bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Hepatocyte Autophagy Leads to Synergistic IL‐1β and TNF Mouse Liver Injury and Inflammation
Authors: Shen Yang , Malik Shoaib Ahmad , Amir Muhammad , Kumar Pradeep , Cingolani Francesca , Wen Jing , Liu Yunshan , Zhao Enpeng , Farris Alton B. , Raeman Reben , Czaja Mark J. 
Published: February 2020

Background and Aims
The proinflammatory cytokine IL‐1β has been implicated in the pathophysiology of nonalcoholic and alcoholic steatohepatitis. How IL‐1β promotes liver injury in these diseases is unclear, as no IL‐1β receptor‐linked death pathway has been identified. Autophagy functions in hepatocyte resistance to injury and death, and findings of decreased hepatic autophagy in many liver diseases suggest a role for impaired autophagy in disease pathogenesis. Recent findings that autophagy blocks mouse liver injury from lipopolysaccharide led to an examination of autophagy’s function in hepatotoxicity from proinflammatory cytokines.

Approach and Results
AML12 cells with decreased autophagy from a lentiviral autophagy‐related 5 (Atg5) knockdown were resistant to toxicity from TNF, but sensitized to death from IL‐1β, which was markedly amplified by TNF co‐treatment. IL‐1β/TNF death was necrosis by trypan blue and propidium iodide positivity, absence of mitochondrial death pathway and caspase activation, and failure of a caspase inhibitor or necrostatin‐1s to prevent death. IL‐1β/TNF depleted autophagy‐deficient cells of ATP, and ATP depletion and cell death were prevented by supplementation with the energy substrate pyruvate or oleate. Pharmacological inhibitors and genetic knockdown studies demonstrated that IL‐1β/TNF‐induced necrosis resulted from lysosomal permeabilization and release of cathepsins B and L in autophagy‐deficient cells. Mice with a tamoxifen‐inducible, hepatocyte‐specific Atg5 knockout were similarly sensitized to cathepsin‐dependent hepatocellular injury and death from IL‐1β/TNF in combination, but neither IL‐1β nor TNF alone. Knockout mice had increased hepatic inflammation, and IL‐1β/TNF‐treated, autophagy‐deficient AML12 cells secreted exosomes with proinflammatory damage–associated molecular patterns.

Conclusions
The findings delineate mechanisms by which decreased hepatocyte autophagy promotes IL‐1β/TNF‐induced necrosis from impaired energy homeostasis and lysosomal permeabilization and inflammation through the secretion of exosomal damage–associated molecular patterns.
Investigation of the influence of various numbers of impeller blades on internal flow field analysis and the pressure pulsation of an axial pump based on transient flow behavior
Authors: Al‐Obaidi Ahmed Ramadhan 
Published: February 2020

AbstractIn the current study, the flow behavior in an axial pump through changing the number of impeller blades is analyzed. Due to the number of blades being very important geometrical parameters in the pump, the study of the influence of various numbers of blades on flow and pressure pulsation in the pump is carried out using the computational fluid dynamics technique. The sliding mesh with the standard turbulence k‐ε model is used to investigate the unsteady flow with several flows and impeller blades. Pump performance prediction results with available experimental data indicate reasonable and good agreement with each other. Static pressure, shear stress, and different velocity compounds are qualitatively analyzed. Moreover, the fluctuation pressure and average pressure under different operating conditions and impeller blades are quantitatively investigated. The numerical results show that the impeller blade has a high impact on pressure, shear stress, magnitude velocity, axial velocity, radial velocity, tangential velocity, and average pressure. Furthermore, this numerical study provides good and useful information for the hydraulic design of axial pumps.
The prospective curative role of lipoxin A4 in induced gastric ulcer in rats: Possible involvement of mitochondrial dynamics signaling pathway
Authors: Madi Nermin M. , Ibrahim Rowida R. , Alghazaly Ghada M. , Marea Karima E. , El‐Saka Mervat H. 
Published: February 2020

AbstractThis study purposed to examine the prospective curative role of lipoxin A4 (LXA4) in induced gastric ulcer in rats and explore the possible involvement of mitochondrial dynamics signaling pathway. Forty‐eight male Wistar rats were divided into four groups: control, indomethacin (IND), IND + omeprazole (IND + Omez), and IND+ LXA4 groups. At the end of the experiment, the gastric pH, gastric fluid volume, total gastric acidity, ulcer index, and curative index were estimated. The gene expression of mitochondrial related protein 1 and mitofusin 2 were determined. In addition, some mitochondrial parameters include mitochondrial transmembrane potential, complex‐I activity and reactive oxygen species were measured. Also, some gastric biochemical parameters, histopathological, and immunohistochemical analyses of the gastric mucosa were determined. We found that IND induced gastric ulcer, as manifested by the biochemical, histopathological, and immunohistochemical analyses. Both Omez and LXA4 treatment for 15 days alleviated the IND‐induced gastric ulcer as explored by ameliorating the biochemical, histopathological, and immunohistochemical findings. We concluded that LXA4 mitigated the IND‐induced gastric ulcer via improving the mitochondrial dynamic imbalance and mitochondrial dysfunction, in addition to its anti‐apoptotic, anti‐inflammatory, and antioxidant properties.
AKAP1 mediates high glucose‐induced mitochondrial fission through the phosphorylation of Drp1 in podocytes
Authors: Chen Zhaowei , Ma Yiqiong , Yang Qian , Hu Jijia , Feng Jun , Liang Wei , Ding Guohua 
Published: February 2020

AbstractIncreasing evidence suggests that mitochondrial dysfunction plays a critical role in the development of diabetic kidney disease (DKD), however, its specific pathomechanism remains unclear. A‐kinase anchoring protein (AKAP) 1 is a scaffold protein in the AKAP family that is involved in mitochondrial fission and fusion. Here, we show that rats with streptozotocin (STZ)‐induced diabetes developed podocyte damage accompanied by AKAP1 overexpression and that AKAP1 closely interacted with the mitochondrial fission enzyme dynamin‐related protein 1 (Drp1). At the molecular level, high glucose (HG) promoted podocyte injury and Drp1 phosphorylation at Ser637 as proven by decreased mitochondrial membrane potential, elevated reactive oxygen species generation, reduced adenosine triphosphate synthesis, and increased podocyte apoptosis. Furthermore, the AKAP1 knockdown protected HG‐induced podocyte injury and suppressed HG‐induced Drp1 phosphorylation at Ser637. AKAP1 overexpression aggravated HG‐induced mitochondrial fragmentation and podocyte apoptosis. The coimmunoprecipitation assay showed that HG‐induced Drp1 interacted with AKAP1, revealing that AKAP1 could recruit Drp1 from the cytoplasm under HG stimulation. Subsequently, we detected the effect of drp1 phosphorylation on Ser637 by transferring several different Drp1 mutants. We demonstrated that activated AKAP1 promoted Drp1 phosphorylation at Ser637, which promoted the transposition of Drp1 to the surface of the mitochondria and accounts for mitochondrial dysfunction events. These findings indicate that AKAP1 is the main pathogenic factor in the development and progression of HG‐induced podocyte injury through the destruction of mitochondrial dynamic homeostasis by regulating Drp1 phosphorylation in human podocytes.
Discovery of a new fungicide by screening triazole sulfonylhydrazone derivatives and its downy mildew inhibition in cucumber
Authors: Li Yitao , Lin Jian , Yao Wenqiang , Gao Guoliang , Jing Dewang , Wu Yang 
Published: February 2020

AbstractDowny mildew is a very important detrimental disease that lead reduced to fruits and vegetables. Due to the continuous growth of drug resistance, finding novel fungicides with dissimilar modes of function from present fungicides for controlling downy mildew are imminent. This work is an extension of our preceding research on the original triazole sulfonamide derivatives lead compound. Triazole sulfonamide as a remarkable nitrogen‐containing heterocyclic compound opposed cucumber downy mildew (CDM) develops a quite vital part in the sphere of the study of new farm chemicals. The existing report designs a certain amount of 1,2,4‐triazole‐1,3‐disulfonamide derivatives. Hydrazones have obtained extensive attention in the field of pharmaceutical due to its unique chemical structure and remarkable activity (insecticidal, antibacterial, antifungal and herbicidal). By means of coupling numerous hydrazone with triazole sulfonyl chloride groups, 24 novel derivatives were synthesized. Spectrum analysis of LC‐MS, 1H NMR and 13C NMR were used for characterizing these new compounds. Compared with commercial Cyazofamid using bioassays, most of these compounds displayed preferable fungicidal activities. Moreover, compounds 8q illustrated the greatest CDM resistance (EC50 = 7.776 mg/L). Field efficacy trials revealed that compound 8q fungicidal activity was higher than the purchased agrochemical Cyazofamid and Amisulbrom. Thus, the research declared that 8q displayed a great potential for the application of fungicide against CDM.
Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on‐going viral transcription
Authors: Pannus Pieter , Rutsaert Sofie , De Wit Stéphane , Allard Sabine D , Vanham Guido , Cole Basiel , Nescoi Coca , Aerts Joeri , De Spiegelaere Ward , Tsoumanis Achilleas , Couttenye Marie‐Madeleine , Herssens Natacha , De Scheerder Marie‐Angélique , Vandekerckhove Linos , Florence Eric 
Published: February 2020

AbstractIntroductionViral remission after analytical treatment interruption (ATI), termed post‐treatment control, has been described in a small proportion of HIV‐positive patients. This phenomenon has been separately associated to both low levels of HIV‐1 proviral DNA as well as cell‐associated RNA. We investigated whether the combination of both parameters could help predict delayed viral rebound after treatment interruption (TI).MethodsWe conducted an open single‐arm ATI study in four Belgian HIV reference centres from January 2016 to July 2018. Eligible participants were adults who had fewer than 50 HIV‐1 RNA copies/mL for more than two years, more than 500 CD4 cells/µL for more than three months, and were in general good health. Consenting participants who had fewer than 66 copies total HIV‐1 DNA (t‐DNA) and fewer than 10 copies cell‐associated HIV‐1 unspliced RNA (US‐RNA) per million peripheral blood mononuclear cells (PBMCs), interrupted therapy and were monitored closely. Antiretroviral therapy (ART) was resumed after two consecutive viral loads exceeding 1000 copies or one exceeding 10,000 copies/mL. The primary outcome was the proportion of participants with fewer than 50 HIV‐1 RNA copies/mL 48 weeks after TI. Secondary outcomes were time to viral rebound, the frequency of serious adverse events (AEs) and evolution of t‐DNA and US‐RNA after TI.ResultsAll 16 consenting participants who interrupted therapy experienced rapid viral rebound two to eight weeks after TI. No serious AEs were observed. Levels of t‐DNA and US‐RNA increased after TI but returned to pre‐ATI levels after treatment restart. None of the studied demographic, clinical and biological parameters were predictive of time of viral rebound.ConclusionsThe combination of low levels of t‐DNA and US‐RNA in PBMCs, corresponding respectively to a small and transcriptionally silent viral reservoir, is not predictive of viral remission after TI in patients on ART.
The factors relevant to partial remission in children with type 1 diabetes mellitus after measles vaccination: A retrospective study
Authors: Bektaş Gonca , Önal Hasan , Adal Erdal 
Published: February 2020

AbstractWe aimed to identify the determinants of partial remission in patients with type 1 diabetes mellitus (DM), and whether there is an influence of vaccination against measles on partial remission. This was a retrospective study consisting of consecutive patients diagnosed with type 1 DM followed‐up from 1 September 2010, through 30 November 2011. The study included children vaccinated within 3 months after diagnosis, and children unvaccinated during the first 12 months of the disease. The daily insulin dose, hemoglobin A1c, and C‐peptide levels, and whether children are in partial remission based on the insulin dose‐adjusted HbA1c were recorded at diagnosis and 3, 6, 9, 12, 24, and 36 months. A total of 55 children with type 1 DM were analyzed. Thirty‐one patients (56.4%) reached partial remission during the follow‐up period, whereas 24 of them did not. Patients with diabetic ketoacidosis (DKA) at diagnosis were less likely to reach partial remission than patients without DKA (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.062‐0.946; P = .038). Patients vaccinated against measles were more likely to be in partial remission than patients unvaccinated (OR, 4.2; 95% CI, 1.35‐13; P = .011). Partial remission was significantly associated with the C‐peptide level and insulin dosage at diagnosis P = .002; P = .013, respectively). The lack of DKA, higher C‐peptide level, and lower insulin dosage at diagnosis, and vaccination against measles after diagnosis may have an influence on partial clinical remission in patients with new‐onset type 1 DM.
Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach
Authors: Bhattacharya Manojit , Sharma Ashish R. , Patra Prasanta , Ghosh Pratik , Sharma Garima , Patra Bidhan C. , Lee Sang‐Soo , Chakraborty Chiranjib 
Published: February 2020

AbstractRecently, a novel coronavirus (SARS‐COV‐2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS‐CoV and MERS‐CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS‐COV‐2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex‐(MHC) I and 3 MHC‐II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll‐like receptor‐5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.
The placenta‐brain‐axis
Authors: Rosenfeld Cheryl S. 
Published: February 2020

AbstractAll mammalian species depend on the placenta, a transient organ, for exchange of gases, nutrients, and waste between the mother and conceptus. Besides serving as a conduit for such exchanges, the placenta produces hormones and other factors that influence maternal physiology and fetal development. To meet all of these adaptations, the placenta has evolved to become the most structurally diverse organ within all mammalian taxa. However, commonalities exist as to how placental responses promote survival againstin uterothreats and can alter the trajectory of fetal development, in particular the brain. Increasing evidence suggests that reactions of the placenta to variousin uterostressors may lead to long‐standing health outcomes, otherwise considered developmental origin of health and disease effects. Besides transferring nutrients and gases, the placenta produces neurotransmitters, including serotonin, dopamine, norepinephrine/epinephrine, that may circulate and influence brain development. Neurobehavioral disorders, such as autism spectrum disorders, likely trace their origins back to placental disturbances. This intimate relationship between the placenta and brain has led to coinage of the term, the placenta‐brain‐axis. This axis will be the focus herein, including how conceptus sex might influence it, and technologies employed to parse out the effects of placental‐specific transcript expression changes on later neurobehavioral disorders. Ultimately, the placenta might provide a historical record ofin uterothreats the fetus confronted and a roadmap to understand how placenta responses to such encounters impacts the placental‐brain‐axis. Improved early diagnostic and preventative approaches may thereby be designed to mitigate such placental disruptions.
Climatology of landfalling atmospheric Rivers and associated heavy precipitation over the Indian coastal regions
Authors: Dhana Laskhmi Douluri , Satyanarayana A.N.V. 
Published: February 2020

AbstractThe Indian coastal regions encountered frequently by extreme weather events such as heavy precipitation events (HPE). In the present study, an assessment has been made to understand the climatological relationship between atmospheric rivers (ARs) and HPEs for Indian coastal regions. For this purpose, India Meteorological Department gridded rainfall dataset, and four different reanalyses datasets for the occurrence of ARs were analysed for different seasons during 1980–2015. The influence of ARs towards the cause of HPEs was stronger over the West coast (WC) compared to the East coast of India (ECI). Over the WC the association between HPE with ARs is ~40% (for rainfall events >124.4·mm·day−1) than East coast (EC) by ~28%. The 64.4–124.4·mm·day−1 events are higher over the WC by ~18% compared to ~5% over the EC. While for the events (<64.4·mm·day−1), the percentage of occurrence is moreover the WC (~7%) compared to the EC (~2%). The study reveals that ARs is in good correlation with the occurrence of HPE. Using Poisson regression model, investigated the relationship between the AR totals in the summer and Northeast monsoon and the large‐scale climate indices. A sufficiently significant negative (positive) dependency observed between ARs and the Southern Oscillation Index (SOI) (Indian Ocean Dipole [IOD] and Niño 3.4 indices) with a larger rate of AR occurrence associated with lower SOI values and larger frequency of AR occurrence associated with larger IOD and Niño 3.4 values for both the coasts of India.
Comparisons between marine productivity and terrestrial input records in the Gulf of California over the last 28 ka
Authors: Arellano‐Torres Elsa , Mora‐Rivera Astrid J. , Vázquez‐Romero Paola , Nava‐Sánchez Enrique H. , Kasper‐Zubillaga Juan José , Lozano‐García M. Socorro 
Published: February 2020

ABSTRACTWe study the marine and terrestrial contributions in the Gulf of California (GC) to understand the relationship between continental climate and oceanographic variability over the last 28 ka. In Core AII125‐8‐JPC‐20, we examine aeolian and riverine inputs as nutrients for biological productivity. We use biogenic silica (%opal), total organic carbon (%TOC) and calcium carbonate (%CaCO3) as proxies for primary productivity, and lithic fraction distributions as proxies for terrigenous transport. At the core site, biogenic and lithic components are in phase at millennial‐scale in response to regional climate conditions. During the Late Pleistocene, the GC shelf area was above sea level and the western margin showed transient episodes of increased fluvial inputs. Episodic increases in %opal and reduced %TOC suggest upwelling events but ineffective C‐export to the sediment. During stadial events (Heinrich 2, Heinrich 1, Younger Dryas), regional declines in %opal, but increases in %CaCO3 and TOC, suggest efficient C‐export by carbonate organisms. During most of the Holocene, dust inputs are higher. Episodic increases in %TOC suggest higher C‐accumulation, although this is not controlled by siliceous or calcareous organisms. In the GC, besides upwelling and current advection, nutrient inputs driven by terrestrial climate have an impact on the biological C‐pump. © 2020 John Wiley & Sons, Ltd.
Wavelet transforms in separation science for denoising and peak overlap detection
Authors: Wahab Muhammad Farooq , O'Haver Thomas C. 
Published: February 2020

AbstractWavelet transform is a versatile time‐frequency analysis technique, which allows localization of useful signals in time or space and separates them from noise. The detector output from any analytical instrument is mathematically equivalent to a digital image. Signals obtained in chemical separations that vary in time (e.g., high‐performance liquid chromatography) or space (e.g., planar chromatography) are amenable to wavelet analysis. This article gives an overview of wavelet analysis, and graphically explains all the relevant concepts. Continuous wavelet transform and discrete wavelet transform concepts are pictorially explained along with their chromatographic applications. An example is shown for qualitative peak overlap detection in a noisy chromatogram using continuous wavelet transform. The concept of signal decomposition, denoising, and then signal reconstruction is graphically discussed for discrete wavelet transform. All the digital filters in chromatographic instruments used today potentially broaden and distort narrow peaks. Finally, a low signal‐to‐noise ratio chromatogram is denoised using the procedure. Significant gains (>tenfold) in signal‐to‐noise ratio are shown with wavelet analysis. Peaks that were not initially visible were recovered with good accuracy. Since discrete wavelet transform denoising analysis applies to any detector used in separation science, researchers should strongly consider using wavelets for their research.
Success of Hypoglossal Nerve Stimulation Using Mandibular Advancement During Sleep Endoscopy
Authors: Mulholland Graeme B. , Dedhia Raj C. 
Published: February 2020

Objectives/HypothesisHypoglossal nerve stimulation (HGNS) effectively treats obstructive sleep apnea in select patients. Drug‐induced sleep endoscopy (DISE) is required for HGNS candidacy. Data suggest that mandibular advancement (MA) devices and HGNS share similar target populations. We aimed to test the association between MA's effect on the velum and lateral walls during DISE in relation to the improvement in the apnea‐hypopnea index (AHI) with HGNS.Study DesignProspective case seriesMethodsAll patients completed preoperative polysomnography or home sleep study, DISE with MA prior to HGNS implantation, and full‐night efficacy sleep tests. Adult patients with body mass index (BMI) ≤ 35 and AHI ≥ 15 were included. Two independent reviewers scored DISE videos.ResultsForty‐six patients were included from October 2015 to January 2019. Mean BMI (standard deviation) was 28.5 (3.7) kg/m2. Patients with a reduced airway response to MA had greater AHI improvement than patients with a robust response (21.7, 95% confidence interval [CI]: 14.4 to 29.0 vs. 4.9, 95% CI: −8.9 to 18.6; P = .03). Patients with complete baseline collapse at the velum and lateral walls (n = 11) had less response compared to those with partial collapse (n = 35) (AHI reduction of 4.4 [95% CI: −8.6 to 17.4] vs. 22.3 [95% CI: 15.1 to 29.6; P = .02]).ConclusionsPatients having significant airway improvement in the upper pharynx with MA during DISE appear less likely to succeed with HGNS. This phenomenon might be secondary to the worsened baseline obstruction of the upper pharynx in such patients.Level of Evidence4 Laryngoscope, 2020