bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium-glucose co-transporter 2 inhibition as a mitochondrial therapy for atrial fibrillation in patients with diabetes?
Authors: Yurista Salva R. , Silljé Herman H. W. , Rienstra Michiel , de Boer Rudolf A. , Westenbrink B. Daan 
Published: January 2020

AbstractWhile patients with type 2 diabetes mellitus (T2DM) are at increased risk to develop atrial fibrillation (AF), the mechanistic link between T2DM and AF-susceptibility remains unclear. Common co-morbidities of T2DM, particularly hypertension, may drive AF in the setting of T2DM. But direct mechanisms may also explain this relation, at least in part. In this regard, recent evidence suggests that mitochondrial dysfunction drives structural, electrical and contractile remodelling of atrial tissue in patients T2DM. Mitochondrial dysfunction may therefore be the mechanistic link between T2DM and AF and could also serve as a therapeutic target. An elegant series of experiments published in Cardiovascular Diabetology provide compelling new evidence to support this hypothesis. Using a model of high fat diet (HFD) and low-dose streptozotocin (STZ) injection, Shao et al. provide data that demonstrate a direct association between mitochondrial dysfunction and the susceptibility to develop AF. But the authors also demonstrated that the sodium-glucose co-transporter 2 inhibitors (SGLT2i) empagliflozin has the capacity to restore mitochondrial function, ameliorate electrical and structural remodelling and prevent AF. These findings provide a new horizon in which mitochondrial targeted therapies could serve as a new class of antiarrhythmic drugs.
Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis
Authors: de Araujo Leonardo Silva , Pessler Kevin , Sühs Kurt-Wolfram , Novoselova Natalia , Klawonn Frank , Kuhn Maike , Kaever Volkhard , Müller-Vahl Kirsten , Trebst Corinna , Skripuletz Thomas , Stangel Martin , Pessler Frank 
Published: January 2020

Abstract
Background
The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis.

Methods
We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell’s palsy, Tourette syndrome, normal pressure hydrocephalus).

Results
PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman’s ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis.

Conclusions
Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.
Multi-omic serum biomarkers for prognosis of disease progression in prostate cancer
Authors: Kiebish Michael A. , Cullen Jennifer , Mishra Prachi , Ali Amina , Milliman Eric , Rodrigues Leonardo O. , Chen Emily Y. , Tolstikov Vladimir , Zhang Lixia , Panagopoulos Kiki , Shah Punit , Chen Yongmei , Petrovics Gyorgy , Rosner Inger L. , Sesterhenn Isabell A. , McLeod David G. , Granger Elder , Sarangarajan Rangaprasad , Akmaev Viatcheslav , Srinivasan Alagarsamy , Srivastava Shiv , Narain Niven R. , Dobi Albert 
Published: January 2020

AbstractBackgroundPredicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients ‘sera using a multi-omics discovery platform.MethodsPre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan–Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort.ResultsAmong 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins—Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite—1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98–14.40),P < 0.05], in differentiating patients with and without BCR event. In the validation set all four metabolites consistently reproduced an equivalent performance with high negative predictive value (NPV; > 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45–32.05,P < 0.05], with an increased NPV (0.96) and OR (12.4) for BCR. The panel of markers combined with the pathological parameters demonstrated a more accurate prediction of BCR than the pathological parameters alone in prostate cancer.ConclusionsIn this study, a panel of serum analytes were identified that complemented pathologic patient features in predicting prostate cancer progression. This panel offers a new opportunity to complement current prognostic markers and to monitor the potential impact of primary treatment versus surveillance on patient oncological outcome.
Malignant transformation of oral leukoplakia is associated with macrophage polarization
Authors: Weber Manuel , Wehrhan Falk , Baran Christoph , Agaimy Abbas , Büttner-Herold Maike , Öztürk Hatice , Neubauer Kristina , Wickenhauser Claudia , Kesting Marco , Ries Jutta 
Published: January 2020

AbstractBackgroundMost oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization.Methods201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann–Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2test).ResultsMacrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05).ConclusionImmunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.
Future treatments for hereditary hemorrhagic telangiectasia
Authors: Robert Florian , Desroches-Castan Agnès , Bailly Sabine , Dupuis-Girod Sophie , Feige Jean-Jacques 
Published: January 2020

AbstractHereditary Hemorrhagic Telangiectasia(HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations ofACVRL1orENGgenes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the geneSMAD4which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients.
A new phenothiazine-based selective visual and fluorescent sensor for cyanide
Authors: Al-Zahrani Fatimah A. M. , El-Shishtawy Reda M. , Asiri Abdullah M. , Al-Soliemy Amerah M. , Mellah Khloud Abu , Ahmed Nahed S. E. , Jedidi Abdesslem 
Published: January 2020

AbstractA new donor-π-acceptor derived from phenothiazine, namely 2-(2-((10-hexyl-10H-phenothiazin-3-yl)methylene)-3-oxo-2,3-dihydroinden-1-ylidene) malononitrile (PTZON) was synthesized and fully characterized, and its potential as a fluorescent sensor for cyanide anion was investigated. The PTZON showed a visible absorption band at 564 nm corresponds to an intramolecular charge transfer (ICT) and an emission band at 589 nm in CH3CN/H2O. The results of cyanide anion titration revealed ratiometric changes in both absorption and fluorescence spectra as a result of the nucleophilic addition of cyanide anion via Michael addition. The optical studies, FT-IR spectra, NMR, high-resolution mass, and DFT calculations confirmed the sensing mechanism. The selectivity of PTZON as a cyanide anion fluorescent sensor was proved in mixed solvent solutions, and the sensitivity was as low as 0.011 µM, which is far lower than the value allowed by the United States Environmental Protection Agency for drinking water (1.9 µM). Also, the detection limit of PTZON was assessed to be 3.39 μM by the spectrophotometric method. The binding stoichiometry between PTZON and cyanide anion was found to be 1:1 as evidenced by mass spectra. TLC silica-coated plates test strips demonstrated the fluorescent detection of cyanide anion.
Barriers to treatment optimization and achievement of patients’ goals: perspectives from people living with rheumatoid arthritis enrolled in the ArthritisPower registry
Authors: Gavigan Kelly , Nowell W. Benjamin , Serna Mylene S. , Stark Jeffrey L. , Yassine Mohamed , Curtis Jeffrey R. 
Published: January 2020

Abstract
Background
Few studies have investigated patients’ own treatment goals in rheumatoid arthritis (RA). The objective of this real-world, cross-sectional study of US patients with RA was to identify factors that patients believed influenced their physician’s treatment decisions. Secondary objectives included reasons patients tolerated sub-optimal disease control and their perceived barriers to treatment optimization.

Methods
Eligible participants were enrolled in the ArthritisPower registry, ≥ 19 years, had physician-diagnosed RA, unchanged treatment within 3 months of baseline, prior/current disease-modifying antirheumatic drug treatment (DMARDs), and computer/smartphone access. In December 2017, participants completed Patient-Reported Outcomes Measurement Information System-Computerized Adaptive Tests (PROMIS-CAT) for pain interference, fatigue, sleep disturbance, and physical function. Routine Assessment of Patient Index Data 3 (RAPID3) provided disease activity scores (0–30). Participants completed an online survey on barriers to treatment optimization, including self-perception of disease compared to RAPID3/PROMIS scores.

Results
A total of 249 participants met inclusion criteria and completed the survey. Mean age (SD) was 52 (11) years, and the majority were female (92%) with high RAPID3 disease activity (175/249 [70%]; median score 18). The main reason participants did not change treatment was their physician’s recommendation (66%; n = 32). Of participants with high RAPID3 disease activity, 66 (38%) were offered a treatment change; 19 (29%) of whom declined the change. Most participants who intensified treatment did so because their symptoms had remained severe or worsened (51%; n = 33); only 16 (25%) participants intensified because they had not reached a specified treatment goal. Among participants who self-reported their disease activity as “none/low” or “medium” (n = 202; 81% of cohort), most still had RAPID3 high disease activity (137/202 [68%]; score > 12). Most PROMIS scores showed moderate agreement with participants’ self-assessment of health status, in contrast to RAPID3 (weighted kappa: 0.05 [95% CI − 0.01, 0.11]).

Conclusions
Most participants trusted their rheumatologist’s treatment decisions and prioritized their physician’s treatment goals over their own. Patients should be encouraged to share their treatment goals/expectations with their rheumatologist, in line with the treat-to-target approach. RAPID3 may be inappropriate for setting patient-centric treatment goals given the poor agreement with self-reported disease activity; most PROMIS scores showed better alignment with patients’ own assessments.
Automatic load sharing of distribution transformer for overload protection
Authors: Nebey Abraham Hizkiel 
Published: January 2020

AbstractObjectiveLoad sharing provides sufficient protection to distribution transformer under overloaded conditions. Due to overload on transformer, the efficiency drops and windings get overheated and may burn. By sharing a load current on transformer for each phase the transformer was protected. Therefore, the objective of this study was to protect transformers from overloaded conditions by sharing the load.ResultThe system automatically connects and disconnects switch to share the transformer loads. The controller was managed the load according to rules.
Does training location matter? Evidence from a randomized field experiment in Rural Indonesia
Authors: Pratiwi Ayu , Suzuki Aya 
Published: January 2020

AbstractInformal network helps disseminate agricultural knowledge in the rural area where formal extension is lacking. However, how the interplay between formal training and informal network promotes technology adoption is still under-studied. This paper aims to examine the effects of training locations upon knowledge and adoption of agricultural techniques via strengthened informal and formal social networks. We administer agricultural training of identical contents in farmers’ hometown and in more remote but advanced locations and arrange farmers to travel to the respective locations. Then, we examine locational heterogeneity effects upon conservation and plant-rehabilitation techniques, and social network variables with formal extension services, informal network, and between participants and non-participants. Only farmers trained in the most remote location increase the size and depth of social network with their peers, extension expert, and non-participants upon returning from training. These changes in social networks may encourage them to adopt the technology. While formal training is important for knowledge diffusion, informal network is the key for successful adoption, and these networks are strengthened via training held in the most remote location.
Role of absence in academic success: an analysis using visualization tools
Authors: Etemadpour Ronak , Zhu Yongcheng , Zhao Qizhi , Hu Yilun , Chen Bohan , Sharier Mohammed Asif , Zheng Shirong , S. Paiva Jose Gustavo 
Published: January 2020

AbstractUnderstanding the academic performance of students in colleges is an essential topic in Education research field. Educators, program coordinators and professors are interested in understanding how students are learning specific topics, how specific topics may influence the learning of other topics, how students’ grades/attendances in each course may represent important indicators to measure their performance, among other tasks. The use of data visualization and analytics is expanding in education institutions to perform a variety of tasks related to data processing and gaining into data-informed insights. In this paper, we present a visual analytic tool that combines data visualization and machine learning techniques to perform some visual analysis of students’ data from program courses. Two educational data collections were used to guide the creation of i) predictive models employing a variety of well known machine learning strategies, attempting to predict students’ future grade based on grade and attendance previous semesters and ii) a set interactive layouts that highlight the relationship between grades and attendance, also including additional variables such as gender, parents education level, among others. We performed several experiments, also using these data collections, to evaluate the layouts ability of highlighting interesting patterns, and we obtained promising results, demonstrating that such analysis may help the education experts to understand deficiencies on course structures.
Bacterial cytochrome P450-catalyzed regio- and stereoselective steroid hydroxylation enabled by directed evolution and rational design
Authors: Zhang Xiaodong , Peng Yaqin , Zhao Jing , Li Qian , Yu Xiaojuan , Acevedo-Rocha Carlos G. , Li Aitao 
Published: January 2020

AbstractSteroids are the most widely marketed products by the pharmaceutical industry after antibiotics. Steroid hydroxylation is one of the most important functionalizations because their derivatives enable a higher biological activity compared to their less polar non-hydroxylated analogs. Bacterial cytochrome P450s constitute promising biocatalysts for steroid hydroxylation due to their high expression level in common workhorses like Escherichia coli. However, they often suffer from wrong or insufficient regio- and/or stereoselectivity, low activity, narrow substrate range as well as insufficient thermostability, which hampers their industrial application. Fortunately, these problems can be generally solved by protein engineering based on directed evolution and rational design. In this work, an overview of recent developments on the engineering of bacterial cytochrome P450s for steroid hydroxylation is presented.
General election effect on the network topology of Pakistan’s stock market: network-based study of a political event
Authors: Memon Bilal Ahmed , Yao Hongxing , Tahir Rabia 
Published: January 2020

AbstractTo examine the interdependency and evolution of Pakistan’s stock market, we consider the cross-correlation coefficients of daily stock returns belonging to the blue chip Karachi stock exchange (KSE-100) index. Using the minimum spanning tree network-based method, we extend the financial network literature by examining the topological properties of the network and generating six minimum spanning tree networks around three general elections in Pakistan. Our results reveal a star-like structure after the general elections of 2018 and before those in 2008, and a tree-like structure otherwise. We also highlight key nodes, the presence of different clusters, and compare the differences between the three elections. Additionally, the sectorial centrality measures reveal economic expansion in three industrial sectors—cement, oil and gas, and fertilizers. Moreover, a strong overall intermediary role of the fertilizer sector is observed. The results indicate a structural change in the stock market network due to general elections. Consequently, through this analysis, policy makers can focus on monitoring key nodes around general elections to estimate stock market stability, while local and international investors can form optimal diversification strategies.
Process intensification technologies for CO2 capture and conversion – a review
Authors: Adamu Abdullahi , Russo-Abegão Fernando , Boodhoo Kamelia 
Published: January 2020

AbstractWith the concentration of CO2in the atmosphere increasing beyond sustainable limits, much research is currently focused on developing solutions to mitigate this problem. Possible strategies involve sequestering the emitted CO2for long-term storage deep underground, and conversion of CO2into value-added products. Conventional processes for each of these solutions often have high-capital costs associated and kinetic limitations in different process steps. Additionally, CO2is thermodynamically a very stable molecule and difficult to activate. Despite such challenges, a number of methods for CO2capture and conversion have been investigated including absorption, photocatalysis, electrochemical and thermochemical methods. Conventional technologies employed in these processes often suffer from low selectivity and conversion, and lack energy efficiency. Therefore, suitable process intensification techniques based on equipment, material and process development strategies can play a key role at enabling the deployment of these processes. In this review paper, the cutting-edge intensification technologies being applied in CO2capture and conversion are reported and discussed, with the main focus on the chemical conversion methods.