound Versus Chest Radiography for Detection of Pulmonary Edema: A Prospective Cohort Study

Chest radiography has been the preferred imaging study to assess pulmonary congestion. However, chest radiography interpretation is influenced by the level of expertise and high interobserver variability. Lung ultrasound (US) may produce more objective findings through evaluation of vertical comet tail artifacts known as B‐lines, which are created by a decrease in the ratio of alveolar air to fluid pulmonary content. Few studies have directly compared chest radiography to bedside US against a reference standard for the diagnosis of pulmonary edema. This study compared the sensitivity and specificity of bedside US and chest radiography in diagnosing pulmonary edema.
Variations of perceived load and well-being between normal and congested weeks in elite case study handball team

ABSTRACT The aim of this study was two-fold: (i) to analyze the variations in internal load and well-being in professional handball players between normal and congested weeks and (ii) to analyze the variations between training days within weeks. Twenty male players (26.5 ± 4.9 yo) were monitored during a full season. MD-1 (match day −1) revealed larger decreases in muscle soreness (−17.3%, [−26.6;−6.9]) and fatigue (−16.6%, [−24.8;−7.4]) in congested weeks. Regarding MD-2, larger decreases in DOMS (−19.9%, [−30.5;−7.6]), fatigue (−19.7%, [−30.0;−7.9] and the Hooper index (−16.7%, [−25.6;−6.7]) were found in congested weeks. The results of this study reveal that larger variations between normal and congested weeks occurred in MD-2 and MD-3, with greater values of load and lower levels of well-being occurring in normal weeks. Within-weeks changes revealed greater loads occurring on MD-3 and MD-2 in comparison to MD-1; in the opposite way, greater values of muscle soreness and fatigue occurred on MD-1.
To accept or not to accept: Level of moral concern impacts on tolerance of Muslim minority practices

Living with diversity requires that we sometimes accept outgroup practices that we personally disapprove of (i.e., tolerance). Using an experimental design, we examined Dutch majority group members’ tolerance of controversial practices with varying degrees of moral concern, performed by a culturally dissimilar (Muslims) or similar (orthodox Protestant) minority group. Furthermore, we examined whether arguments in favour or against (or a combination of both) the specific practice impacted tolerance. Results indicated that participants expressed less tolerance for provocative practices when it was associated with Muslims than orthodox Protestants, but not when such practices elicit high degrees of moral concern. This indicates that opposition towards specific practices is not just a question of dislike of Muslims, but can involve disapproval of specific practices. Argument framing did not have a consistent effect on the level of tolerance for the practices.
Site specific hypermethylation of CpGs in Connexin genes 30, 26 and 43 in different grades of glioma and attenuated levels of their mRNAs

Abstract Aim: Gliomas, the intracranial tumours are considered the deadliest malignancies. The gap junctional Connexins (Cxs) that maintain cellular homeostasis perform a unique function in glial tumour suppression. However, the differential methylation patterns of Cxs were not revealed in glioma so far. The current study attempts to categorise promoter methylation of Cx30 and Cx26 and intron methylation of Cx43 in different grades of human glioma. Materials and methods: About 85 glioma patients with pathologically confirmed grades and 15 control brain tissues were recruited in the study. Bisulphite-PCR-Single Stranded Conformation analysis(SSCA), Bisulphite sequencing and MeDIP-qPCR were carried out to assess methylation status and Cx mRNA levels were also analysed to evaluate the effect of methylation. Results: We found that promoter CpG islands(CpGs) reside in Sp1 and Ap2 sites of Cx30 and 26 were hypermethylated in high grades (HG) of glioma rather than low grades. The input % of both was significantly increased (p < 0.03) in progressive grades. Interestingly, Cx43 could exhibit a significant increase (p < 0.05) in input % only in grade IV. While, Cx30 and 26 mRNAs were downregulated according to their methylation status in progressive fashion with grades, Cx43 was downregulated irrespective of intron methylation. Conclusion: Thus, we suggest that the sites and extent of methylation of Cxs (30 and 26 but not in 43) are found to be altered. In different grades of glioma can provide better appreciation of the grade of the patient and might help in strategies based on epigenetic approaches.
Reported Consumption of Low-Calorie Sweetener in Foods, Beverages, and Food and Beverage Additions by US Adults: NHANES 2007–2012

Abstract Background Low-calorie sweeteners (LCSs), artificial sweeteners, or high-intensity sweeteners are incorporated into foods, beverages, and food and beverage additions (FBAs). Many prior studies have focused on LCS beverage consumption, but not included LCS consumption from foods or FBAs. Objectives We aimed to describe the prevalence of LCS consumption by US adults, and to examine the relation between intake of products containing LCSs and macronutrients. Methods Two nonconsecutive 24-h dietary recalls from NHANES 2007–2012 and the National Cancer Institute usual intake method were used to estimate prevalence of LCS intake from foods, beverages, and FBAs, and macronutrients among US adults aged ≥19 y (n = 14,098, weighted n = 218,391,752) in a cross-sectional study. The prevalence of LCS consumption from reported foods, beverages, and FBAs among US adults was examined by sociodemographic characteristics and body mass index (BMI). Logistic regression estimated ORs and 95% CIs for associations between sociodemographic characteristics and LCS use (overall and in foods, beverages, and FBAs). Results Among adults, 47.8% reported intake of ≥1 food, beverage, or FBA containing LCSs over 2 d. Intake was higher among: women non-Hispanic whites, college graduates or higher, and those with higher income and obese BMIs (P < 0.001). Intake of beverages containing LCSs was higher for ages 51–70 y than 19–30 y and those with overweight and obese BMIs (P < 0.001) than for normal-weight individuals. Calories, carbohydrate, and sugar intake were lower and fiber was higher in LCS-consumers than in nonconsumers. Specifically, calories from beverages were lower in those who reported LCS intake. Conclusions Individuals reporting LCS consumption demonstrated lower total energy intake than did individuals without LCS intake. Although the main source of LCSs in the US adult diet was beverages (31.9%), we found that FBAs also present a significant contribution (25.2%), surpassing food (9.3%). This enables targeted understanding of national consumption of these products as well as dietary education and intervention opportunities.
Pulmonary Vein Stenosis: Outcomes in Children With Congenital Heart Disease and Prematurity.

Pulmonary vein stenosis (PVS) is a rare condition that has been linked to prematurity and congenital heart disease (CHD). Despite these associations, treatment options are limited and outcomes are guarded. We investigated differences in PVS outcomes based on the presence of CHD and prematurity, and risk factors for mortality or lung transplantation in PVS. Single-center retrospective cohort study of patients diagnosed with PVS between January 2005 and May 2016 and identified by ICD codes with chart validation. Cox proportional hazard models assessed risk factors for the composite outcome of mortality or lung transplantation. Ninety-three patients with PVS were identified: 65 (70%) had significant CHD, 32 (34%) were premature, and 14 (15%) were premature with CHD. Sixty-five (70%) underwent a PVS intervention and 42 (46%) underwent ≥2 interventions. Twenty-five subjects (27%) died or underwent lung transplant 5.8 months (interquartile range [IQR] 1.1, 15.3) after diagnosis. There was no difference in age at diagnosis or mortality based on presence of CHD or prematurity. PVS diagnosis before age 6 months and greater than 1 pulmonary vein affected at diagnosis were associated with higher mortality (hazards ratio [HR] 3.4 (95% confidence interval 1.5, 7.5), P = 0.003, and HR 2.1 per additional vein affected (95% confidence interval 1.3, 3.4), P = 0.004, respectively). Survival in children with PVS is poor, independent of underlying CHD or prematurity. Younger age and greater number of veins affected at diagnosis are risk factors for worse outcome. Understanding causal mechanisms and development of treatment strategies are necessary to improve outcomes.
Racial Disparities and the Effect of County Level Income on the Incidence and Survival of Young Men with Anal Cancer

Abstract Purpose: Prior studies have identified a racial disparity in incidence and survival of squamous cell carcinoma of the anus (SCCA) in the young African American male population. We aim to determine whether racial disparities are independent of income and urban location. Methods: The National Cancer Institute's Surveillance of Epidemiology and End Results database was queried for data on patients with SCCA for the years of 2000–2013. Cox regression was used to determine the effect of race, county median family income, rural–urban continuum, and stage of disease on overall survival. Results: The incidence rate of SCCA was significantly higher in black men <50 years old than in white men. Black race had a hazard ratio of 1.55 (confidence interval [CI] 1.33–1.81) when controlling for age, stage, income, and urban–rural status. Each $10,000 increase in county median family income was protective with a hazard ratio of 0.90 (CI 0.86–0.94). Residence in a metropolitan area did not significantly affect survival. Conclusions: The lower survival of black men <50 years old with SCCA is independent of income, urban location, and stage of disease. Further efforts are needed to target this at-risk population and the authors suggest wide application of previously validated screening programs for anal dysplasia.
Pembrolizumab for the treatment of gastric cancer

ABSTRACT Introduction: Gastric cancer is one of a few gastrointestinal malignancies in which immunotherapy has shown meaningful activity. Pembrolizumab is the first and only immune checkpoint inhibitor to be FDA-approved in gastric cancer. Areas Covered: This review summarizes the current and emerging clinical evidence for immune checkpoint inhibitors in advanced and metastatic gastric cancer, with a focus on pembrolizumab. Expert Commentary: Pembrolizumab has shown impressive activity in the third-line treatment of locally advanced and metastatic gastric cancer. It is currently being studied as upfront therapy in combination with chemotherapy. The emerging understanding of the molecular alterations and tumor immune microenvironment as predictors of immunotherapy response in gastric cancer are discussed. The impact of gastric mucosal dysbiosis on gastric carcinogenesis and the modulation of immunotherapy response by the gut microbiome are also reviewed.
Can Adversarially Robust Learning Leverage Computational Hardness?

Making learners robust to adversarial perturbation at test time (i.e., evasion attacks) or training time (i.e., poisoning attacks) has emerged as a challenging task. It is known that for some natural settings, sublinear perturbations in the training phase or the testing phase can drastically decrease the quality of the predictions. These negative results, however, are information theoretic and only prove the existence of such successful adversarial perturbations. A natural question for these settings is whether or not we can make classifiers computationally robust to polynomial-time attacks. In this work, we prove strong barriers against achieving such envisioned computational robustness both for evasion and poisoning attacks. In particular, we show that if the test instances come from a product distribution (e.g., uniform over $\{0,1\}^n$ or $[0,1]^n$, or isotropic $n$-variate Gaussian) and that there is an initial constant error, then there exists a polynomial-time attack that finds adversarial examples of Hamming distance $O(\sqrt n)$. For poisoning attacks, we prove that for any learning algorithm with sample complexity $m$ and any efficiently computable "predicate" defining some "bad" property $B$ for the produced hypothesis (e.g., failing on a particular test) that happens with an initial constant probability, there exist polynomial-time online poisoning attacks that tamper with $O (\sqrt m)$ many examples, replace them with other correctly labeled examples, and increases the probability of the bad event $B$ to $\approx 1$. Both of our poisoning and evasion attacks are black-box in how they access their corresponding components of the system (i.e., the hypothesis, the concept, and the learning algorithm) and make no further assumptions about the classifier or the learning algorithm producing the classifier.
An investigation into the impact of acute stress on encoding in older adults

ABSTRACT Acute psychological stress commonly occurs in young and older adults’ lives. Though several studies have examined the influence of stress on how young adults learn new information, the present study is the first to directly examine these effects in older adults. Fifty older adults (M age = 71.9) were subjected to either stress induction or a control task before learning two types of information: a short video and a series of pictures. Twenty-four hours later, they were exposed to misleading information about the video and then completed memory tests for the video and pictures. Heart rate and cortisol measures suggest that a physiological stress response was successfully induced. Though pre-encoding stress had little impact on memory accuracy, stress did influence errors of omission on the cued recall test for the video. Findings are discussed in the context of previous research examining the effects of stress on memory in older adults.
Most similar neighbor imputation of forest attributes using metrics derived from combined airborne LIDAR and multispectral sensors

ABSTRACT In the context of predicting forest attributes using a combination of airborne LIDAR and multispectral (MS) sensors, we suggest the inclusion of normalized difference vegetation index (NDVI) metrics along with the more traditional LIDAR height metrics. Here the data fusion method consists of back-projecting LIDAR returns onto original MS images, avoiding co-registration errors. The prediction method is based on non-parametric imputation (the most similar neighbor). Predictor selection and accuracy assessment include hypothesis tests and over-fitting prevention methods. Results show improvements when using combinations of LIDAR and MS compared to using either of them alone. The MS sensor has little explanatory capacity for forest variables dependent on tree height, already well determined from LIDAR alone. However, there is potential for variables dependent on tree diameters and their density. The combination of LIDAR and MS sensors can be very beneficial for predicting variables describing forests structural heterogeneity, which are best described from synergies between LIDAR heights and NDVI dispersion. Results demonstrate the potential of NDVI metrics to increase prediction accuracy of forest attributes. Their inclusion in the predictor dataset may, however, in a few cases be detrimental to accuracy, and therefore we recommend to carefully assess the possible advantages of data fusion on a case-by-case basis.
Comprehensive shotgun lipidomics of human meibomian gland secretions using MS/MSall with successive switching between acquisition polarity modes[S]

The lipid composition of human meibomian gland secretions (meibum) has been analyzed using both targeted and untargeted mass spectrometric approaches, each of which has its advantages and disadvantages. Herein we report the results of shotgun lipidomic profiling of human meibum using a new approach that combines the advantages of targeted and untargeted analyses to yield highly sensitive and comprehensive profiles. Samples containing an estimated 7–13 µg (8–16 nL) of human meibum lipids were analyzed using MS/MSall, an untargeted approach for MS/MS. Using MS/MSall with ESI and successive polarity switching, we obtained tandem mass spectra in both modes at every 1 Da step for all ions in the m/z 200–1,200 range. In approximately 12 min, a total of 2 MS spectra and 2,000 MS/MS spectra were acquired for each sample, from which targeted analysis information was extracted. This approach allowed for the comprehensive and highly sensitive detection of meibum lipids, including species low in abundance. Altogether, more than 600 unique lipid molecular species were identified in meibum, 3 times more than previously reported in untargeted analyses of meibum samples. This untargeted MS and MS/MSall approach may be extended to other biological systems for the detection of lipids with sensitivity comparable to targeted analysis.
Favorable outcomes of prepackaged low‐residue diet on bowel preparation for colonoscopy: Endoscopist‐blinded randomized controlled trial

2 L polyethylene glycol plus an ascorbic acid (PEGA) is known to be as effective. However, 2 L polyethylene glycol‐based regimens are often still difficult for patients to tolerate. Therefore, we conducted this study to evaluate the potential of 1 L PEGA with prepackaged low‐residue diet (PLD) as an alternative to 2 L PEGA before colonoscopy.
Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning

Background: Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. Methods: We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. Results: Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38–1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43–1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55–1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59–1.39). Two sessions of HBO treatment exhibited no advantage over one session. Conclusions: The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.
Berberine Ameliorates High Glucose-Induced Cardiomyocyte Injury via AMPK Signaling Activation to Stimulate Mitochondrial Biogenesis and Restore Autophagic Flux

Background: Type II diabetes (T2D)-induced cardiomyocyte hypertrophy is closely linked to the impairment of mitochondrial function. Berberine has been shown to be a promising effect for hypoglycemia in T2D models. High glucose-induced cardiomyocyte hypertrophy in vitro has been reported. The present study investigated the protective effect and the underlying mechanism of berberine on high glucose-induced H9C2 cell line. Methods: High glucose-induced H9C2 cell line was used to mimic the hyperglycemia resulting in cardiomyocyte hypertrophy. Berberine was used to rescue in this model and explore the mechanism in it. Confocal microscopy, immunofluorescence, RT-PCR, and western blot analysis were performed to evaluate the protective effects of berberine in high glucose-induced H9C2 cell line. Results: Berberine dramatically alleviated hypertrophy of H9C2 cell line and significantly ameliorated mitochondrial function by rectifying the imbalance of fusion and fission in mitochondrial dynamics. Furthermore, berberine further promoted mitogenesis and cleared the damaged mitochondria via mitophagy. In addition, berberine also restored autophagic flux in high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation. Conclusion: Berberine ameliorates high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation to stimulate mitochondrial biogenesis and restore autophagicflux in H9C2 cell line.