Miracle-dz/UniFAR-FTUs huggingface dataset:
Diastolic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Case Controlled Studies

Background: Chronic obstructive pulmonary disease (COPD) and left ventricular diastolic dysfunction (LVDD) are major causes of morbidity and mortality and have overlapping symptomatology including cough and dyspnea. Whether COPD is a risk factor for LVDD remains largely unclear. The objective of this meta-analysis was to determine if the prevalence of the LVDD as determined by echocardiographic parameters is increased in COPD patients. Methods: We used a time-and-language-restricted search strategy resulting in identification of 4,912 studies of which 15 studies met our apriori inclusion criteria; 4,897 were excluded, such duplicates, foreign language articles were excluded. We performed a meta-analysis of standard echo parameters on the fifteen case control studies related to diastolic dysfunction. The meta-analysis was performed using Review Manager, version 5.3 (Cochrane Collaboration). Results: A total of 15 studies with 1,403 subjects were included. There were no differences in left ventricular ejection fraction between COPD and non-COPD population. Patients with COPD had prolonged isovolumetric relaxation time (IVRT) (mean difference 20.84 [95% CI 12.21, 29.47]; P< 0.00001), lower E/A ratio (mean difference - 0.24 [95% CI −0.34, 00.14]; P < 0.00001), higher transmitral A wave peak velocity (Apv) (mean difference 11.71 [95% CI 4.80, 18.62]; P< 0.00001), higher E/e’ ratio (mean difference 1.88 [95% CI 1.23, 2.53]; P< 0.00001), lower mitral E wave peak velocity (Epv) (mean difference −8.74 [95% CI −13.63, −3.85]; P< 0.0005), prolonged deceleration time (DT) (mean difference 50.24 [95% CI 15.60, 84,89]; P< 0.004), a higher right ventricular end diastolic diameter (RVEDD) (mean difference 8.02 [95% CI 3.45, 12.60]; P< 0.0006) compared to controls. COPD patients had a higher pulmonary arterial pressure (mean difference 10.52 [95% CI 3.98, 17.05]; P< 0.002). Differences in septal e’ velocity (mean difference −2.69 [95% CI −6.07, 0.69]; P< 0.12) and in lateral e’ velocity (mean difference −2.84 [95% CI 5.91, 0.24]; P< 0.07) trended towards significance but did not meet our cutoff for statistical significance (p < 0.05). Conclusions: Patients with COPD are more likely to have LVDD as established by echocardiographic parameters. Our findings are likely explainable, in part, by factors such as lung hyperinflation, chronic hypoxia, hypercapnia, systemic inflammation, increased arterial stiffness, subendocardial ischemia, as well as ventricular interdependence; all of which might contribute to the pathogenesis of diastolic dysfunction. Further research is needed to elucidate the pathophysiologic mechanisms of increased LVDD in the COPD population with the potential impact on developing effective therapeutic interventions for these serious disorders.
The effect of immunonutrition on bacterial translocation after Pringle maneuverer in rats

Introduction Temporary clamping of the hepatoduodenal ligament (the Pringle manoeuvre) is the most commonly used method to prevent intraoperative blood loss in liver surgery. Some side effects of the Pringle manoeuvre (PM) can occur. Aim To investigate the effectiveness of preoperative immunonutritional support to prevent bacterial translocation (BT) in rats due to PM. Material and methods Forty Wistar albino rats were randomly divided into four groups. Groups 1 and 2 were fed with normal rat diet and water, and groups 3 and 4 were fed with enteral immunonutrition (Impact Glutamine) containing 1 g/kg/day amino acid in the preoperative period. Group 1 (n = 10) and 4 (n = 10) rats were treated only with laparotomy; group 2 (n = 10) and 3 (n = 10) rats were treated with PM for 30 min with laparotomy. After 30 min, relaparotomy was applied to all groups and portal blood, mesentery, spleen samples were taken for culture purposes. Results Proliferation in portal blood cultures was significantly higher in the samples from the normally fed group (group 2) in whom PM was applied, compared to the other groups (p < 0.001). No proliferation was observed in the PM-treated group (group 3), who also received preoperative immunonutritional support. Conclusions Preoperative immunonutritional support is effective in the prevention of BT due to PM in rats.
Occupational exposures and asthma–COPD overlap in a clinical cohort of adult-onset asthma

Asthma–COPD overlap (ACO) has recently been recognised as a separate phenotype of obstructive airway diseases and is included in several guidelines of asthma and COPD [1–5]. ACO patients have previously been shown to have lower diffusing capacity of the lung, higher blood neutrophil counts and higher interleukin-6 levels compared with asthma patients [6]. In COPD, fixed airway obstruction is considered to develop in response to chronic exposure to noxious inhaled particles [7]. In western countries, the most common cause of COPD is tobacco smoking, but occupational exposure to dusts and fumes has also been shown to increase the risk for developing COPD [7, 8]. However, the role of occupational exposures in the development of ACO is not known. Occupational exposure to vapours, gases, dusts or fumes (VGDF) increases the prevalence of asthma–COPD overlap (ACO) in adult-onset asthma. VGDF exposure is independently associated with ACO and an additive effect with smoking is proposed. http://bit.ly/2LiMiXW
Using intervention mapping approach to finding socio-cognitive determinants of diabetes preventive behaviors

Summary Introduction Diabetes is one of the most common chronic illnesses with complications. The objective of this study was to determine socio-cognitive determinants of diabetes preventive behaviors among sample of at risk group based on intervention mapping approach (IM) in Kermanshah, the west of Iran. Methods This cross-sectional study conducted among a total of 200 male and female aged more than 30 years old referred to health centers that randomly selected to participate voluntarily, during 2018. Participants filled out a self-report questionnaire. Data were analyzed by SPSS version 16 using bivariate correlations and linear regression at 95% significant level. Results The mean age of respondents was 38.4 years [95% CI: 37.3, 39.4], ranged from 30 to 56 years. Socio-cognitive determinants were accounted for 40% of the variation in diabetes prevention behaviors F = 35.559, P < 0.001. As well as, perceived self-efficacy, perceived severity, and perceived barrier were the most influential predictors on diabetes preventive behaviors. Conclusions It seems that planning health promotion programs to reduce barrier to perform diabetes preventive behaviors and increase confidence towards ability to perform preventive behaviors, and seriousness about sides effect of diabetes may be usefulness of the results in order to promotion of diabetes preventive behaviors among at risk group.
Tuberculosis Cutis Orificialis

A 24-year-old female was referred to the department of plastic surgery with a large, painful, fungating lesion of the upper lip that had gradually enlarged over the preceding 9 months (Figure 1). She reported a 9-month history of chronic cough, together with night sweats and significant weight loss, which she quantified by a drop in 2 clothes sizes. She had no medical history and no recent travel history. Physical examination was notable for temporal wasting and bilateral cervical lymphadenopathy. Right upper lobe crackles were heard upon auscultation of her chest. A chest x-ray confirmed the presence of a right upper lobe reticulo-nodular infiltrate, and a complete blood count revealed a normocytic anemia (haemoglobin 10.6 g/dL). Liver and renal function were within normal limits. A test for HIV was negative. A sputum sample sent for Xpert MTB/RIF assay was positive for Mycobacterium tuberculosis nucleic acid without identification of resistance to rifampicin. Mycobacterium tuberculosis was also cultured from sputum after 14 days using Mycobacteria Growth Indicator Tube (MGIT) liquid culture. The GenoType MTBDRplus assay was used for speciation and to genotypically assess for resistance mutations to rifampicin and isoniazid, of which none were identified. Two tissue biopsy specimens obtained from the upper lip lesion demonstrated a dense subepithelial inflammatory cell infiltrate and granulomatous inflammation with no features of dysplasia or invasive malignancy. No viral cytopathic changes were noted. Grocott, Alcian blue, and Periodic-acid Schiff stains failed to identify fungal elements. A Ziehl-Neelsen stain highlighted the presence of acid-fast bacilli. Fine needle aspiration of the enlarged cervical lymph nodes demonstrated granulomatous inflammation in keeping with mycobacterial infection. A diagnosis of pulmonary and cutaneous mycobacterium tuberculosis (specifically, tuberculosis cutis orificialis) was made based on sputum and histopathology results. Cutaneous tuberculosis is uncommon and occurs in 1%–2% of all cases of tuberculosis [1]. Clinical presentations vary widely and are dependent on the mode by which the disease is spread, whether hematogenous, contiguous, or by direct inoculation (Table 1) [1]. Additionally, pauci-bacillary cutaneous hypersensitivity applyparastyle “fig//caption/p[1]” parastyle “FigCapt”
A Surface-Enhanced Raman Spectral Library of Important Drugs Associated With Point-of-Care and Field Applications

During the past decade, the ability of surface-enhanced Raman spectroscopy (SERS) to measure extremely low concentrations, such as mg/L and below, and the availability of hand-held Raman spectrometers, has led to a significant growth in the number and variety of applications of SERS to real-world problems. Most of these applications involve the measurement of drugs, such as quantifying medication in patients, identifying illicit drugs in impaired drivers, and more recently, identifying drugs used as weapons. Similar to Raman spectroscopy, most of the point-of-care and field applications involve the identification of the drug to determine the course of action. However, unlike Raman spectroscopy, spectral libraries are not readily available to perform the necessary identification. In a large part, this is due to the uniqueness of the commercially available SERS substrates, each of which can produce different spectra for the same drug. In an effort to overcome this limitation, we have measured numerous drugs using the most common, and readily available SERS material and hand-held Raman analyzers, specifically gold colloids and analyzers using 785 nm laser excitation. Here we present the spectra of some 39 drugs of current interest, such as buprenorphine, delta-9 tetrahydrocannabinol, and fentanyl, which we hope will aid in the development of current and future SERS drug analysis applications.
Early Root Transcriptomic Changes in Wheat Seedlings Colonized by Trichoderma harzianum Under Different Inorganic Nitrogen Supplies

Wheat is one of the most important crops worldwide. The use of plant growth promoting microorganisms, such as those of the genus Trichoderma, constitutes an alternative to chemical fertilizers, since they are cheaper and are not detrimental to the environment. However, the interaction between Trichoderma and wheat plants has been scarcely studied, at least at a molecular level. In the present work, a microarray approach was used to study the early transcriptomic changes induced in wheat roots by Trichoderma harzianum, applied alone or in combination with different concentrations of calcium nitrate [Ca(NO3)2], which was last used as nitrogen (N) source. Our results show that T. harzianum causes larger transcriptomic changes than Ca(NO3)2 in wheat roots, and such changes are different when plants are challenged with Trichoderma alone or treated with a combination of T. harzianum and Ca(NO3)2. Overall, T. harzianum activates the expression of defense-related genes at early stages of the interaction with the roots, while this fungus reduces the expression of genes related to plant growth and development. Moreover, the current study in wheat roots, subjected to the different T. harzianum and Ca(NO3)2 combinations, reveals that the number of transcriptomic changes was higher when compared against those caused by the different Ca(NO3)2 concentrations than when it was compared against those caused by T. harzianum. N metabolism gene expression changes were in agreement with the levels of nitrate reductase activity measured in plants from Trichoderma plus Ca(NO3)2 conditions. Results were also concordant with plant phenotypes, which showed reduced growth at early interaction stages when inoculated with T. harzianum or with its combination with Ca(NO3)2 at the lowest dosage. These results were in a good agreement with the recognized role of Trichoderma as an inducer of plant defense.
Bordeaux 2018: Wine, Cheese, and γδ T Cells

The first ‘International γδ T cell conference’ took place in Denver, CO (USA) in 2004. Since then, a new meeting is held every two years. During each conference, all participants voted to choose between candidate bids for where to hold the next conference. At the conference held in London in 2016, a majority opted for the bid from a team proposing the 2018 event be held in Bordeaux, France – which is where we therefore gathered on 7-10th of June 2018. The meeting was an undisputed success and it gave us the opportunity to take stock of the increasing basic knowledge about γδ T cells as well as the rapidly expanding interest and activities developing using γδ T cells towards clinical applications. If we were to point to one single ‘take home lesson’; we could say that this conference underlined the impression that the γδ T cell compartment comprises functionally diverse subsets that can occupy niches contributing to either innate or adaptive immunity, and potentially the interface between the two.
Multifactorial Regulation of Myometrial Contractility During Pregnancy and Parturition

The steroid hormones progesterone (P4) and estradiol-17β (E2), produced by the placenta in humans and the ovaries in rodents, serve crucial roles in the maintenance of pregnancy, and the initiation of parturition. Because of their critical importance for species survival, the mechanisms whereby P4 and its nuclear receptor (PR) maintain myometrial quiescence during pregnancy, and for the decline in P4/PR and increase in E2/estrogen receptor (ER) function leading to parturition, are multifaceted, cooperative, and redundant. These actions of P4/PR include: (1) PR interaction with proinflammatory transcription factors, nuclear factor κB (NF-κB), and activating protein 1 (AP-1) bound to promoters of proinflammatory and contractile/contraction-associated protein (CAP) genes and recruitment of corepressors to inhibit NF-κB and AP-1 activation of gene expression; (2) upregulation of inhibitors of proinflammatory transcription factor activation (IκBα, MKP-1); (3) induction of transcriptional repressors of CAP genes (e.g., ZEB1). In rodents and most other mammals, circulating maternal P4 levels remain elevated throughout most of pregnancy and decline precipitously near term. By contrast, in humans, circulating P4 levels and myometrial PR levels remain elevated throughout pregnancy and into labor. However, even in rodents, wherein P4 levels decline near term, P4 levels remain higher than the Kd for PR binding. Thus, parturition is initiated in all species by a series of molecular events that antagonize the P4/PR maintenance of uterine quiescence. These events include: direct interaction of inflammatory transcription factors (e.g., NF-κB, AP-1) with PR; increased expression of P4 metabolizing enzymes; increased expression of truncated/inhibitory PR isoforms; altered expression of PR coactivators and corepressors. This article will review various mechanisms whereby P4 acting through PR isoforms maintains myometrial quiescence during pregnancy as well as those that underlie the decline in PR function leading to labor. The roles of P4- and E2-regulated miRNAs in the regulation and integration of these mechanisms will also be considered.
Using Virtual Reality Exposure Therapy to Enhance Treatment of Anxiety Disorders: Identifying Areas of Clinical Adoption and Potential Obstacles

Despite strong evidence of effectiveness, exposure therapy is an underutilized treatment for anxiety disorders at a time when effective treatment for anxiety is greatly needed. The significant worldwide prevalence and negative impact of anxiety are documented and highlight the importance of increasing therapist and patient use of effective treatment. Obstacles to the use of exposure therapy are explored and steps to lessen these obstacles are proposed. In particular, virtual reality (VR) technology is discussed as a way to increase the availability of exposure therapy. Incorporating VR in therapy can increase the ease, acceptability, and effectiveness of treatment for anxiety. VR exposure therapy (VRET) permits individualized, gradual, controlled, immersive exposure that is easy for therapists to implement and often more acceptable to patients than in vivo or imaginal exposure. VR is presented as a scalable tool that can augment access to and effectiveness of exposure therapy thus improving treatment of anxiety disorders. VR also has the potential to help with assessment and with therapist training standardization. The authors advocate for providing continuing education in VRET to practicing clinicians and including training in exposure therapy and VRET in training programs. Ongoing development of VR applications for clinical use is encouraged, especially when developed in collaboration with software developers, clinical users, therapists who are experienced in VRET, and researchers.
Selective Histone Deacetylase 6 Inhibition Normalizes B Cell Activation and Germinal Center Formation in a Model of Systemic Lupus Erythematosus

Autoantibody production by plasma cells (PCs) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The molecular pathways by which B cells become pathogenic PC secreting autoantibodies in SLE are incompletely characterized. Histone deactylase 6 (HDAC6) is a unique cytoplasmic HDAC that modifies the interaction of a number of tubulin- associated proteins; inhibition of HDAC6 has been shown to be beneficial in murine models of SLE, but the downstream pathways accounting for the therapeutic benefit have not been clearly delineated. In the current study, we sought to determine whether selective HDAC6 inhibition would abrogate abnormal B cell activation in SLE. We treated NZB/W lupus mice with the selective HDAC6 inhibitor, ACY-738, for 4 weeks beginning at 20 weeks-of age. After only 4 weeks of treatment, manifestation of lupus nephritis (LN) were greatly reduced in these animals. We then used RNAseq to determine the genomic signatures of splenocytes from treated and untreated mice and applied computational cellular and pathway analysis to reveal multiple signaling events associated with B cell activation and differentiation in SLE that were modulated by HDAC6 inhibition. PC development was abrogated and germinal center (GC) formation was greatly reduced. When the HDAC6 inhibitor-treated lupus mouse gene signatures were compared to human lupus patient gene signatures, the results showed numerous immune, and inflammatory pathways increased in active human lupus were significantly decreased in the HDAC6 inhibitor treated animals. Pathway analysis suggested alterations in cellular metabolism might contribute to the normalization of lupus mouse spleen genomic signatures, and this was confirmed by direct measurement of the impact of the HDAC6 inhibitor on metabolic activities of murine spleen cells. Taken together, these studies show HDAC6 inhibition decreases B cell activation signaling pathways and reduces PC differentiation in SLE and suggest that a critical event might be modulation of cellular metabolism.
Paclitaxel Response Can Be Predicted With Interpretable Multi-Variate Classifiers Exploiting DNA-Methylation and miRNA Data

To address the problem of resistance to paclitaxel treatment, we have investigated to which extent is possible to predict Breast Cancer (BC) patient response to this drug. We carried out a large-scale tumor-based prediction analysis using data from the US National Cancer Institute’s Genomic Data Commons. These data sets comprise the responses of BC patients to paclitaxel along with six molecular profiles of their tumors. We assessed 10 Machine Learning (ML) algorithms on each of these profiles and evaluated the resulting 60 classifiers on the same BC patients. DNA methylation and miRNA profiles were the most informative overall. In combination with these two profiles, ML algorithms selecting the smallest subset of molecular features generated the most predictive classifiers: a complexity-optimized XGBoost classifier based on CpG island methylation extracted a subset of molecular factors relevant to predict paclitaxel response (AUC = 0.74). A CpG site methylation-based Decision Tree (DT) combining only 2 of the 22,941 considered CpG sites (AUC = 0.89) and a miRNA expression-based DT employing just 4 of the 337 analyzed mature miRNAs (AUC = 0.72) reveal the molecular types associated to paclitaxel-sensitive and resistant BC tumors. A literature review shows that features selected by these three classifiers have been individually linked to the cytotoxic-drug sensitivities and prognosis of BC patients. Our work leads to several molecular signatures, unearthed from methylome and miRNome, able to anticipate to some extent which BC tumors respond or not to paclitaxel. These results may provide insights to optimize paclitaxel-therapies in clinical practice.
The Regulation of Ruminal Short-Chain Fatty Acids on the Functions of Rumen Barriers

The rumen barriers, constituted by the microbial, physical and immune barrier, prevent the transmission of pathogens and toxins to the host tissue in the maintenance of host-microbe homeostasis. Ruminal short-chain fatty acids (SCFAs), which are the important signaling molecules derived from the rumen microbiota, regulate a variety of physiological functions of the rumen. So far, how the ruminal SCFAs regulate the function of rumen barriers is unclear. By the combined methods of transcriptome sequencing, 16S rRNA gene sequencing, and metagenome shotgun sequencing, we have investigated the regulatory effects of ruminal SCFAs on the functions of rumen barriers, by determining the composition and functions of epimural microbiota and on the structure and immunity of the rumen epithelium in goats receiving a 10% (LC group), 35% (MC group), or 65% concentrate diet (HC group). We found that, when the dietary concentrate shifted from 10 to 35%, the increase of total SCFA is associated with the diversification of epimural microbiota and the diversity of its gene pool. Within the microbial community, the relative abundance of genera Sphingobium, Acinetobacter, and Streptococcus increase mostly. Meantime, the signals on pathways concerning the mechanical connections and growth homeostasis in the rumen epithelium were upregulated. Under these conditions, the responses of immune components in the rumen epithelium decrease. However, when the dietary concentrate shifted from 35 to 65%, the increase of acetate and reduction of pH decrease the diversity of epimural microbiota and the diversity of its gene pool. Within the microbial community, the relative abundance of genera Sphingobium, Acinetobacter, and Streptococcus significantly decrease. Concomitantly, the signals on pathways concerning the cell growth and tight junction disruption were upregulated, while the signals on pathways concerning paracellular permeability were downregulated. Under these conditions, the signals on the pathways relating to the immune components increase. Our data thus indicates that diet-SCFA axis maintains the host-microbe homeostasis via promoting the diversification of epimural microbiota and maintaining the integrity of rumen epithelium in healthy animals, while via enhancing the activities of immune barrier in animal with lower rumen pH.