bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of admission hyperglycaemia on clinical outcomes in non‐diabetic heart failure with preserved ejection fraction
Authors: Yano Masamichi , Nishino Masami , Ukita Kohei , Kawamura Akito , Nakamura Hitoshi , Matsuhiro Yutaka , Yasumoto Koji , Tsuda Masaki , Okamoto Naotaka , Tanaka Akihiro , Matsunaga‐Lee Yasuharu , Egami Yasuyuki , Shutta Ryu , Tanouchi Jun , Yamada Takahisa , Yasumura Yoshio , Tamaki Shunsuke , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Dohi Tomoharu , Nakatani Daisaku , Hikoso Shungo , Sakata Yasushi ,   Osaka CardioVascular Conference (OCVC)‐Heart Failure Investigators
Published: July 2021

Aims

At present, the clinical significance of admission hyperglycaemia in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. This study was designed to evaluate the relationship between admission hyperglycaemia and clinical outcome in HFpEF patients, especially in non‐diabetic patients.

Methods and results

We enrolled 486 non‐diabetic HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We divided non‐diabetic patients into two groups, an admission hyperglycaemia group whose blood glucose on admission was ≥7.0 mmol/L (148 patients) and a normoglycaemic group whose blood glucose on admission was <7.0 mmol/L (338 patients). The primary endpoint was all‐cause mortality, and the secondary endpoints were heart failure death and other causes of cardiac death. During a mean follow‐up period of 400 ± 335 days, all‐cause mortality was 69 patients. Twenty‐five patients suffered cardiac death. All‐cause mortality (P = 0.002), cardiac death (P = 0.009), and heart failure death (P = 0.001) were significantly more frequent in the admission hyperglycaemia group than in the normoglycaemic group. Admission hyperglycaemia was independently and significantly associated with all‐cause mortality and cardiac death (HR 2.01, 95% CI 1.20–3.34, P = 0.008 and HR 3.03, 95% CI 1.35–6.96, P = 0.007, respectively).

Conclusions

Non‐diabetic HFpEF patients with admission hyperglycaemia when hospitalized for heart failure had poorer clinical outcomes than normoglycaemic patients.
Ferric carboxymaltose for the treatment of iron deficiency in heart failure: a multinational cost‐effectiveness analysis utilising AFFIRM‐AHF
Authors: McEwan Phil , Ponikowski Piotr , Davis Jason A. , Rosano Giuseppe , Coats Andrew J.S. , Dorigotti Fabio , O'Sullivan Donal , Ramirez de Arellano Antonio , Jankowska Ewa A.
Published: July 2021

Aims

Iron deficiency is common in patients with heart failure (HF). In AFFIRM‐AHF, ferric carboxymaltose (FCM) reduced the risk of hospitalisations for HF (HHF) and improved quality of life vs. placebo in iron‐deficient patients with a recent episode of acute HF. The objective of this study was to estimate the cost‐effectiveness of FCM compared with placebo in iron‐deficient patients with left ventricular ejection fraction <50%, stabilised after an episode of acute HF, using data from the AFFIRM‐AHF trial from Italian, UK, US and Swiss payer perspectives.

Methods and results

A lifetime Markov model was built to characterise outcomes in patients according to the AFFIRM‐AHF trial. Health states were defined using the 12‐item Kansas City Cardiomyopathy Questionnaire (KCCQ‐12). Subsequent HHF were incorporated using a negative binomial regression model with cardiovascular and all‐cause mortality incorporated via parametric survival analysis. Direct healthcare costs (2020 GBP/USD/EUR/CHF) and utility values were sourced from published literature and AFFIRM‐AHF. Modelled outcomes indicated that treatment with FCM was dominant (cost saving with additional health gains) in the UK, USA and Switzerland, and highly cost‐effective in Italy [incremental cost‐effectiveness ratio (ICER) EUR 1269 per quality‐adjusted life‐year (QALY)]. Results were driven by reduced costs for HHF events combined with QALY gains of 0.43–0.44, attributable to increased time in higher KCCQ states (representing better functional outcomes). Sensitivity and subgroup analyses demonstrated data robustness, with the ICER remaining dominant or highly cost‐effective under a wide range of scenarios, including increasing treatment costs and various patient subgroups, despite a moderate increase in costs for de novo HF and smaller QALY gains for ischaemic aetiology.

Conclusion

Ferric carboxymaltose is estimated to be a highly cost‐effective treatment across countries (Italy, UK, USA and Switzerland) representing different healthcare systems.
Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care
Authors: Trevisan Marco , Fu Edouard L. , Xu Yang , Savarese Gianluigi , Dekker Friedo W. , Lund Lars H. , Clase Catherine M. , Sjölander Arvid , Carrero Juan J.
Published: July 2021

Aims

Whether to continue or stop mineralocorticoid receptor antagonists (MRA) after an episode of hyperkalaemia is a challenge in clinical practice. While stopping MRA may prevent recurrent hyperkalaemias, it deprives patients of their cardioprotection. We here assessed the association between stopping vs. continuing MRA therapy after hyperkalaemia and the subsequent risks of adverse health events.

Methods and results

Observational study from the Stockholm CREAtinine Measurements (SCREAM) project 2006–2018. We identified patients initiating MRA and surviving a first‐detected episode of hyperkalaemia (plasma potassium >5.0 mmol/L). Using target trial emulation methods, we assessed the association between stopping vs. continuing MRA within 6 months after hyperkalaemia and subsequent outcomes. The primary outcome was the composite of hospital admission with heart failure, stroke, myocardial infarction, or death. The secondary outcome was occurrence of another hyperkalaemia event. Among 39 518 patients initiating MRA, we identified 7366 who developed hyperkalaemia. Median age was 76 years, 45% were women and 69% had a history of heart failure. Following hyperkalaemia, 2222 (30%) discontinued treatment. Compared with continuing MRA, stopping therapy was associated with a lower 2‐year risk of recurrent hyperkalaemia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.72–0.79], but a higher risk of the primary outcome (HR 1.10, 95% CI 1.06–1.14). Similar results were observed in patients with heart failure, after censoring when treatment decision was changed, and across pre‐specified subgroups.

Conclusions

Stopping MRA after an episode of hyperkalaemia was associated with reduced risk for recurrent hyperkalaemia, but higher risk of death or cardiovascular events. Recurrent hyperkalaemia was common in either strategy.
Post‐discharge arrhythmic risk stratification of patients with acute myocarditis and life‐threatening ventricular tachyarrhythmias
Authors: Gentile Piero , Merlo Marco , Peretto Giovanni , Ammirati Enrico , Sala Simone , Della Bella Paolo , Aquaro Giovanni Donato , Imazio Massimo , Potena Luciano , Campodonico Jeness , Foà Alberto , Raafs Anne , Hazebroek Mark , Brambatti Michela , Cercek Andreja Cerne , Nucifora Gaetano , Shrivastava Sanskriti , Huang Florent , Schmidt Matthieu , Muser Daniele , Van de Heyning Caroline M. , Van Craenenbroeck Emeline , Aoki Tatsuo , Sugimura Koichiro , Shimokawa Hiroaki , Cannatà Antonio , Artico Jessica , Porcari Aldostefano , Colopi Marzia , Perkan Andrea , Bussani Rossana , Barbati Giulia , Garascia Andrea , Cipriani Manlio , Agostoni Piergiuseppe , Pereira Naveen , Heymans Stephane , Adler Eric D. , Camici Paolo Guido , Frigerio Maria , Sinagra Gianfranco
Published: July 2021

Aims

The outcomes of patients presenting with acute myocarditis and life‐threatening ventricular arrhythmias (LT‐VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population.

Methods and results

We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT‐VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter‐defibrillator therapy or synchronized external cardioversion. Median follow‐up was 23 months [first to third quartile (Q1–Q3) 7–60]. Fifty‐eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1–Q3 2.5–24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38–6.11]; late gadolinium enhancement involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39–8.53), and absence of positive short‐tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40–4.79) at first CMR.

Conclusions

Among patients discharged with a diagnosis of myocarditis and LT‐VA, 37.2% had recurrences of MAEs during follow‐up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.
Nickel Complexes and Carbon Dots for Efficient Light‐Driven Hydrogen Production
Authors: Ladomenou Kalliopi , Papadakis Michael , Landrou Georgios , Giorgi Michel , Drivas Charalambos , Kennou Stella , Hardré Renaud , Massin Julien , Coutsolelos Athanassios G. , Orio Maylis
Published: July 2021

Nitrogen‐doped carbon dots were used as photosensitizers for H2 evolution in the presence of a series of mononuclear thiosemicarbazone nickel complexes. The catalysts were designed to display different substituents at the para position of the phenyl rings. These chemical modifications tune the electron‐donating abilities of the complexes and influence their capability to reduce protons into hydrogen. All photocatalytic experiments were performed in aqueous solution, using as sacrificial electron donor TCEP/Asc (1 : 1), 0.1 M each, at pH=5. The complex bearing the most electron‐donating ligand with the dimethylamino (N(CH3)2) substituent behaves as the best catalyst in our series of photocatalytic systems with TONCAT=148, under white led radiation for 30 h. Therefore, this noble metal‐free system can effectively produce hydrogen in water and further chemical modification of the ligand will likely improve its production.
Photoredox Dual Catalysis: A Fertile Playground for the Discovery of New Reactivities
Authors: Mastandrea Marco M. , Pericàs Miquel A.
Published: July 2021

The last fifteen years have witnessed the advent of photoredox catalysis as a powerful tool for the generation of radical species under mild, controlled conditions. The exploitation of visible light as a sustainable and cheap source of energy has enabled the resurgence of classical radical chemistry as well as the discovery of several new transformations. At the same time, many research groups have demonstrated the easy implementation of dual catalytic protocols, further extending the range of accessible reactivities. In particular, the merging of photoredox and organocatalysis has allowed to involve radical species in asymmetric transformations, while metallaphotoredox has given access to odd‐electron reactivity in transition metal catalysis. In this minireview, after a quick look at the basic principles of photoredox catalysis, we will describe the seminal works of the field furnishing a focus on the proposed reaction mechanism.
Metallophilic Interactions in Bimetallic Cyclometalated Platinum(II) N‐Heterocyclic Carbene Complexes
Authors: Pinter Piermaria , Soellner Johannes , Strassner Thomas
Published: July 2021

Platinum(II) complexes with rigid and electron donating ligands are efficient phosphorescent emitters at room temperature. However, the excited‐state lifetimes of these complexes are, in general, relatively long. This problem, which can result in the degradation of the emitter, can be overcome by exploiting the natural tendency of platinum to form metallophilic interactions and aggregates. Herein, we report platinum(II) bimetallic complexes with 100 % quantum yield and at the same time exceptionally short radiative decay times, which in some cases are up to a hundredfold faster than the analogous monometallic complexes.
Iron‐Catalyzed Synthesis of Pyrrole Derivatives and Related Five‐Membered Azacycles
Authors: Wang Yeming , Zhang Chaoqun , Li Shizhe , Liu Lihui
Published: July 2021

Pyrrole derivatives and their related five‐membered azacycles are a class of important five‐membered aromatic nitrogen heterocyclic compounds, and their synthesis attracted much the attention of organic chemists. Iron catalysis has been widely used in various organic transformations owing to their excellent catalytic activity, environmentally benign character, easy accessibility and low price. Over the past decades, a variety of facile and effective syntheses of pyrrole derivatives and related five‐membered azacycles based on iron catalysis has been reported. In this Minireview, the development of the iron‐catalyzed synthesis of pyrrole derivatives and their related five membered azacycles is reported in a comprehensive way, covering the literature up to March 2021.
Effects of childhood trauma on pain‐related distress in adults
Authors: Walton Dave Mark , Tremblay Paul , Seo Wonjin , Elliott James Matthew , Ghodrati Maryam , May Curtis , MacDermid Joy Christine
Published: July 2021

Background

Much of the work in post‐musculoskeletal (MSK) trauma and distress has been conducted through frameworks that start from the injury and go forward to better understand the trajectories and predictors of recovery. However, stress–diatheses models suggest that reactions to trauma are shaped by pre‐existing experiences of the person more than the parameters of the event itself. In this study, we explore the effects of adverse childhood experiences (ACEs) on traumatic threat appraisal, distress and pain‐related functional interference in adulthood.

Methods

Adult participants with acute, non‐catastrophic musculoskeletal trauma completed a battery of questionnaires that included the Adverse Childhood Experiences Questionnaire (ACEQ), the Brief Illness Perceptions Questionnaire (BIPQ), the Traumatic Injuries Distress Scale (TIDS) and the Brief Pain Inventory (BPI). An a priori model was evaluated through path analysis to determine the variance in BPI Interference scores explained through direct or indirect pathways between these variables (ACEQ‐>BIPQ, BIPQ‐>TIDS, TIDS‐>BPI). The analysis was repeated for the sample when disaggregated by sex.

Results

In n = 114, the base model was saturated. After removing non‐significant pathways, the ACEQ‐>BIPQ‐>TIDS‐>BPI paths were significant and in the expected direction, explaining 57.1% of variance in acute BPI Interference score. When disaggregated by sex, the effect of ACEs on threat appraisal was only significant in men and not women, although this analysis was exploratory.

Conclusions

Acute pain‐related interference could be predicted by post‐traumatic distress and threat appraisal. Threat appraisal could be further predicted through ACEs, more childhood adversities were associated with more threatening appraisal of trauma in adulthood. The disaggregated finding that the effects of childhood adversities were only significant in males requires further exploration.

Significance

This study explores the potential pathways of the stress–diathesis model while focusing on adverse childhood experiences as a novel contribution to the field of acute post‐trauma pain. The findings may inform future research design and interpretation of acute‐to‐chronic pain risk stratification tools.
Recent advances in magnetic digital microfluidic platforms
Authors: Cheng Hao , Liu Hangrui , Li Weihua , Li Ming
Published: July 2021

Magnetic Digital microfluidics (DMF), which enables the manipulation of droplets containing different types of samples and reagents by permanent magnets or electromagnet arrays, has been used as a promising platform technology for bioanalytical and preparative assays. This is due to its unique advantages such as simple and “power free” operation, easy assembly, great compatibility with auto control systems, and dual functionality of magnetic particles (actuation and target attachment). Over the past decades, magnetic DMF technique has gained a widespread attention in many fields such as sample‐to‐answer molecular diagnostics, immunoassays, cell assays, on‐demand chemical synthesis, and single‐cell manipulation. In the first part of this review, we summarised features of magnetic DMF. Then, we introduced the actuation mechanisms and fabrication of magnetic DMF. Furthermore, we discussed five main applications of magnetic DMF, namely drug screening, protein assays, polymerase chain reaction (PCR), cell manipulation, and chemical analysis and synthesis. In the last part of the review, current challenges and limitations with magnetic DMF technique were discussed, such as biocompatibility, automation of microdroplet control systems, and microdroplet evaporation, with an eye on towards future development.
Identification of Three Coexistent Defect Types in Hematite Photoanodes through Structure–Property Analysis
Authors: Zhang Jixi , Liu Yutong , Smith Rodney D. L.
Published: July 2021

Structural defects present in hematite photoanodes are analyzed by correlating parameters derived from Raman spectra, band structure measurements and photoelectrochemical (PEC) oxygen evolution reaction performance. A series of photoanodes with varying quality of hematite are prepared by sintering akaganeite films with a systematically varied protocol. Data acquired through Raman microscopy, linear sweep voltammetry, and electrochemical impedance spectroscopy is parametrized and systematically compared to detect relationships amongst the data. Correlations between the structural information contained within the Raman spectra and PEC parameters enable the identification of three types of structural defects within the material. Each defect type is found to exert unique influence on PEC behavior and each became dominant under specific fabrication conditions. A straightforward approach to detecting defects in photoelectrodes and identifying their influence on photoelectrode properties and behavior is provided.
Continuous Processing of Cathode Slurry by Extrusion for Lithium‐Ion Batteries
Authors: Haarmann Matthias , Grießl Desiree , Kwade Arno
Published: July 2021

In this work, detailed investigations concerning a continuous mixing process for lithium‐ion battery (LIB) electrodes are conducted. NCM622 (Li(Ni0.6Co0.2Mn0.2)O2) cathode electrodes are fabricated on behalf of a corotating twin screw extruder. Studies are performed concerning different material compositions and processing parameters, such as screw speed. Processing routes in relation to feeding of binder to the process zones as a dry powder or presolved in a liquid are examined. The produced cathode slurries are analyzed concerning rheological properties and dispersing degree, meaning particle size distribution. Subsequently, the coated electrodes are characterized regarding electrical conductivity, mechanical properties, and pore size distribution. Up to the present, the continuous mixing process of LIB electrodes is barely investigated. This study provides deep insight into the process–structure–property relations of the continuous mixing process.
Sunroot snack bar: Optimization, characterization, consumer perception, and storage stability assessment
Authors: Abedelmaksoud Tarek Gamal , Smuda Sayed Saad , Altemimi Ammar B. , Mohamed Reda Mahgoub , Pratap‐Singh Anubhav , Ali Marwa Rashad
Published: July 2021

This study reports the evolution of phenolics, inulin content, proximate composition, hardness, and sensory characteristics of an inulin‐rich healthy snack bar (The Sunroot Snack Bar) over 90 days of storage in refrigerated and room temperature storage. A response surface methodology (RSM) with a central composite rotatable design was first employed for optimizing the concentrations of sunroot, potato, and oats. The optimum selected concentrations of sunroot, potato, and oat were 53.99, 37.88, and 5 g, respectively, and a quadratic model was found to yield the best fit. Analysis of variance revealed that a higher sunroot content resulted in more firmness of the bar and higher overall acceptability in sensory trials. Sunroot snack bar samples without flavor (control), sunroot snack bar with cheese flavor (S1), and sunroot snack bar with olive flavor (S2) were then tested for sensory, chemical, phytochemicals, and microbial contents among control, S1, and S2 samples over a 90‐day shelf‐life study. Results showed no significant (p < .05) changes in these contents on addition of flavor. An increase in microbial load and the appearance of a bitter taste after 30 days of fresh sunroot storage were observed. No microbial growth was observed in all sunroot snack bar samples during storage at 4°C, while some microbial growth was observed at 25°C for 90 days. It was inferred that the high‐quality shelf life of the sunroot bar was 90 days at 4°C, which was shortened to a month if the bars were preserved at 25°C. There was a significant phenolic and inulin content loss at 25°C compared with 4°C in total phenolic component. Based on the results of sensory evaluation, online questionnaire of customer experience, and cost analysis, this study successfully used sunroot tubers for the production of snack bars as a promising new raw material, which was introduced healthily with a suitable price for such product compared with other products in the market.
Rational repricing of risk during COVID‐19: Evidence from Indian single stock options market
Authors: Agarwalla Sobhesh Kumar , Varma Jayanth R. , Virmani Vineet
Published: July 2021

Could the COVID‐19 related market crash and subsequent rebound be explained as a rational response to evolving conditions? Our results using multiple forward‐looking measures of uncertainty implied from stock option prices suggest so. First, we find a gradual build‐up of volatility during the month preceding the spike at the start of the pandemic. Second, while tail risk declined after government interventions, the level of uncertainty remained elevated for stocks across industries. Third, the dynamics of decline in tail risk in stocks was industry‐dependent, suggesting that the market performed a fine‐grained analysis of each stock's uncertainty through the pandemic.
Heterogeneous outer‐rise seismicity within the Izu–Bonin subduction zone and its tectonic implications
Authors: Gong Wei , Jiang Xiaodian , Xing Junhui , Xu Chong , Zhang Hao , An Long , Li Chaoyang
Published: July 2021

Combining with available focal mechanisms, we chose 13 events (M ≥ 3.5) for waveform inversion to determine the stress field at the outer‐rise region within the Izu–Bonin subduction zone. Indicated by the distribution of the epicentres, seismic energy release, and stress field within the outer‐rise region, the subduction zone is divided into three segments separated by 29°N and 32.5°N. The outer‐rise seismicity presents an extensional stress field in the upper part (0–40 km) of the subducting oceanic plate. Whereas, the maximum focal depth within the outer‐rise region tends to increase northwards, and the deep part (>40 km) of the subducting slab is gradually governed by a general compressional stress regime that has never been observed before, which implies that the subduction of the old Pacific Plate along the Izu–Bonin trench is characterized by a heterogeneous bending deformation. According to modelling the flexural bending of the oceanic lithosphere, it is observed that effective elastic thickness (Te) of the Izu–Bonin subduction zone decreases from 38 to 28 km along the trench strike, indicating a decrease of plate rigidity northwards. The spatial variations of Te exactly explain the heterogeneous outer‐rise seismicity within the Izu–Bonin subduction zone, which is the energy release of the bending formation of the subducting plate. As shown in the results presented here, the varied flexural deformation of the subducting Pacific Plate is closely correlated with the heterogeneous thermal age, the varied morphology, and the coupling degree of the subducting plate.
Enhancing Linkage to Hepatitis C Virus Treatment Following Pregnancy in Women Identified During Perinatal Care
Authors: Epstein Rachel L. , Moloney Carole , Garfinkel Jacob , Saia Kelley , Wachman Elisha M. , Lodi Sara , Pelton Stephen I.
Published: July 2021

Amid the current US opioid crisis, hepatitis C virus (HCV) infection rates continue to rise in young adults, including among pregnant women, yet few studies describe linkage to care and treatment in pregnant or postpartum women with HCV infection. We used electronic health record data to estimate HCV treatment rates for postpartum women before (January 2014‐September 2016) and during (October 2016‐March 2018) implementation of a maternal–infant HCV linkage program in combination with a multidisciplinary clinic to colocate mother and infant care. Using Poisson regression models, we compared HCV treatment initiation rates, adjusting for demographics, substance use, and treatment. From January 2014 through March 2018, 343 women who were HCV seropositive delivered at our institution. Of these, 95% completed HCV nucleic acid testing and 255 women had chronic HCV infection. Mean age was 30 years, 96% were publicly insured, and 94% had documented substance use. HCV treatment initiation increased from 28/164 (17.1%) women with chronic HCV infection in the preintervention period to 16/66 (24.2%) with the linkage‐only intervention and 13/25 (52.0%) with the linkage intervention and colocated care. Adjusted analyses demonstrated that women delivering during the intervention period initiated HCV treatment at 2.40 times (95% confidence interval [CI], 1.10‐5.25; linkage only) and 3.36 times (95% CI, 1.57‐7.17; linkage and colocated care) the rate of women delivering preintervention. Women on buprenorphine had higher HCV treatment initiation rates compared with those on methadone (rate ratio, 2.10; 95% CI, 1.05‐4.21). Conclusion: HCV linkage to care and treatment rates improved in the setting of mother–infant linkage and colocated care interventions. Perinatal care may represent a critical venue to identify, link, and treat women for HCV infection to improve their own health and prevent transmission to subsequent pregnancies.
Meta‐analysis and Consolidation of Farnesoid X Receptor Chromatin Immunoprecipitation Sequencing Data Across Different Species and Conditions
Authors: Jungwirth Emilian , Panzitt Katrin , Marschall Hanns‐Ulrich , Thallinger Gerhard G. , Wagner Martin
Published: July 2021

Farnesoid X receptor (FXR) is a nuclear receptor that controls gene regulation of different metabolic pathways and represents an upcoming drug target for various liver diseases. Several data sets on genome‐wide FXR binding in different species and conditions exist. We have previously reported that these data sets are heterogeneous and do not cover the full spectrum of potential FXR binding sites. Here, we report the first meta‐analysis of all publicly available FXR chromatin immunoprecipitation sequencing (ChIP‐seq) data sets from mouse, rat, and human across different conditions using a newly generated analysis pipeline. All publicly available single data sets were biocurated in a standardized manner and compared on every relevant level from raw reads to affected functional pathways. Individual murine data sets were then virtually merged into a single unique “FXR binding atlas” spanning all potential binding sites across various conditions. Comparison of the single biocurated data sets showed that the overlap of FXR binding sites between different species is modest and ranges from 48% (mouse‐human) to 55% (mouse‐rat). Moreover, in vivo data among different species are more similar than human in vivo data compared to human in vitro data. The consolidated murine global FXR binding atlas virtually increases sequencing depth and allows recovering more and novel potential binding sites and signaling pathways that were missed in the individual data sets. The FXR binding atlas is publicly searchable (https://fxratlas.tugraz.at). Conclusion: Published single FXR ChIP‐seq data sets and large‐scale integrated omics data sets do not cover the full spectrum of FXR binding. Combining different individual data sets and creating an “FXR super‐binding atlas” enhances understanding of FXR signaling capacities across different conditions. This is important when considering the potential wide spectrum for drugs targeting FXR in liver diseases.
Measuring catastrophe in paying for healthcare: A comparative methodological approach by using National Sample Survey, India
Authors: Dwivedi Rinshu , Pradhan Jalandhar , Athe Ramesh
Published: July 2021

Healthcare expenditure significantly varies among various segments of the population. The appropriate measures of catastrophic health expenditure (CHE) will help to unravel the real burden of spending among households. Present study provides a link between the theoretical insights from Grossman's model and various methodological approaches for the estimation of CHE by using data from the three rounds of nationally representative Consumer Expenditure Surveys, India. Statistical analysis has been carried out by using multivariate logistic regression to identify the major determinants of CHE. Findings indicate that the occurrence of CHE has increased during 1993–2012. Rural residents and households with varying age composition such as with higher numbers of children and elderly were at higher risk. Economic status is significantly associated with CHE and increased demand for healthcare. The measurements differ as per the methodological approaches of CHE and definition of household's capacity to pay. Approach‐based variations in the results can be of key importance in determining trends and magnitude in CHE. Despite these variations in measurements, study finds a limited incidence of CHE among the disadvantaged segment of the population though a greater share was devoted to health expenditure in recent years. Better risk pooling mechanism is required to address the healthcare needs of the disadvantaged segment such as elderly, children, poor and rural population in India.
Nonsimilar boundary layer flow of Cross fluid induced by a heated stretched sheet
Authors: Shehzad Sabir A. , Ahmed Maria , Rauf Amar
Published: July 2021

This paper deals with the nonisothermal boundary layer flow of Cross fluid due to a stretching sheet. Unlike previous studies on boundary layer flow of Cross fluid, a nonsimilar formulation is adopted to transform the boundary layer equations into nondimensional form. The problem is characterized by three dimensionless parameters, namely, the Deborah number, the Prandtl number, and dimensionless distance along the sheet. The transformed equations are simulated by a numerical scheme with the help of MAPLE software. The velocity and temperature profiles inside the boundary layer are calculated and shown graphically. The skin friction coefficient and Nusselt number at various axial stations are also tabulated for several values of Deborah number and Prandtl number.
Machine learning‐based tri‐stage classification of Alzheimer's progressive neurodegenerative disease usingPCAandmRMRadministered textural, orientational, and spatial features
Authors: Karim Razaul , Shahrior Ashef , Rahman Mohammad Motiur
Published: July 2021

Alzheimer's disease is a subject of substantial concern with ample scope for novel discoveries in the field of modern computational medical study for its reputation of being one of the most exorbitant and life‐threatening neurodegenerative diseases of the current age. The prime objective of this research is to develop a system that can automatically detect three stages of Alzheimer's disease—Alzheimer's dementia, mild cognitive impairment, and cognitively normal using the traditional machine learning approaches. The dataset collected from Alzheimer's Disease Neuroimaging Initiative containing three types of data as mentioned above with labeled images is used throughout the research. In the proposed method, contrast limited adaptive histogram equalization handles the qualitative visual distortion in advance of feature calculation. Three distinct types of features are identified from structural MR images such as textural, orientational, and spatial features as the gray‐level co‐occurrence matrix, histogram of oriented gradients, and vector of locally aggregated descriptors. Apart from this, principal component analysis and minimum redundancy maximum relevance operate on the generated feature set for dimensionality reduction and to confer a comparative perspective as well. Experiments conducted upon the availed dataset exhibit that the proposed methodology outperforms other noteworthy existing methods for multiclass detection of Alzheimer's disease achieving accuracy ranging from 94% to 97% with respect to the feature set and models in action. Moreover, a significant outcome is found after applying the findings to a new independent test dataset from the same data source.
First‐principles based theoretical investigation of impact of polyolefin structure on photooxidation behavior
Authors: Khatri Vikas , Dhattarwal Harender S. , Kashyap Hemant K. , Singh Gurmeet
Published: July 2021

Despite their mass production and large applications, polyolefins' stability and durability toward the air, moisture, and weather resistance is a challenge for the ecosystem. After long‐term exposure to ultraviolet (UV) radiation or high‐temperature or erosion, polyolefins undergo degradation generating microplastics (MPs). The MPs generated after the degradation of these polyolefins are hazardous for the ecosystem. In the present work, we have carried out density functional theory (DFT) studies to investigate the photodegradation of six different polyolefins ranging from polyethylene to polydecene, differing in side‐chain. Herein, we have investigated photooxidized derivatives of different polyolefins and analyzed their relative stability, conformations, UV–visible spectral behavior, and carbonyl index. The photooxidized derivatives of various polyolefins formed during degradation are examined. The time‐dependent density functional theory analysis confirms that the carbonyl groups of photooxidized products show absorption peak in Infrared (IR) and visible region, acting as light‐absorbing species. The relative stabilities of hydroperoxide formed during photo/thermal oxidation of different polyolefins have been evaluated to explain the degradation behavior. The oligomerization and stabilization energies of their corresponding hydroperoxide's were computed and analyzed to explain the degradation behavior of the polyolefins. The computed results suggest that polyolefins in their pristine state are stable toward photooxidation, but chemical impurities like carbonyl, unsaturated carbonyl, carboxylic acid, and hydroperoxide derivatives make them prone to undergo degradation, a fundamental process leading to generation of MPs. The comparative results confirmed that the side‐chain length affects the stability and degradation of different polyolefins toward photooxidation.
A quantitative structure–activity relationship study on CXL017 derivatives as effective drugs for cancer treatment
Authors: Nekoei Mehdi , Mohammadhosseini Majid , Pourbasheer Eslam
Published: July 2021

A novel quantitative structure–activity relationship study was established on a set of ethyl‐2‐amino‐6‐(3.5‐dimethoxyphenyl)‐4‐(2‐ethoxy‐2‐oxoethyl)‐4H‐chromene‐3 carboxylate (CXL017) derivatives to predict their half‐maximal inhibitory concentration (IC50) values. A principal component analysis pattern was first used to divide the whole data set into training and test sets. Then, stepwise (SW) and genetic algorithm (GA) feature selection approaches were selected to choose the proper molecular descriptors which were then subjected to multiple linear regression (MLR). Accordingly, linear models consisting of seven and six molecular descriptors were constructed and their stability was further checked using leave‐one‐out (LOO) and leave group out (LGO) cross‐validation techniques. In addition, the 15 compounds of the test set were further directed to external statistical validation to assess the forecasting capability of the generated models. A simple comparison of the results obtained by the two methodologies showed that the GA‐MLR model had some superiorities versus the SW‐MLR modeling approach, for example, R2train = 0.832, R2test = 0.816, Q2LOO = 0.788 and Q2LGO = 0.796, Ftrain = 44.01, Ftest = 6.67, MSEtrain = 0.069, MSEtest = 0.053 for the computation of the relevant IC50 values. Based on the information derived from the generated models, some key features are identifiable to appraise the activity of the organic drugs that can be used to design new anticancer agents.
Assessment of the knowledge and awareness of pediatric residents and pediatricians about autism spectrum disorder at a single center in Turkey
Authors: Çitil Gülce , Çöp Esra , Açıkel Sadettin Burak , Sarı Eyüp , Karacan Can Demir , Şenel Saliha
Published: July 2021

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder and pediatricians play a critical role in early diagnosis. This study was conducted to evaluate the knowledge, beliefs, and experiences of pediatric residents and pediatricians about ASD. A 35‐item questionnaire consisting of two sections was administered. The diagnostic features section consisted of questions measuring the level of knowledge about diagnostic criteria of ASD. The general knowledge and beliefs section consisted of questions about beliefs and experiences regarding ASD. The study consisted of 101 participants. Mean score obtained by all participants from the diagnostic features section was 5.78 ± 1.65. The mean scores obtained by residents and pediatricians from the diagnostic features section were 5.35 ± 1.5 and 6.31 ± 1.68. Pediatricians obtained higher scores significantly than residents from diagnostic features section (t = −2.99, p = 0.004). The mean scores obtained by residents and pediatricians from section of general knowledge and beliefs were 13.69 ± 3 and 14.48 ± 3.15. This difference was not significant (t = −1.27, p = 0.225). This study suggests that participants' knowledge and awareness about ASD was insufficient and while pediatricians knew more about the diagnostic criteria, their awareness and approach regarding ASD were no different from pediatric residents in general practice.
How do peer support workers value self‐directed growth over conventional change goals among young people experiencing homelessness?
Authors: Erangey James , Marvin Connor , Littman Danielle M. , Bender Kim , Mollica Meredith , Milligan Tara , Lucas Tom
Published: July 2021

The aim of this study is to explore how peer support workers (individuals with similar lived experiences employed to provide support) conceptualize change work with young people experiencing homelessness. The present study used participatory qualitative methods, including semistructured interviews and journaling with peer support workers and program supervisors and administrators, to understand how peers understand change work with young people experiencing homelessness. This study found that peers center self‐directed growth among young people experiencing homelessness, rather than change that prioritizes meeting program‐directed outcomes such as obtaining housing or gaining employment. Peer relationships invite possibility and create containers of hope when supporting young people experiencing homelessness, regardless of their paths. Lastly, peers recognize that growth happens in seasons, and embrace such seasons as checkpoints on youths' journeys. Such findings may guide service providers beginning peer programming or those considering models for engaging young people experiencing homelessness in relationship‐supported growth.
1,25‐Dihydroxyvitamin D3 and dietary vitamin D reduce inflammation in mice lacking intestinal epithelial cell Rab11a
Authors: Goswami Sayantani , Flores Juan , Balasubramanian Iyshwarya , Bandyopadhyay Sheila , Joseph Ivor , Bianchi‐Smak Jared , Dhawan Puneet , Mücahit Derya M. , Yu Shiyan , Christakos Sylvia , Gao Nan
Published: July 2021

A number of studies have examined the effects of 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) on intestinal inflammation driven by immune cells, while little information is currently available about its impact on inflammation caused by intestinal epithelial cell (IEC) defects. Mice lacking IEC‐specific Rab11a a recycling endosome small GTPase resulted in increased epithelial cell production of inflammatory cytokines, notably IL‐6 and early onset of enteritis. To determine whether vitamin D supplementation may benefit hosts with epithelial cell‐originated mucosal inflammation, we evaluated in vivo effects of injected 1,25(OH)2D3 or dietary supplement of a high dose of vitamin D on the gut phenotypes of IEC‐specific Rab11a knockout mice (Rab11aΔIEC). 1,25(OH)2D3 administered at 25 ng, two doses per mouse, by intraperitoneal injection, reduced inflammatory cytokine production in knockout mice compared to vehicle‐injected mice. Remarkably, feeding mice with dietary vitamin D supplementation at 20,000 IU/kg spanning fetal and postnatal developmental stages led to improved bodyweights, reduced immune cell infiltration, and decreased inflammatory cytokines. We found that these vitamin D effects were accompanied by decreased NF‐κB (p65) in the knockout intestinal epithelia, reduced tissue‐resident macrophages, and partial restoration of epithelial morphology. Our study suggests that dietary vitamin D supplementation may prevent and limit intestinal inflammation in hosts with high susceptibility to chronic inflammation.
DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fibroblasts
Authors: Han Chien‐Kuo , Lee Wei‐Fang , Hsu Chin‐Jung , Huang Yuan‐Li , Lin Chih‐Yang , Tsai Chun‐Hao , Huang Chien‐Chung , Fong Yi‐Chin , Wu Min‐Huan , Liu Ju‐Fang , Tang Chih‐Hsin
Published: July 2021

Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by increasing levels of proinflammatory cytokines. The ubiquitous enzyme dipeptidyl peptidase‐4 (DPP4, also known as CD26) regulates different immune disorders, although the effects of DPP4 in RA are uncertain. Here, we found lower levels of DPP4 in RA synovial tissues compared with normal tissues. DPP4 levels were also lower in a rat collagen‐induced arthritis model than in control (healthy) rats. Overexpression of DPP4 or exogenous treatment of RA synovial fibroblasts with DPP4 reduced levels of proinflammatory interleukin (IL)‐1β, IL‐6, and IL‐13, and increased anti‐inflammatory IL‐10 synthesis, while DPP4 inhibitors sitagliptin and vildagliptin increased proinflammatory cytokine production, indicating an enhanced risk of RA development. The evidence suggests that increasing DPP4 expression is a novel strategy for RA disease.
Meta‐analysis of genome‐wide DNA methylation and integrative omics of age in human skeletal muscle
Authors: Voisin Sarah , Jacques Macsue , Landen Shanie , Harvey Nicholas R. , Haupt Larisa M. , Griffiths Lyn R. , Gancheva Sofiya , Ouni Meriem , Jähnert Markus , Ashton Kevin J. , Coffey Vernon G. , Thompson Jamie‐Lee M. , Doering Thomas M. , Gabory Anne , Junien Claudine , Caiazzo Robert , Verkindt Hélène , Raverdy Violetta , Pattou François , Froguel Philippe , Craig Jeffrey M. , Blocquiaux Sara , Thomis Martine , Sharples Adam P. , Schürmann Annette , Roden Michael , Horvath Steve , Eynon Nir
Published: July 2021

Background

Knowledge of age‐related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.

Methods

We conducted a large‐scale epigenome‐wide association study meta‐analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18–89 years old). We explored the genomic context of age‐related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age‐related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).

Results

We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age‐related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.

Conclusions

We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open‐access, user‐friendly, web‐based tool called MetaMeth (https://sarah‐voisin.shinyapps.io/MetaMeth/).
Inhibition of circ_0081234 reduces prostate cancer tumor growth and metastasis via the miR‐1/MAP 3 K1 axis
Authors: Zhang Guangyao , Liu Yibin , Yang Jianhui , Wang Haiming , Xing Zhengwei
Published: July 2021

Introduction

Circular RNAs (circRNAs) are crucial regulators of tumor occurrence and progression, and circRNAs are enriched and stable in exosomes. The present study aimed to explore the role and potential mechanism of cancer‐derived exosomal circ_0081234 in prostate cancer (PCa).

Methods

Exosomes were extracted using the ExoQuick Precipitation Kit (System Biosciences, Mountain View, CA, USA). The levels of circ_0081234, miR‐1 and mitogen‐activated protein kinase kinase kinase 1 (MAP 3 K1) were examined using a quantitative real‐time polymerase chain reaction or western blotting. Cell migration and invasion were evaluated via a transwell assay. The protein levels of N‐cadherin, vimentin and E‐cadherin were detected by western blotting. The interaction between miR‐1 and circ_0081234 or MAP 3 K1 was verified via a dual‐luciferase reporter assay and an RNA pull‐down assay.

Results

The circ_0081234 level was increased in PCa tissues with spinal metastasis in comparison to primary PCa tissues without spinal metastasis. Exosomal circ_0081234 promoted the migration, invasion and epithelial–mesenchymal transition of PCa cells. Knockdown of circ_0081234 blocked PCa cell progression by regulating miR‐1. In addition, miR‐1 overexpression suppressed PCa cell progression by repressing MAP 3 K1. Moreover, circ_0081234 increased MAP 3 K1 level via sponging miR‐1. Depletion of circ_0081234 inhibited tumor growth in vivo.

Conclusions

Exosomal circ_0081234 promoted migration, invasion and epithelial–mesenchymal transition of PCa cells by regulating the miR‐1/MAP 3 K1 axis.