Miracle-dz/UniFAR-FTUs huggingface dataset:
5-Arylideneimidazolones with Amine at Position 3 as Potential Antibiotic Adjuvants against Multidrug Resistant Bacteria

Searching for new chemosensitizers of bacterial multidrug resistance (MDR), chemical modifications of (Z)-5-(4-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-3H-imidazol-4(5H)-one (6) were performed. New compounds (7–17), with fused aromatic rings at position 5, were designed and synthesized. Crystallographic X-ray analysis proved that the final compounds (7–17) were substituted with tertiary amine-propyl moiety at position 3 and primary amine group at 2 due to intramolecular Dimroth rearrangement. New compounds were evaluated on their antibiotic adjuvant properties in either Gram-positive or Gram-negative bacteria. Efflux pump inhibitor (EPI) properties towards the AcrAB-TolC pump in Enterobacter aerogenes (EA289) were investigated in the real-time efflux (RTE) assay. Docking and molecular dynamics were applied to estimate an interaction of compounds 6–17 with penicillin binding protein (PBP2a). In vitro ADME-Tox properties were evaluated for compound 9. Most of the tested compounds reduced significantly (4-32-fold) oxacillin MIC in highly resistant MRSA HEMSA 5 strain. The anthracene-morpholine derivative (16) was the most potent (32-fold reduction). The tested compounds displayed significant EPI properties during RTE assay (37–97%). The naphthyl-methylpiperazine derivative 9 showed the most potent “dual action” of both oxacillin adjuvant (MRSA) and EPI (E. aerogenes). Molecular modeling results suggested the allosteric mechanism of action of the imidazolones, which improved binding of oxacillin in the PBP2a active site in MRSA.
The nature of the progression of drought stress drives differential metabolomic responses in Populus deltoides.

Background and Aims The use of woody crops for Quad-level (approx. 1 × 1018 J) energy production will require marginal agricultural lands that experience recurrent periods of water stress. Populus species have the capacity to increase dehydration tolerance by lowering osmotic potential via osmotic adjustment. The aim of this study was to investigate how the inherent genetic potential of a Populus clone to respond to drought interacts with the nature of the drought to determine the degree of biochemical response. Methods A greenhouse drought stress study was conducted on Populus deltoides 'WV94' and the resulting metabolite profiles of leaves were determined by gas chromatography-mass spectrometry following trimethylsilylation for plants subjected to cyclic mild (-0.5 MPa pre-dawn leaf water potential) drought vs. cyclic severe (-1.26 MPa) drought in contrast to well-watered controls (-0.1 MPa) after two or four drought cycles, and in contrast to plants subjected to acute drought, where plants were desiccated for up to 8 d. Key Results The nature of drought (cyclic vs. acute), frequency of drought (number of cycles) and the severity of drought (mild vs. severe) all dictated the degree of osmotic adjustment and the nature of the organic solutes that accumulated. Whereas cyclic drought induced the largest responses in primary metabolism (soluble sugars, organic acids and amino acids), acute onset of prolonged drought induced the greatest osmotic adjustment and largest responses in secondary metabolism, especially populosides (hydroxycinnamic acid conjugates of salicin). Conclusions The differential adaptive metabolite responses in cyclic vs. acute drought suggest that stress acclimation occurs via primary metabolism in response to cyclic drought, whereas expanded metabolic plasticity occurs via secondary metabolism following severe, acute drought. The shift in carbon partitioning to aromatic metabolism with the production of a diverse suite of higher order salicylates lowers osmotic potential and increases the probability of post-stress recovery.
Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis

Kidney injury due to focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing end-stage renal disease. Homozygous mutations in either glomerular basement membrane or slit diaphragm genes cause early renal failure. Heterozygous carriers develop renal symptoms late, if at all. In contrast to mutations in slit diaphragm genes, hetero- or hemizygous mutations in the X-chromosomal COL4A5 Alport gene have not yet been recognized as a major cause of kidney injury by FSGS. We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls. The results of our case series study suggest a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS. Our results demonstrate that the molecular genetics of different players in the glomerular filtration barrier can be used to evaluate causes of kidney injury. Given the high frequency of X-chromosomal carriers of Alport genes, the analysis of genes involved in the organization of podocyte architecture, the glomerular basement membrane, and the slit diaphragm will further improve our understanding of the pathogenesis of FSGS and guide prognosis of and therapy for hereditary glomerular kidney diseases.
TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization

Development of dendritic arbors is crucial for nervous system assembly, but the intracellular mechanisms that govern these processes remain incompletely understood. Here we show that the complex dendritic trees of PVD somatosensory neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine rich transmembrane (LRR-TM) receptor. The guanine nucleotide exchange factor tiam-1/GEF and act-4/Actin function with the DMA-1/LRR-TM to pattern 4° higher order branches by localizing F-actin to the distal ends of developing dendrites. Biochemical experiments show that DMA-1/LRR-TM is part of a biochemical complex with TIAM-1/GEF and ACT-4/Actin. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. Additionally, another pathway dependent on HPO-30/Claudin and TIAM-1/GEF is required for formation of 2° and 3° branches. Collectively, our experiments suggest that the DMA-1/LRR-TM receptor on PVD dendrites may control aspects of dendrite patterning by directly modulating F-actin dynamics, independently of TIAM-1/GEF enzymatic activity.
α-Tetralonyl Glucosides from the Green Walnut Husks of Juglans mandshurica and Their Antiproliferative Effects

Abstract Two new α-tetralonyl glucosides, (4S)-4,5,8-trihydroxy-α-tetralone-5-O-β-D-glucopyranosyl(1 → 6)-β-D-glucopyranoside (1) and (4S)-4,8-dihydroxy-α-tetralone-4-O-β-D-glucopyranosyl(1 → 6)-β-D-glucopyranoside (2), together with eight known compounds (3 – 10) were isolated from the green walnut husks of Juglans mandshurica. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS experiments. The isolated compounds were assayed for their cytotoxicity against two human cancer cell lines, A549 and HeLa. Four compounds (7 – 10) exhibited inhibitory effects against two human cancer cell lines with GI50 values between 1.3 and 5.8 µM.
Lung ultrasound for the diagnosis of acute heart failure: time to upgrade current indication?

Acute heart failure (AHF) is a potentially imminently life-threatening condition.1 Accurate and timely diagnosis already from the emergency department (ED) is crucial for the early initiation of appropriate therapies, a strategy that has been shown to improve clinical outcomes.2 However, differential diagnosis of patients presenting to the ED with acute dyspnoea remains challenging even in the current era of natriuretic peptides (NPs). NPs have significantly facilitated diagnostic work-up as excellent ‘rule out’ markers for AHF but are still limited by modest specificity and time-consuming logistics.3 Lung ultrasound (LUS) can diagnose lung congestion by the detection of bilateral B-lines, which represent increased extravascular lung water. Current European Society of Cardiology guidelines include LUS in the diagnostic work-up of acute dyspnoea but provide a weak indication (class IIb, level of evidence C) because of unavailability of data from randomized controlled studies.4 In this issue of the Journal, the study by Pivetta et al.5 is the first randomized controlled trial that examined the accuracy and clinical usefulness of a strategy that combines clinical assessment with LUS as compared to clinical assessment plus chest X-ray (CXR) and NP testing for the diagnosis of AHF. Two important findings emerge from this study. First, that the integrated strategy of clinical assessment plus LUS improves the diagnostic accuracy of clinical assessment whereas no such improvement was achieved by the combination of clinical assessment with CXR/NP testing. Moreover, the LUS strategy was superior to the CXR/NP strategy regarding clinical usefulness, as more patients with acute dyspnoea were correctly diagnosed upon presentation to the ED. Second, that the LUS integrated strategy substantially expedites final diagnosis compared to CXR/NP testing (by approximately 95%).
Comparing proxy rated quality of life of people living with dementia in care homes

Abstract Background Improving quality of life (QOL) for people with dementia is a priority. In care homes, we often rely on proxy ratings from staff and family but we do not know if, or how, they differ in care homes. Methods We compared 1056 pairs of staff and family DEMQOL-Proxy ratings from 86 care homes across England. We explored factors associated with ratings quantitatively using multilevel modelling and, qualitatively, through thematic analysis of 12 staff and 12 relative interviews. Results Staff and family ratings were weakly correlated (ρs = 0.35). Median staff scores were higher than family's (104 v. 101; p < 0.001). Family were more likely than staff to rate resident QOL as ‘Poor’ (χ2 = 55.91, p < 0.001). Staff and family rated QOL higher when residents had fewer neuropsychiatric symptoms and severe dementia. Staff rated QOL higher in homes with lower staff:resident ratios and when staff were native English speakers. Family rated QOL higher when the resident had spent longer living in the care home and was a native English. Spouses rated residents’ QOL higher than other relatives. Qualitative results suggest differences arise because staff felt good care provided high QOL but families compared the present to the past. Family judgements centre on loss and are complicated by decisions about care home placement and their understandings of dementia. Conclusion Proxy reports differ systematically between staff and family. Reports are influenced by the rater:staff and family may conceptualise QOL differently.
A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants

ABSTRACT Background: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant. Methods: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12–15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants. Results: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant. Conclusion: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.
Long‐Term Treatment With TNF‐Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis

The aim of this cohort study was to evaluate the long‐term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X‐rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score >1/>20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p = 0.03) with low hip BMD and 25.3% (p < 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score ≥2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters—the ankylosing spondylitis disease activity scale, the C‐reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index—decreased significantly (p < 0.001). The mean radiological progression (n = 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p < 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration. © 2019 American Society for Bone and Mineral Research.
Visualisierung des emotionalen Ausdrucks in der Stimme

In unserem Leben sind wir tagtaglich mit Emotionen konfrontiert, seien es unsere eigenen, die unserer Freunde oder die der Verkauferin im Supermarkt. Einen emotionsfreien Zustand gibt es nicht. Emotionen drucken wir nicht nur durch Worte aus, die wir sagen, sondern auch durch Gesten, Korperhaltung und Artikulierung. Diese Arbeit beschaftigt sich mit der Visualisierung von Emotionen durch Farben, Formen und Animationen. Ihr liegt ein Emotionserkennungsprogramm zugrunde, welches anhand des Ausdrucks in der Stimme die Emotion klassifiziert. Zunachst wird der Begriff Emotion definiert und verschiedene Modelle der Emotionstheorie vorgestellt. Anhand von Farb- und Formsymbolik wird schlieslich die Visualisierung der Emotionen entworfen. Zum Schluss werden die Visualisierungen in ein Programm integriert, das mit dem Emotionserkenner interagiert. Da es sich bei dieser Arbeit um den theoretischen Teil meiner Bachelorarbeit handelt, wird auch auf die Implementierung des Emotionsvisualisierungsprogramms und die Interaktion der einzelnen Komponenten eingegangen. Die Arbeit wurde betreut von Frau Thurid Vogt vom Lehrstuhl fur Multimediakonzepte und deren Anwendungen der Universitat Augsburg.
A Comparison of Principal Component-Based and Multivariate Regression of Cardiac Disease

Selecting factors suitable to use in a regression model is often a complicated process: the researcher strives to retain all theoretically important factors while avoiding high correlations among independent variables. This chapter models cardiac disease and compares the explanatory ability of component-based multivariate regression models, created through the use of principal component analysis (PCA), with that of direct variable-based, multivariate regression models. The variable-based demographic and socioeconomic model contains education, sex, and 3 age factors; in contrast, the component-based model contains age as well as several modifiable risk factors: education, income, family, and housing factors. Moreover, the latter model also has statistically higher explanatory power. Components made through data reduction techniques may not always be interpretable, but, given closer examination of individual components, a component-based model becomes more interpretable. Further, all important factors will potentially be present in models. As such, component-based modelling can be a useful tool for research and public health planning. A key limitation of this work, to be addressed in future research, is the use of a variable (cardiac catheterisation procedures) that remains a crude proxy for cardiovascular disease. More effective analysis will be performed as data becomes available. Exploration into the relationship of factor and their spatial patterns will also be considered.
Bleeding Complications in Warfarin-Treated Patients Admitted to the Emergency Department

Background Increased use of warfarin for the treatment and prophylaxis of many diseases has increased the frequency of adverse events. Emergency departments (EDs) are the first places where early interventions for bleeding and other complaints related to warfarin use are performed. This study assessed the characteristics of patients receiving warfarin and the risk factors for bleeding complication among those admitted to the ED. Methods Patients admitted to the ED for any reason other than trauma during a 1-year period were retrospectively reviewed. The study population consisted of 96 patients who had received warfarin and had an international normalized ratio (INR) ≥ 3. Patient demographics and medical history were recorded. Results The mean age of the patients (female, 52.1%) was 64.9 ± 14.5 years. Fatigue was the most common presenting complaint (61%). At least one major and/or minor bleeding event had occurred in 32 (33.3%) of the patients. Patients with (n = 32) and without (n = 64) bleeding complications did not significantly differ with respect to age, sex, reason for warfarin initiation, duration of warfarin use, concomitant diseases, and concurrent medications. There were also no significant differences in the distribution of patient admissions in terms of season at presentation, INR level, and weekly warfarin dose. Conclusions While the parameters evaluated in this study did not significantly differ among warfarin-treated patients, they may nonetheless pose a risk of bleeding. Further large-scale and long-term studies that take into account biological variation are required to precisely identify the risk factors for bleeding.
Fluoxetine increases astrocytic glucose uptake and glycolysis in corticosterone-induced depression through restricting GR-TXNIP-GLUT1 Pathway

Antidepressant fluoxetine can affect cerebral glucose metabolism in clinic, but the underlying molecular mechanism remains poorly understood. Here, we examined the effect of fluoxetine on brain regional glucose metabolism in a rat model of depression induced by repeated corticosterone injection, and explored the molecular mechanism. Fluoxetine was found to recover the decrease of 18F-fluorodeoxyglucose (18F-FDG) signal in prefrontal cortex (PFC), and increased 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG, a fluorescent glucose analog) uptake in an astrocyte-specific manner in ex vivo cultured PFC slices from corticosterone-induced depressive rats, which were consistent with its improvement of animal depressive behaviors. Furthermore, fluoxetine restricted nuclear translocation of glucocorticoid receptor (GR) to suppress the transcription of thioredoxin interacting protein (TXNIP). Subsequently, it promoted glucose transporter 1 (GLUT1)-mediated glucose uptake and glycolysis of PFC astrocytes through suppressing TXNIP expression under corticosterone-induced depressive state. More importantly, fluoxetine could improve glucose metabolism of corticosterone-stimulated astrocytes via TXNIP-GLUT1 pathway. These results demonstrated that fluoxetine increased astrocytic glucose uptake and glycolysis in corticosterone-induced depression via restricting GR-TXNIP-GLUT1 pathway. The modulation of astrocytic glucose metabolism by fluoxetine was suggested as a novel mechanism of its antidepressant action.
Do Children Have the Same Capacity to Perceive Affordances as Adults? An Investigation of Tool Selection and Use

This study investigated whether 5- to 11-year-old children perceive affordances in the same way as adults ( M age = 22.93, SD = 2.16) when presented with a task and four tools (nail in a block of wood and a hammer, rock, wrench, and comb; bucket of sand and a shovel, wooden block, rake, and tweezers; and a screw in a block of wood and a screwdriver, knife, dime, and crayon). Participants were asked to select the best tool and act on an object until all four assigned tools had been selected. No explicit instructions were provided because we were interested how task perception would influence tool selection and action. Results support the notion that the capacity to perceive affordances increases with age. Further-more, differences in the way in which 5-year-olds acted on the screw in a block of wood demonstrated that the ability to detect some affordances takes longer to refine. Findings help to further the understanding of the development of perception–action coupling.
Benefit of nephron sparing surgery translates into lower cancer specific mortality in patients with localized renal cell carcinoma.

National Comprehensive Centre Network (NCCN) (1), as well as European Association of Urology (EAU) (2) guidelines recommend partial nephrectomy (PN) as the treatment of choice for stage T1 renal cell carcinoma (RCC). This recommendation is based on the rationale for maximal renal function preservation, lower risk of cardiovascular events and lower rate of other-cause mortality (OCM) provided by PN, relative to radical nephrectomy (RN) (3-7). Additionally, PN provides equivalent cancer control rates, relative to RN (8).
Automatic Structuring of Breast Cancer Radiology Reports for Quality Assurance

Hospitals often set protocols based on well defined standards to maintain quality of patient reports. To ensure that the clinicians conform to the protocols, quality assurance of these reports is needed. Patient reports are currently written in free-text format, which complicates the task of quality assurance. In this paper, we present a machine learning based natural language processing system for automatic quality assurance of radiology reports on breast cancer. This is achieved in three steps: we i) identify the top level structure of the report, ii) check whether the information under each section corresponds to the section heading, iii) convert the free-text detailed findings in the report to a semi-structured format. Top level structure and content of report were predicted with an F1 score of 0.97 and 0.94 respectively using Support Vector Machine (SVM). For automatic structuring, our proposed hierarchical Conditional Random Field (CRF) outperformed the baseline CRF with an F1 score of 0.78 vs 0.71. The third step generates a semi-structured XML format of the free-text report, which helps to easily visualize the conformance of the findings to the protocols. This format also allows easy extraction of specific information for other purposes such as search, evaluation and research.