bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preaching and the Problem of Religious Authority in Medieval Islam
Authors: Berkey Jonathan P. 
Published: May 2021

Popular preachers, known by various terms including qāṣṣ (storyteller) and wā`iẓ (admonisher), played an important role in medieval Islamic society as conveyors of religious knowledge to the common people. Their prominence, and what their critics viewed as their unreliability and corruption, provoked an effort by the `ulamā’ (religious scholars) to restrict their activities. The scholars’ campaign against the popular preachers was part of their larger struggle against what they viewed as illicit innovation (bid`a). The popular preachers, however, had their defenders, including some prominent Sufis. The preachers were able to take advantage of the persistent informality of religious authority in medieval Islam, and so remained influential figures in shaping Islam as it was experienced by the general Muslim populace.
Looking for Thistles in Stone Gardens: The Cemeteries of Nova Scotia’s Scottish Immigrants1
Authors: Stanley-Blackwell Laurie , Linkletter Michael 
Published: May 2021

By focusing on the burial sites of northeastern Nova Scotia’s Scottish immigrants, this article demonstrates that their cemeteries were varied and complex places, which defy a uniform reading. An analysis of such metrics as Gaelic language use, stated place of origin (i.e., parish, county, Scotland or North Britain), prevalence of thistle images and Christian iconography gives a verbal and visual dimension to the discussion of whether death was a catalyst for conformist expression among Scottish immigrants and whether they opted for pictorial or linguistic signifiers of identity. In their cemeteries, Scottishness was negotiated, new meanings of belonging forged, status aspirations articulated, and religious differences spatially enforced. It is in their last resting places that one sees vividly displayed the forces of change and continuity, tradition and innovation, and retention and adjustment, which reshaped their lives and deaths as immigrants.
Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents
Authors: Maslowska-Jarzyna Krystyna , Korczak Maria L. , Chmielewski Michał J. 
Published: May 2021

Artificial chloride transporters have been intensely investigated in view of their potential medicinal applications. Recently, we have established 1,8-diamidocarbazoles as a versatile platform for the development of active chloride carriers. In the present contribution, we investigate the influence of various electron-withdrawing substituents in positions 3 and 6 of the carbazole core on the chloride transport activity of these anionophores. Using lucigenin assay and large unilamellar vesicles as models, the 3,6-dicyano- and 3,6-dinitro- substituted receptors were found to be highly active and perfectly deliverable chloride transporters, with EC50,270s value as low as 22 nM for the Cl−/NO3− exchange. Mechanistic studies revealed that diamidocarbazoles form 1:1 complexes with chloride in lipid bilayers and facilitate chloride/nitrate exchange by carrier mechanism. Furthermore, owing to its increased acidity, the 3,6-dinitro- substituted receptor acts as a pH-switchable transporter, with physiologically relevant apparent pKa of 6.4.
Solution-Processed Pure Blue Thermally Activated Delayed Fluorescence Emitter Organic Light-Emitting Diodes With Narrowband Emission
Authors: Xu Ting , Liang Xiao , Xie Guohua 
Published: May 2021

There is a need to satisfy the high color purity requirement of display technology with a simply fabricated process. Herein, solution-processed blue thermally activated delayed fluorescence organic light-emitting diodes (OLEDs) with a narrow spectrum with a full width at half maximum (FWHM) of 32 nm and y color coordinate below 0.2 are demonstrated by employing a molecule containing boron and nitrogen atoms (TBN-TPA) as the guest emitter in the emissive layer. The opposite resonance positions of B-N atoms of TBN-TPA endows a multi-resonance effect, leading to high color purity.
RT-qPCR Assays for Rapid Detection of the N501Y, 69-70del, K417N, and E484K SARS-CoV-2 Mutations: A Screening Strategy to Identify Variants With Clinical Impact
Authors: Vega-Magaña Natali , Sánchez-Sánchez Rocío , Hernández-Bello Jorge , Venancio-Landeros Alberto Antony , Peña-Rodríguez Marcela , Vega-Zepeda Rosa Alejandra , Galindo-Ornelas Byron , Díaz-Sánchez Mauricio , García-Chagollán Mariel , Macedo-Ojeda Gabriela , García-González Octavio Patricio , Muñoz-Valle José Francisco 
Published: May 2021

BackgroundSeveral variants of the SARS-CoV-2 have been documented globally during the current COVID-19 pandemic. The N501Y, 69-70del, K417N, and E484K SARS-CoV-2 mutations have been documented among the most relevant due to their potential pathogenic biological effects. This study aimed to design, validate, and propose a fast real-time RT-qPCR assay to detect SARS-CoV-2 mutations with possible clinical and epidemiological relevance in the Mexican population.MethodsTargeting spike (S) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing. These assays were applied in clinical samples of 1060 COVID-19 patients from Jalisco Mexico.ResultsIn silico analyzes showed high specificity of the three assays. Amplicons of samples were confirmed through sequencing. The screening of samples of COVID-19 patients allowed the identification of the E484K mutation in nine individuals and the identification of P.2 Brazilian variant in Mexico.ConclusionThis work provides low-cost RT-qPCR assays for rapid screening and molecular surveillance of mutations with potential clinical impact. This strategy allowed the detection of E484K mutation and P.2 variant for the first time in samples from the Mexican population.
High-Wind Drag Coefficient Based on the Tropical Cyclone Simulated With the WRF-LES Framework
Authors: Jiang Wenrui , Wu Liguang , Liu Qingyuan 
Published: May 2021

The numerical simulation of tropical cyclones has been increasingly conducted using the advanced Weather Research and Forecast (WRF) model with the large-eddy simulation (LES) technique. Given the importance of the boundary wind profile for the vertical exchange of horizontal momentum between the atmosphere and the ocean, the drag coefficient was evaluated in the numerical simulation with the WRF-LES framework at the finest horizontal grid spacing of 37 m. In the absence of the TC–ocean interaction, the drag coefficient derived from the simulated wind profile does not show the leveling off or decrease in the strong wind conditions. The drag coefficient increases with the increasing near-surface wind speed and agrees well with the extrapolation of the Large and Pond formula in the strong wind conditions. It is suggested that the boundary wind structure simulated with the LES technique may be unrealistic when the TC–ocean interaction is not fully considered.
Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain
Authors: Shi Feitong , He Yudan , Chen Yao , Yin Xinman , Sha Xianzheng , Wang Yin 
Published: May 2021

Background: Neurodegenerative Diseases (NDs) are age-dependent and include Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), and so on. There have been numerous studies showing that accelerated aging is closely related (even the driver of) ND, thus promoting imbalances in cellular homeostasis. However, the mechanisms of how different ND types are related/triggered by advanced aging are still unclear. Therefore, there is an urgent need to explore the potential markers/mechanisms of different ND types based on aging acceleration at a system level.Methods: AD, PD, PSP, FTD, and aging markers were identified by supervised machine learning methods. The aging acceleration differential networks were constructed based on the aging score. Both the enrichment analysis and sensitivity analysis were carried out to investigate both common and specific mechanisms among different ND types in the context of aging acceleration.Results: The extracellular fluid, cellular metabolisms, and inflammatory response were identified as the common driving factors of cellular homeostasis imbalances during the accelerated aging process. In addition, Ca ion imbalance, abnormal protein depositions, DNA damage, and cytoplasmic DNA in macrophages were also revealed to be special mechanisms that further promote AD, PD, PSP, and FTD, respectively.Conclusion: The accelerated epigenetic aging mechanisms of different ND types were integrated and compared through our computational pipeline.
The Long Pentraxin PTX3 Controls Klebsiella Pneumoniae Severe Infection
Authors: Asgari Fatemeh , Supino Domenico , Parente Raffaella , Polentarutti Nadia , Stravalaci Matteo , Porte Remi , Pasqualini Fabio , Barbagallo Marialuisa , Perucchini Chiara , Recordati Camilla , Magrini Elena , Mariancini Andrea , Riva Federica , Giordano Alessia , Davoudian Sadaf , Roger Thierry , Veer Cornelis van’t , Jaillon Sebastien , Mantovani Alberto , Doni Andrea , Garlanda Cecilia 
Published: May 2021

Klebsiella pneumoniae is a common pathogen in human sepsis. The emergence of multidrug-resistant K. pneumoniae strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against K. pneumoniae infections using Ptx3-/- mice and mouse models of severe K. pneumoniae infections. Local and systemic PTX3 expression was induced following K. pneumoniae pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of K. pneumoniae infection revealed that PTX3 did not interact with K. pneumoniae, or promote opsonophagocytosis. The comparison of susceptibility of wild-type, Ptx3-/-, C3-/- and Ptx3-/-/C3-/- mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in Ptx3-/- mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of K. pneumoniae infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections.
Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models
Authors: Stamoula Eleni , Siafis Spyridon , Dardalas Ioannis , Ainatzoglou Alexandra , Matsas Alkis , Athanasiadis Theodoros , Sardeli Chrysanthi , Stamoulas Konstantinos , Papazisis Georgios 
Published: May 2021

BackgroundIncreased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy.ObjectiveThis review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients.MethodsThrough a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria.ResultsIn vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS.ConclusionAntidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.
Broad T Cell Targeting of Structural Proteins After SARS-CoV-2 Infection: High Throughput Assessment of T Cell Reactivity Using an Automated Interferon Gamma Release Assay
Authors: Brand Isabel , Gilberg Leonard , Bruger Jan , Garí Mercè , Wieser Andreas , Eser Tabea M. , Frese Jonathan , Ahmed Mohamed I. M. , Rubio-Acero Raquel , Guggenbuehl Noller Jessica M. , Castelletti Noemi , Diekmannshemke Jana , Thiesbrummel Sophie , Huynh Duc , Winter Simon , Kroidl Inge , Fuchs Christiane , Hoelscher Michael , Roider Julia , Kobold Sebastian , Pritsch Michael , Geldmacher Christof 
Published: May 2021

BackgroundAdaptive immune responses to structural proteins of the virion play a crucial role in protection against coronavirus disease 2019 (COVID-19). We therefore studied T cell responses against multiple SARS-CoV-2 structural proteins in a large cohort using a simple, fast, and high-throughput approach.MethodsAn automated interferon gamma release assay (IGRA) for the Nucleocapsid (NC)-, Membrane (M)-, Spike-C-terminus (SCT)-, and N-terminus-protein (SNT)-specific T cell responses was performed using fresh whole blood from study subjects with convalescent, confirmed COVID-19 (n = 177, more than 200 days post infection), exposed household members (n = 145), and unexposed controls (n = 85). SARS-CoV-2-specific antibodies were assessed using Elecsys® Anti-SARS-CoV-2 (Ro-N-Ig) and Anti-SARS-CoV-2-ELISA (IgG) (EI-S1-IgG).Results156 of 177 (88%) previously PCR confirmed cases were still positive by Ro-N-Ig more than 200 days after infection. In T cells, most frequently the M-protein was targeted by 88% seropositive, PCR confirmed cases, followed by SCT (85%), NC (82%), and SNT (73%), whereas each of these antigens was recognized by less than 14% of non-exposed control subjects. Broad targeting of these structural virion proteins was characteristic of convalescent SARS-CoV-2 infection; 68% of all seropositive individuals targeted all four tested antigens. Indeed, anti-NC antibody titer correlated loosely, but significantly with the magnitude and breadth of the SARS-CoV-2-specific T cell response. Age, sex, and body mass index were comparable between the different groups.ConclusionSARS-CoV-2 seropositivity correlates with broad T cell reactivity of the structural virus proteins at 200 days after infection and beyond. The SARS-CoV-2-IGRA can facilitate large scale determination of SARS-CoV-2-specific T cell responses with high accuracy against multiple targets.
Random Survival Forests to Predict Disease Control for Hepatocellular Carcinoma Treated With Transarterial Chemoembolization Combined With Sorafenib
Authors: Zhong Bin-Yan , Yan Zhi-Ping , Sun Jun-Hui , Zhang Lei , Hou Zhong-Heng , Zhu Xiao-Li , Wen Ling , Ni Cai-Fang 
Published: May 2021

Objectives: To use baseline variables to predict one-year disease control for patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as initial treatment by applying a machine learning approach based on the random survival forest (RF) model.Materials and Methods: The multicenter retrospective study included 496 patients with HCC treated with TACE combined with sorafenib between January 2014 and December 2018. The independent risk factors associated with one-year disease control (complete response, partial response, stable disease) were identified using the RF model, and their predictive importance was determined using the Gini index. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors.Results: The median overall survival was 15.5 months. A total of 186 (37.5%) patients achieved positive one-year disease control. The Barcelona Clinic Liver Cancer (BCLC) stage (Gini index: 20.0), tumor size (≤7 cm, &gt;7 cm; Gini index: 9.0), number of lobes involved (unilobar, bilobar; Gini index: 6.4), alpha-fetoprotein level (≤200 ng/dl, &gt;200 ng/dl; Gini index: 6.1), albumin–bilirubin grade (Gini index: 5.7), and number of lesions (1, &gt;1; Gini index: 5.3) were identified as independent risk factors, with the BCLC stage as the most important variable. The RF model achieved a higher concordance index of 0.724 compared to that for the logistic regression model (0.709).Conclusions: The RF model is a simple and accurate approach for prediction of one-year disease control for patients with HCC treated with TACE combined with sorafenib.
Synergism of Zinc Oxide Quantum Dots with Antifungal Drugs: Potential Approach for Combination Therapy against Drug Resistant Candida albicans
Authors: Chand Preeti , Kumari Sangeeta , Mondal Neelima , Singh Surinder P. , Prasad Tulika 
Published: May 2021

Candidiasis caused by Candida albicans is one of the most common microbial infections. Azoles, polyenes, allylamines, and echinocandins are classes of antifungals used for treating Candida infections. Standard drug doses often become ineffective due to the emergence of multidrug resistance (MDR). This leads to the use of higher drug doses for prolonged duration, resulting in severe toxicity (nephrotoxicity and liver damage) in humans. However, combination therapy using very low concentrations of two or more antifungal agents together, can lower such toxicity and limit evolution of drug resistance. Herein, 4–6 nm zinc oxide quantum dots (ZnO QDs) were synthesized and their in vitro antifungal activities were assessed against drug-susceptible (G1, F1, and GU4) and resistant (G5, F5, and GU5) isolates of C. albicans. In broth microdilution assay, ZnO QDs exhibited dose dependent growth inhibition between 0 – 200 µg/ml and almost 90% growth was inhibited in all Candida strains at 200 µg/ml of ZnO QDs. Synergy between ZnO QDs and antifungal drugs at sub-inhibitory concentrations of each was assessed by checkerboard analysis and expressed in terms of the fractional inhibitory concentration (FIC) index. ZnO QDs were used with two different classes of antifungals (azoles and polyenes) against Candida isolates: combination 1 (with fluconazole); combination 2 (with ketoconazole); combination 3 (with amphotericin B), and combination 4 (with nystatin). Results demonstrated that the potency of combinations of ZnO QDs with antifungal drugs even at very low concentrations of each was higher than their individual activities against the fungal isolates. The FIC index was found to be less than 0.5 for all combinations in the checkerboard assay, which confirmed synergism between sub-inhibitory concentrations of ZnO QDs (25 µg/ml) and individual antifungal drugs. Synergism was further confirmed by spot assay where cell viabilities of Candida strains were significantly reduced in all combinations, which was clearly evident from the disappearance of fungal cells on agar plates containing antifungal combinations. For safer clinical use, the in vitro cytotoxic activity of ZnO QDs was assessed against HeLa cell line and it was found that ZnO QDs were non-toxic at 25 µg/ml. Results suggested that the combination of ZnO QDs with drugs potentiate antimicrobial activity through multitargeted action. ZnO QDs could therefore offer a versatile alternative in combination therapy against MDR fungal pathogens, wherein lowering drug concentrations could reduce toxicity and their multitargeted action could limit evolution of fungal drug resistance.
Clinical Diagnostic Criteria Have a High Impact on the Frequency of Dementia in Late-Stage Parkinson's Disease
Authors: Severiano e Sousa Catarina , Fabbri Margherita , Godinho Catarina , Simões Rita , Chendo Inês , Coelho Miguel , Martins Isabel Pavão , Ferreira Joaquim J. 
Published: May 2021

Background: Cognitive impairment is a potential late feature of Parkinson's disease (PD). However, studies in patients with late-stage PD are lacking due to the particular characteristics of this population.Objectives: To evaluate the frequency of dementia in late-stage PD patients and to assess the impact of using different diagnostic criteria.Methods: We conducted a cross-sectional study to estimate the frequency of dementia in late-stage PD patients using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria as the primary outcome. We also applied other diagnostic criteria [MDS (Level I), DSM-IV, and DSM-5 criteria] to determine their applicability and impact on dementia frequency.Results: 93 participants with a mean age of 75.8 years (SD 6.8) and 16.5 years (SD 7.5) of disease duration were included. 64.3% were classified as demented using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria. We observed a high discrepancy on the frequency of dementia depending on the criteria applied [6.2% with MDS (Level I), 58.8% with DSM-IV, and 72.0% with DSM-5 criteria].Conclusions: We found a frequency of dementia below what was observed in similar populations. The particular characteristics of our sample may have contributed as protective factors for late-stage dementia. Dementia frequency varied depending on the criteria used mainly due to the presence of major depression.
Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period
Authors: Zhang Luping , Huang Jinwen , Zhang Zhengxiang , Cao Zhijian 
Published: May 2021

Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.