Miracle-dz/UniFAR-FTUs huggingface dataset:
Global brain volume reductions in a sub-chronic phencyclidine animal model for schizophrenia and their relationship to recognition memory

Background: Cognitive deficits and structural brain changes co-occur in patients with schizophrenia. Improving our understanding of the relationship between these is important to develop improved therapeutic strategies. Back-translation of these findings into rodent models for schizophrenia offers a potential means to achieve this goal. Aims: The purpose of this study was to determine the extent of structural brain changes and how these relate to cognitive behaviour in a sub-chronic phencyclidine rat model. Methods: Performance in the novel object recognition task was examined in female Lister Hooded rats at one and six weeks after sub-chronic phencyclidine (2 mg/kg intra-peritoneal, n=15) and saline controls (1 ml/kg intra-peritoneal, n=15). Locomotor activity following acute phencyclidine challenge was also measured. Brain volume changes were assessed in the same animals using ex vivo structural magnetic resonance imaging and computational neuroanatomical analysis at six weeks. Results: Female sub-chronic phencyclidine-treated Lister Hooded rats spent significantly less time exploring novel objects (p<0.05) at both time-points and had significantly greater locomotor activity response to an acute phencyclidine challenge (p<0.01) at 3–4 weeks of washout. At six weeks, sub-chronic phencyclidine-treated Lister Hooded rats displayed significant global brain volume reductions (p<0.05; q<0.05), without apparent regional specificity. Relative volumes of the perirhinal cortex however were positively correlated with novel object exploration time only in sub-chronic phencyclidine rats at this time-point. Conclusion: A sustained sub-chronic phencyclidine-induced cognitive deficit in novel object recognition is accompanied by global brain volume reductions in female Lister Hooded rats. The relative volumes of the perirhinal cortex however are positively correlated with novel object exploration, indicating some functional relevance.
Effects of acute intake of grape/pomegranate pomace dietary supplement on glucose metabolism and oxidative stress in adults with abdominal obesity

Abstract A controlled acute, cross-over clinical study (NCT02710461) was performed in order to evaluate the effects on glucose metabolism of a grape/pomegranate pomace dietary supplement in subjects with abdominal obesity (aged 40–60, n = 20). A standard 75 g oral glucose tolerance test (OGTT) was administered alone, together with or 10 h after the consumption of 10 g of the dietary supplement, rich in both extractable (0.4 g) and non-extractable (1.4 g) polyphenols. The dietary supplement did not ameliorate glucose or insulin at any sampling time. No improvement in antioxidant capacity was observed in plasma or urine, concordant with no increased urine polyphenol excretion. A tendency towards improved insulin sensitivity was observed when the product was consumed 10 h before glucose solution. These results suggest that a single realistic dose of grape/pomegranate pomace is not able to clearly improve glucose metabolism; chronic intake remains to be evaluated.
Disrupted Plasma Membrane Protein Homeostasis in a Xenopus Laevis Model of Retinitis Pigmentosa

Rhodopsin mislocalization is frequently observed in retinitis pigmentosa (RP) patients. For example, class I mutant rhodopsin is deficient in the VxPx trafficking signal, mislocalizes to the plasma membrane (PM) of rod photoreceptor inner segments (ISs), and causes autosomal dominant RP. Mislocalized rhodopsin causes photoreceptor degeneration in a manner independent of light-activation. In this manuscript, we took advantage of Xenopus laevis models of both sexes expressing wild-type human rhodopsin or its class I Q344ter mutant fused to Dendra2 fluorescent protein to characterize a novel light-independent mechanism of photoreceptor degeneration caused by mislocalized rhodopsin. We found that rhodopsin mislocalized to the PM is actively internalized and transported to lysosomes where it is degraded. This degradation process results in the downregulation of a crucial component of the photoreceptor IS PM: the sodium-potassium ATPase α-subunit (NKAα). The downregulation of NKAα is not because of decreased NKAα mRNA, but due to cotransport of mislocalized rhodopsin and NKAα to lysosomes or autophagolysosomes. In a separate set of experiments, we found that class I mutant rhodopsin, which causes NKAα downregulation, also causes shortening and loss of rod outer segments (OSs); the symptoms frequently observed in the early stages of human RP. Likewise, pharmacological inhibition of NKAα led to shortening and loss of rod OSs. These combined studies suggest that mislocalized rhodopsin leads to photoreceptor dysfunction through disruption of the PM protein homeostasis and compromised NKAα function. This study unveiled a novel role of lysosome-mediated degradation in causing inherited disorders manifested by mislocalization of ciliary receptors. SIGNIFICANCE STATEMENT Retinal ciliopathy is the most common form of inherited blinding disorder frequently manifesting rhodopsin mislocalization. Our understanding of the relationships between rhodopsin mislocalization and photoreceptor dysfunction/degeneration has been far from complete. This study uncovers a hitherto uncharacterized consequence of rhodopsin mislocalization: the activation of the lysosomal pathway, which negatively regulates the amount of the sodium-potassium ATPase (NKAα) on the inner segment plasma membrane. On the plasma membrane, mislocalized rhodopsin extracts NKAα and sends it to lysosomes where they are co-degraded. Compromised NKAα function leads to shortening and loss of the photoreceptor outer segments as observed for various inherited blinding disorders. In summary, this study revealed a novel pathogenic mechanism applicable to various forms of blinding disorders caused by rhodopsin mislocalization.
A dynamic network model of temporal receptive fields in primary auditory cortex

Auditory neurons encode stimulus history, which is often modelled using a span of time-delays in a spectro-temporal receptive field (STRF). We propose an alternative model for the encoding of stimulus history, which we apply to extracellular recordings of neurons in the primary auditory cortex of anaesthetized ferrets. For a linear-non-linear STRF model (LN model) to achieve a high level of performance in predicting single unit neural responses to natural sounds in the primary auditory cortex, we found that it is necessary to include time delays going back at least 200 ms in the past. This is an unrealistic time span for biological delay lines. We therefore asked how much of this dependence on stimulus history can instead be explained by dynamical aspects of neurons. We constructed a neural-network model whose output is the weighted sum of units whose responses are determined by a dynamic firing-rate equation. The dynamic aspect performs low-pass filtering on each unit’s response, providing an exponentially decaying memory whose time constant is individual to each unit. We find that this dynamic network (DNet) model, when fitted to the neural data using STRFs of only 25 ms duration, can achieve prediction performance on a held-out dataset comparable to the best performing LN model with STRFs of 200 ms duration. These findings suggest that integration due to the membrane time constants or other exponentially-decaying memory processes may underlie linear temporal receptive fields of neurons beyond 25 ms.
Development of a dynamic model of the European transmission system using publicly available data

The transition towards large-scale renewable electricity generation represents a potential challenge to the dynamic stability of the European power system. Problems such as reduced rotational inertia and inter-area oscillatory instability must be mitigated through new approaches to system planning and operation. However, the datasets required for accurate modeling of the European transmission system (such as location and type of lines, substations, generators and reactive compensation) are largely unavailable to the public. Therefore, the following paper presents a methodology for the development of a dynamic model of the ENTSO-E system using only publicly available data. All information sources are detailed and the methods used for estimation of unavailable data are described. The resulting model is used to perform load flow and time-domain simulations in the PSS®Netomac software and results are validated against published measurement data.
The N‐end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome activation by anthrax lethal toxin

Anthrax lethal toxin (LT) is known to induce NLRP1B inflammasome activation and pyroptotic cell death in macrophages from certain mouse strains in its metalloprotease activity‐dependent manner, but the underlying mechanism is unknown. Here, we establish a simple but robust cell system bearing dual‐fluorescence reporters for LT‐induced ASC specks formation and pyroptotic lysis. A genome‐wide siRNA screen and a CRISPR‐Cas9 knockout screen were applied to this system for identifying genes involved in LT‐induced inflammasome activation. UBR2, an E3 ubiquitin ligase of the N‐end rule degradation pathway, was found to be required for LT‐induced NLRP1B inflammasome activation. LT is known to cleave NLRP1B after Lys44. The cleaved NLRP1B, bearing an N‐terminal leucine, was targeted by UBR2‐mediated ubiquitination and degradation. UBR2 partnered with an E2 ubiquitin‐conjugating enzyme UBE2O in this process. NLRP1B underwent constitutive autocleavage before the C‐terminal CARD domain. UBR2‐mediated degradation of LT‐cleaved NLRP1B thus triggered release of the noncovalent‐bound CARD domain for subsequent caspase‐1 activation. Our study illustrates a unique mode of inflammasome activation in cytosolic defense against bacterial insults.
Utility analysis for topically biased PageRank

PageRank is known to be an efficient metric for computing general document importance in the Web. While commonly used as a one-size-fits-all measure, the ability to produce topically biased ranks has not yet been fully explored in detail. In particular, it was still unclear to what granularity of "topic" the computation of biased page ranks makes sense. In this paper we present the results of a thorough quantitative and qualitative analysis of biasing PageRank on Open Directory categories. We show that the MAP quality of Biased PageRank generally increases with the ODP level up to a certain point, thus sustaining the usage of more specialized categories to bias PageRank on, in order to improve topic specific search.
Contrast and Homogeneity Feature Analysis for Classifying Tremor Levels in Parkinson’s Disease Patients

Early detection of different levels of tremors helps to obtain a more accurate diagnosis of Parkinson’s disease and to increase the therapy options for a better quality of life for patients. This work proposes a non-invasive strategy to measure the severity of tremors with the aim of diagnosing one of the first three levels of Parkinson’s disease by the Unified Parkinson’s Disease Rating Scale (UPDRS). A tremor being an involuntary motion that mainly appears in the hands; the dataset is acquired using a leap motion controller that measures 3D coordinates of each finger and the palmar region. Texture features are computed using sum and difference of histograms (SDH) to characterize the dataset, varying the window size; however, only the most fundamental elements are used in the classification stage. A machine learning classifier provides the final classification results of the tremor level. The effectiveness of our approach is obtained by a set of performance metrics, which are also used to show a comparison between different proposed designs.
Potential of Liquid Extraction Surface Analysis Mass Spectrometry (LESA—MS) for the Characterization of Polymer-Based Materials

Liquid extraction surface analysis mass spectrometry (LESA -MS) is a direct analysis method suitable for the analysis of polymers. It is based on a fast and efficient extraction of polymer components, such as non-intentionally added species (NIAS), post-polymerization residues, or additives, and residues resulting from specific uses followed by their MS detection. In comparison with batch methods, it is a “green” method, using negligible volumes of organic solvents, and it is cost-effective, avoiding lengthy sample preparation procedures. It can be used for the detection of known molecules (targeted analysis), identification of unknown species (exploratory analysis requiring MS/MS) and semi-quantative analysis, if standards are available. The to-date applications of LESA-MS in the field of polymer science are reviewed and critically discussed taking into account the hands-on experience from the authors’ laboratory. Future possibilities of LESA applications are highlighted.
Prognosis of Papillary Thyroid Cancer

7 Age over 45 years, tumour size > 4 cm, extrathyroidal extension of tumour, nodal metastases, distant metastases, and stage IV disease signifi cantly correlated with survival. Expression of COX-2, Ki-67, and VEGF-C was higher in older patients, and expression of these markers correlated with stage, but not with other clinical parameters or aggressive disease. Among the patients with positive lymph nodes, most tumours of older patients expressed VEGF-C, but most of those younger patients did not. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly with each other. In cell culture studies, both VEGF-C and COX-2 were induced by phorbol 12-myristate 13-acetate (PMA), but the selective COX-2 inhibitor N-(2-Cyclohexyloxy-4-nitrophenyl)-Methanesulfonamide (NS398) did not reduce VEGF-C expression. Thus, correlation of COX-2 and VEGFC was not so clear. Stromal expression of MMP-2 correlated with the extent of the primary tumour and with advanced stage, but not with aggressive disease. Expression of p21 was higher in tumours extending beyond the thyroid capsule and in larger tumours, but expression did not correlate with aggressive disease. Expression of Bcl-2 correlated neither with clinical parameters nor aggressive disease. Most patients with papillary thyroid cancer can be cured if treated according to best clinical practice. In older patients, PTC is a more aggressive disease. Lymph node metastases (LNM) seemed to be predictive for distant metastases and death in older patients, but not at all for those younger. Unexpectedly, however, some young low-risk patients do suffer from aggressive disease. How to recognize these young patients is the problem. Although we found elevated expression of COX-2, VEGF-C, and Ki-67 in those older, these three markers did not predict patient outcome. Better understanding of differences in tumour biology in young and older patients may help us to select those young patients who display the tumour behaviour of older patients. Initial treatment and follow-up could be individualized according to age. Older lymph node-positive PTC patients may benefi t from more radical lymph node dissection. These patients may also benefi t from COX-2 selective inhibitors.
Con: Liver Biopsy Remains the Gold Standard to Evaluate Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting nearly 25% to 30% of the general population. The natural history of NAFLD includes the potential for progression to nonalcoholic steatohepatitis (NASH), followed by fibrosis and ultimately cirrhosis. Knowledge of fibrosis stage in NAFLD is important in the management of this disease because prior studies have shown that for each increase in stage of fibrosis, there is a significant decrease in transplant-free survival. Understanding an individual’s stage of fibrosis allows clinicians to manage their patients with interventions tailored to their specific stage, from simple diet and exercise to more advanced therapies, such as surgical interventions or pharmaceutical treatments including referral for clinical trials. Because liver biopsy provides a direct visualization of fibrosis, we believe that this modality remains the gold standard test in assessing fibrosis in NAFLD.
Sustained sensing in potassium homeostasis: Cyclic di-AMP controls potassium uptake by KimA at the levels of expression and activity

The signaling nucleotide cyclic di-AMP (c-di-AMP) is the only known essential second messenger in bacteria. Recently, c-di-AMP has been identified as being essential for controlling potassium uptake in the model organism Bacillus subtilis and several other bacteria. A B. subtilis strain lacking c-di-AMP is not viable at high potassium concentrations, unless the bacteria acquire suppressor mutations. In this study, we isolated such suppressor mutants and found mutations that reduced the activities of the potassium transporters KtrCD and KimA. Although c-di-AMP–mediated control of KtrCD has previously been demonstrated, it is unknown how c-di-AMP affects KimA activity. Using the DRaCALA screening assay, we tested for any interactions of KimA and other potential target proteins in B. subtilis with c-di-AMP. This assay identified KimA, as well as the K+/H+ antiporter KhtT, the potassium exporter CpaA (YjbQ), the osmoprotectant transporter subunit OpuCA, the primary Mg2+ importer MgtE, and DarB (YkuL), a protein of unknown function, as bona fide c-di-AMP–binding proteins. Further, binding of c-di-AMP to KimA inhibited potassium uptake. Our results indicate that c-di-AMP controls KimA-mediated potassium transport at both kimA gene expression and KimA activity levels. Moreover, the discovery that potassium exporters are c-di-AMP targets indicates that this second messenger controls potassium homeostasis in B. subtilis at a global level by binding to riboswitches and to different classes of transport proteins involved in potassium uptake and export.
Macromolecules with Different Charges, Lengths, and Coordination Groups for the Coprecipitation Synthesis of Magnetic Iron Oxide Nanoparticles as T1 MRI Contrast Agents

Considerable efforts have been focused on the exploitation of macromolecule ligands for synthesis of magnetic Fe3O4 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents, but studies that concern macromolecule ligands with different charges and coordination groups are still limited. Herein, we used poly(acrylic acid) (PAA), poly(allylamine hydrochloride) (PAH), and polyvinyl alcohol (PVA), which possess negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups respectively, as templates and stabilizers to fabricate Fe3O4 nanoparticles through coprecipitation reaction. The obtained Fe3O4-PAA, Fe3O4-PAH, and Fe3O4-PVA nanoparticles showed T1 contrast performance with r1 relaxivities of 23.4, 60.3, and 30.6 mM s−1 at 0.5 T (25 °C), and a r2/r1 ratio of 2.62, 3.82, and 7.26, respectively. The cell viability assay revealed that Fe3O4-PAA and Fe3O4-PVA exhibited good biocompatibility, while Fe3O4-PAH displayed high cytotoxicity. In vivo T1-weighted (1 T) mice showed that both Fe3O4-PAA and Fe3O4-PVA were able to display remarkably brighten the contrast enhancement for the mice tumor and kidney sites, but Fe3O4-PAA had better contrast performance. This work highlights that the macromolecule ligands play an important role in the biocompatibility and T1 contrast performance of magnetic Fe3O4 nanoparticles.
Simplified Testing Method for Direct Detection of Carbapenemase-Producing Organisms from Positive Blood Cultures Using the NG-Test Carba 5 Assay

We directly tested 484 organisms from clinical (n = 310) and simulated (n = 174) positive blood cultures using the NG-Test Carba 5 assay for carbapenemase-producing Enterobacterales detection. The assay identified all but 4 of the KPC (170/171), OXA-48-like (22/22), VIM (19/21), and NDM (14/15) producers with no false positives. ABSTRACT We directly tested 484 organisms from clinical (n = 310) and simulated (n = 174) positive blood cultures using the NG-Test Carba 5 assay for carbapenemase-producing Enterobacterales detection. The assay identified all but 4 of the KPC (170/171), OXA-48-like (22/22), VIM (19/21), and NDM (14/15) producers with no false positives. Among the clinical Klebsiella pneumoniae organisms tested, 122 of 123 KPC, 1 of 1 OXA-48-like, and 1 of 2 VIM producers were detected by the assay. Some VIM and NDM producers yielded scant but still-readable bands with the assay. No organisms produced the IMPs that the assay was designed to detect.
Influence of Risk of Drug–Drug Interactions and Time Availability on Patient Trust, Satisfaction, and Cooperation with Clinical Pharmacists

Patients with multiple diseases requiring several medications often face the risk of drug–drug interactions (DDIs). Such patients need more care and services from clinical pharmacists. Given the importance of this issue in clinical medicine, the present study aims to investigate how DDIs and time availability affect patient trust in clinical pharmacists and how patient trust influences patient satisfaction and cooperation between patients and clinical pharmacists. Sample data of 741 patients in central Taiwan hospitals were analyzed, and the results of structural equation modeling showed that DDIs and time availability positively affect patient trust, which, in turn, positively influenced patient satisfaction and cooperation between patients and clinical pharmacists. Overall, the results indicated that patient satisfaction is an important predictor of cooperation between patients and clinical pharmacists.
RMCC: A ROLAP data model of minimal condensed Cube

Data cubes facilitate online analytical processing( OLAP) systems greatly. Ever since the Cube-by operator was introduced by Jim Gray in 1997, techniques for computing, compressing and efficiently accessing data cubes have been substantially studied due to the enormous storage size as the number of dimensions and dimension cardinalities increase. Minimal condensed cube, one of these data cube compressing schemes, was proposed and shown to be very effective especially for the environment of RDBMSs. Although efforts on fast computation and incremental update algorithms of Minimal condensed cube has been made by researchers, a totally RDBMS based data storage model has not been investigated, which is a key issue in data cube implementation. In this paper, we proposed RMCC(relational Minimal condensed cube), a pure ROLAP-based data model for the storage structure of Minimal condensed cube. We model RMCC not only to further reduce the storage cost of Minimal condensed cube, but also that queries can be answered efficiently by mature relational database engines. We proposed a SQL framework for answering OLAP queries over RMCC by the stored procedure/function technique supported by SQL:2003.