Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a Novel Multiplex PCR Panel Compared to Quantitative Bacterial Culture for Diagnosis of Lower Respiratory Tract Infections

Quantitative bacterial culture of bronchoalveolar lavage fluids (BALF) is labor-intensive, and the delay involved in performing culture, definitive identification, and susceptibility testing often results in prolonged use of broad-spectrum antibiotics. The Unyvero lower respiratory tract (LRT) panel (Curetis, Holzgerlingen, Germany) allows the multiplexed rapid detection and identification of 20 potential etiologic agents of pneumonia within 5 h of collection. In addition, the assay includes detection of gene sequences that confer antimicrobial resistance. ABSTRACT Quantitative bacterial culture of bronchoalveolar lavage fluids (BALF) is labor-intensive, and the delay involved in performing culture, definitive identification, and susceptibility testing often results in prolonged use of broad-spectrum antibiotics. The Unyvero lower respiratory tract (LRT) panel (Curetis, Holzgerlingen, Germany) allows the multiplexed rapid detection and identification of 20 potential etiologic agents of pneumonia within 5 h of collection. In addition, the assay includes detection of gene sequences that confer antimicrobial resistance. We retrospectively compared the performance of the molecular panel to routine quantitative bacterial culture methods on remnant BALF. Upon testing 175 BALF, we were able to analyze positive agreement of 181 targets from 129 samples, and 46 samples were negative. The positive percent agreement (PPA) among the microbial targets was 96.5%, and the negative percent agreement (NPA) was 99.6%. The targets with a PPA of <100% were Staphylococcus aureus (34/37 [91.9%]), Streptococcus pneumoniae (10/11 [90.9%]), and Enterobacter cloacae complex (2/4 [50%]). For the analyzable resistance targets, concordance with phenotypic susceptibility testing was 79% (14/18). This study found the Unyvero LRT panel largely concordant with culture results; however, no outcome or clinical impact studies were performed.
Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study

Abstract Objective To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. Design Population based cohort study. Setting The UK Clinical Practice Research Datalink. Participants The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. Main outcome measures Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. Results Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. Conclusions Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. Trial registration ClinicalTrials.gov NCT03948620
Spindle pole bodies function as signal amplifiers in the Mitotic Exit Network

The Mitotic Exit Network (MEN), a budding yeast Ras-like signal transduction cascade, translates nuclear position into a signal to exit from mitosis. Here we describe how scaffolding the MEN onto spindle pole bodies (SPB—centrosome equivalent) allows the MEN to couple the final stages of mitosis to spindle position. Through the quantitative analysis of the localization of MEN components, we determined the relative importance of MEN signaling from the SPB that is delivered into the daughter cell (dSPB) during anaphase and the SPB that remains in the mother cell. Movement of half of the nucleus into the bud during anaphase causes the active form of the MEN GTPase Tem1 to accumulate at the dSPB. In response to Tem1’s activity at the dSPB, the MEN kinase cascade, which functions downstream of Tem1, accumulates at both SPBs. This localization to both SPBs serves an important role in promoting efficient exit from mitosis. Cells that harbor only one SPB delay exit from mitosis. We propose that MEN signaling is initiated by Tem1 at the dSPB and that association of the downstream MEN kinases with both SPBs serves to amplify MEN signaling, enabling the timely exit from mitosis.
Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage.

Glioblastoma multiforme (GBM) is a grade IV astrocytoma, which is the most aggressive form of brain tumor. The standard of care for this disease includes surgery, radiotherapy and temozolomide (TMZ) chemotherapy. Poor accumulation of TMZ at the tumor site, tumor resistance to drug and dose-limiting bone marrow toxicity eventually reduce the success of this treatment. Herein, we have encapsulated > 500 drug molecules of TMZ into the biocompatible protein nanocage, apoferritin (AFt), using a 'nanoreactor' method (AFt-TMZ). AFt is internalized by transferrin receptor 1-mediated endocytosis and is therefore able to facilitate cancer cell-uptake and enhance drug efficacy. Following encapsulation, the protein cage retained its morphological integrity and surface charge, hence its cellular recognition and uptake are not affected by the presence of this cargo. Additional benefits of AFt include maintenance of TMZ stability at pH 5.5 and drug release under acidic pH conditions, encountered in lysosomal compartments. MTT assays revealed that the encapsulated agents displayed significantly increased anti-tumor activity in U373V (vector control) and, remarkably the isogenic, U373M (MGMT expressing TMZ-resistant) GBM cell lines, with GI50 values < 1.5 μM for AFt-TMZ, compared to 35 μM and 376 µM for unencapsulated TMZ against U373V and U373M, respectively. The enhanced potency of AFt-TMZ was further substantiated by clonogenic assays. Potentiated G2/M cell cycle arrest following exposure of cells to AFt-TMZ indicated an enhanced DNA damage burden. Indeed, increased O6-methylguanine (O6-MeG) adducts in cells exposed to AFt-TMZ and subsequent generation of γH2AX foci, support the hypothesis that AFt significantly enhances the delivery of TMZ to cancer cells in vitro; overwhelming the direct O6-MeG repair conferred by MGMT. We have additionally encapsulated > 500 molecules of the N3-propargyl imidazotetrazine analog (N3P), developed to combat TMZ resistance, and demonstrated significantly enhanced activity of AFt-N3P against GBM and colorectal carcinoma cell lines. These studies support the use of AFt as a promising nano-delivery system for targeted delivery, lysosomal drug release and enhanced imidazotetrazine potency for treatment of GBM and wider-spectrum malignancies.
DIŞARDAN YEMEK HİZMETİ ALINAN BİR EĞİTİM VE ARAŞTIRMA HASTANESİNDE PERSONELİN YEMEK HİZMETLERİNİN DEĞERLENDİRİLMESİ

One of the common services provided by hospitals is food services. Food services and personnel services, as well as contributing to the process of treatment are the nature of medical services. The purpose of this survey is to determine the ideas and assessments of hospital staff about outsourced food services. Data related to the evaluation and opinions of hospital personnel on the food services were obtained by using “Food Evaluation Questionnaire”. This questionnaire includes 28 items. SPSS 15.0 statistical software was used to analyze the data. Subjective evaluation differences between personnel groups with respect to their characteristics including age, sex, title etc. were tested by chi-square tests. The relationship between variables were calculated and analyzed by the correlation analysis. In this survey, it was found that 83% of the personnel thought the dining hall is insufficient, 69% of whom had complaints about inconvenient placement of tables and chairs, 63% dissatisfied with waiting more than 5 minutes in the queue, 42% provided the food by other sources, 53% were not satisfied with the way of service delivery, 57% claimed the dishes are not suitable for a balanced diet, 60% is not happy with consistence of meals, 83% had complaints about crowd and noise of dining hall, 71% had complaints related to food preparation and taste, and 59% of personnel did not consume all given dishes. However, 81% of the staff said the attitude of food staff is fine while serving as medium and good; whereas 63% said the amount of food served is sufficient. 69% rated bread good quality and 85% evaluated the service style hygienically appropriate. In this survey, it was found that hospital personnel are greatly dissatisfied with food services provided for them. Considering characteristics of the personnel in terms of age, sex, educational status, marital status; there are statistical differences between their reviews and evaluations related to the food services. According to
Strength and Endurance Training in Older Women in Relation to ACTN3 R577X and ACE I/D Polymorphisms

The purpose of this study is to analyze the effect of two genetic polymorphisms, ACTN3 R577X, and ACE I/D, on physical condition in a sample of active older women after a two-year training period. The sample was composed of 300 healthy women over the age of 60 who underwent a two-year training program. Adapted tests from the Senior Fitness Test were used. The genotyping of the polymorphisms was obtained from the participants’ DNA via buccal swabs. The analysis of the ACE polymorphism did not reveal differences between genotypes. The analysis of the R577X polymorphism showed a favorable effect for the ACTN3 XX genotype in tests for leg strength (p: 0.001) after training, compared to the other genotypes, and also in the analysis of the combined effect of the polymorphism (ACE II + ACTN3 RX/XX). The intragroup effect revealed an improvement in arm strength for carriers of the X allele after 24 months of training (p < 0.05). The endurance values significantly worsened in all study groups. Conclusions: The R577X polymorphism of ACTN3 may have an important role in capacities related to muscle strength, providing a beneficial effect for carriers of the X allele.
p53’s Extended Reach: The Mutant p53 Secretome

p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding TP53 gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome. In this review, we discuss how the loss or dominant-negative inhibition of wild-type p53 in concert with a gain of neomorphic properties observed for many mutant p53 proteins, shapes a tumor cell secretome that creates a supportive microenvironment at the primary tumor site and primes niches in distant organs for future metastatic colonization.
Delayed correlations improve the reconstruction of the brain connectome

The brain works as a large-scale complex network, known as the connectome. The strength of the connections between two brain regions in the connectome is commonly estimated by calculating the correlations between their patterns of activation. This approach relies on the assumption that the activation of connected regions occurs together and at the same time. However, there are delays between the activation of connected regions due to excitatory and inhibitory connections. Here, we propose a method to harvest this additional information and reconstruct the structural brain connectome using delayed correlations. This delayed-correlation method correctly identifies 70% to 80% of connections of simulated brain networks, compared to only 5% to 25% of connections detected by the standard methods; this result is robust against changes in the network parameters (small-worldness, excitatory vs. inhibitory connection ratio, weight distribution) and network activation dynamics. The delayed-correlation method predicts more accurately both the global network properties (characteristic path length, global efficiency, clustering coefficient, transitivity) and the nodal network properties (nodal degree, nodal clustering, nodal global efficiency), particularly at lower network densities. We obtain similar results in networks derived from animal and human data. These results suggest that the use of delayed correlations improves the reconstruction of the structural brain connectome and open new possibilities for the analysis of the brain connectome, as well as for other types of networks.
Enamel thickness and growth rates in modern human permanent first molars over a 2000 year period in Britain.

OBJECTIVES This study explores variation and trends in first molar enamel thickness and daily enamel secretion rates over a 2000 year period in Britain. METHODS Permanent first molars (n = 89) from the Roman, Anglo-Saxon, and Medieval periods, as well as modern-day Britain, were analyzed using standard histological methods. Relative enamel thickness (RET) and linear measurements of cuspal and lateral thickness were calculated for mesial cusps. Daily secretion rates (DSRs) were calculated for inner, mid, and outer enamel regions in both cuspal and lateral enamel. Significant differences and trends were identified between samples using nonparametric statistical tests. RESULTS Enamel thickness differed between some populations, but no temporal trends were identified. Early Anglo-Saxon molars had significantly thinner RET than both Late Anglo-Saxon (p < .00) and Medieval (p < .00) molars. Lateral enamel from the Roman molars was significantly thinner than the modern-day sample (p = .04). In contrast, a significant slowing trend in DSRs was observed across the more ancient to modern-day samples in every measured region except the mid-lateral enamel region. DISCUSSION This study presents the first evidence for a gradual slowing in the daily rate that enamel is secreted in molars over the past 2000 years in Britain. However, this trend was not matched by consistent or significant positive or negative shifts in enamel thickness. These findings suggest that modern human molars of similar enamel thickness, from different modern and ancient populations, formed at different rates.
Characterization and pro-inflammatory potential of indoor mold particles.

A number of epidemiological studies find an association between indoor air dampness and respiratory health effects. This is often suggested to be linked to enhanced mold growth. However, the role of mold are obviously difficult to disentangle from other dampness related exposure including microbes as well as non-biological particles and chemical pollutants. The association may partly be due to visible mycelial growth and a characteristic musty smell of mold. Thus, the potential role of mold exposure should be further explored by evaluating information from experimental studies elucidating possible mechanistic links. Such studies show that exposure to spores and hyphal fragments may act as allergens and pro-inflammatory mediators, and that they may damage airways by the production of toxins, enzymes and volatile organic compounds. In the present review, we hypothesizes that continuous exposure to mold particles may result in chronic low-grade pro-inflammatory responses contributing to respiratory diseases. We summarize some of the main methods for detection and characterization of fungal aerosols and highlight in vitro research elucidating how molds may induce toxicity and pro-inflammatory reactions in human cell models relevant for airway exposure. Data suggest that the fraction of fungal hyphal fragments in indoor air is much higher than that of airborne spores, and the hyphal fragments often have a higher pro-inflammatory potential. Thus, hyphal fragments of prevalent mold species with strong pro-inflammatory potential may be particularly relevant candidates for respiratory diseases associated with damp/mold-contaminated indoor air. Future studies linking of indoor air dampness with health effects should assess the toxicity and pro-inflammatory potential of indoor air particulate matter, and combined this information with a better characterization of biological components including hyphal fragments from both pathogenic and non-pathogenic mold species. Such studies may increase our understanding of the potential role of mold exposure.
Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.
Cannabidiol protects against high glucose‐induced oxidative stress and cytotoxicity in cardiac voltage‐gated sodium channels

Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetes‐associated arrhythmias are unclear. We hypothesized that high glucose could adversely affect Nav1.5, the major cardiac sodium channel isoform of the heart, at least partially via oxidative stress. We further hypothesized that cannabidiol (CBD), one of the main constituents of Cannabis sativa, through its effects on Nav1.5, could protect against high glucose‐elicited oxidative stress and cytotoxicity.
The Role of Th17-Related Cytokines in Atopic Dermatitis

T helper-17 (Th17) cells, which mainly produce IL-17, are associated with development of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and psoriasis. IL-17 and related cytokines are therapeutic targets of these diseases. In atopic dermatitis (AD), Th2 cytokines such as IL-4 and IL-13 are regarded to be the main player of the disease; however, Th17 cytokines are also expressed in AD skin lesions. Expression of IL-22 rather than IL-17 is predominant in AD skin, which is contrary to cytokine expression in psoriasis skin. Relatively low IL-17 expression in AD skin can induce relatively low antimicrobial peptide expression, which may be a reason why bacterial infection is frequently seen in AD patients. Failure of clinical trials for investigating the efficacy of anti-IL-12/23 p40 in AD has suggested that IL-17 expressed in skin lesions should not be the main player but a bystander responding to barrier dysfunction.
Association between dietary protein intake and the risk of depressive symptoms in adults.

Depression is an important public health problem. The aim of the study is to explore the associations of total protein intake and protein sources with the risk of depressive symptoms. This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2007-2014. Dietary protein intake was obtained from two 24-hour dietary recall interviews. Depressive symptoms were assessed by a nine-item Patient Health Questionnaire (PHQ-9). Logistic regression models and restricted cubic spline models were used to estimate the associations of total protein intake (g/kg·d), protein sources with the risk of depressive symptoms. A total of 17 845 individuals aged 18 and older were included in this study. Total protein intake was inversely associated with the risk of depressive symptoms. The full-adjusted odd ratio (OR) with 95% confidence interval (CI) of depressive symptoms was 0.34 (0.17-0.68) for quartile (Q) 4 versus Q1 of total protein intake. For protein intake from milk and milk products, the association with depressive symptoms was significant both for Q2 versus Q1 (OR: 0.61; 95% CI: 0.41-0.93) and Q3 versus Q1 (OR: 0.37; 95% CI: 0.24-0.59) in full-adjusted model. In the dose-response analysis, the shape of the associations of total protein intake and protein intake from milk and milk products with the risk of depressive symptoms was approximatively L-shaped and U-shaped, respectively. The present study demonstrated that total protein intake and protein intake from milk and milk products might reduce the risk of depressive symptoms in US adults.