bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage induced neuroinflammation in neurodegenerative disease
Authors: Song Xuan , AW Theeng Mei , Ma Fulin , Leung Danny , Herrup Karl 
Published: December 2020

AbstractBackgroundThe neurological symptom is highly related to the activation of innate immune system in the brain in neurodegenerative disease. The robust activation of microglia, which includes an overproduction of cytokines, creates a pro‐inflammatory environment that greatly contributes to the neuronal cell damage.MethodDNA damage was induced by either direct triggers of double strands break or blocking DNA damage repair. Conditioned media from microglia culture was collected and treated to the neuronal culture. Different neuronal parameters, including the morphological changes, synaptic counts and death markers, were measured afterwards.ResultIn microglia, DNA damage induces elevated level of cytoplasmic DNA, which primes the anti‐virus innate immune response via the cytosolic DNA sensor, STING. Knockdown of STING or inhibition of STING activity rescued the inflammatory response, specifically, the overproduction of cytokines. Cytosolic DNA species also works through the AIM2‐containing inflammasome to process pro‐IL‐1β to its active form, IL‐1β. DNA damage in microglia leads to the secretion of pro‐inflammatory cytokines to the conditioned with sever neuronal cell damage.ConclusionThe present work pointed out the fundamentality of accumulated DNA damage in triggering the activation of pro‐inflammatory pathway in the immune cells. Upon DNA damage, brain microglia, the major immune cells of the central nervous system become activated and assume a neurotoxic pro‐inflammatory phenotype. This also calls attention to the importance of the microglia‐neuron interaction in brain diseases. Meanwhile, the evidence for the presence of cytoplasmic DNA in other cell types under different disease conditions are also relevant to our understanding of a wider range of neurodegenerative diseases.
Loneliness and social engagement in older adults based in Lombardy during COVID‐19 lockdown: The long‐term effects of social networking sites training course
Authors: Rolandi Elena , Vaccaro Roberta , Abbondanza Simona , Casanova Georgia , Pettinato Laura , Colombo Mauro , Guaita Antonio 
Published: December 2020

AbstractBackgroundOlder people are at greater risk of infection and mortality from COVID‐19 and 52.3% of the deceased in Italy are Lombardy’s residents. Moreover, lockdown measurements may disproportionately affect elderly, since they are less familiar with communication technology used to overcome the lack of in person social contacts. The present study aimed at exploring how older adults residing in Lombardy are experiencing the lockdown period, in relation to loneliness, social isolation and use of communication technology.MethodIn the first two weeks of May (2020) a telephone interview was conducted with people aged between 81 and 85, residing in the community, who participated in a study aimed at evaluating the impact of Social Networking Sites (SNS) use and older people’s social relationship (clinicaltrials.gov: NCT04242628). We collected information on SNS use, self‐perceived loneliness (UCLA scale 3‐item), social engagement with family and friends (Lubben Social Network Scale 6‐item). Among the eligible individuals (N=144), 1 deceased, 4 refused and 9 were unreachable, resulting in a sample of 130 interviewed. For the aim of the present investigation, participants were stratified as trained (N=60) and untrained (N=70) for SNS use, based on their attendance to group courses held last year as part of the main experimental study.ResultTrained and untrained participants were comparable for age, sex, education, percentage of living alone, global cognition, depressive symptoms and comorbidity (Table 1). Participants trained for SNS use reported significantly higher usage of Facebook and WhatsApp and reduced feeling of being left out during the COVID‐19 lockdown (Table 2). Moreover, a trend toward significance was found for an inverse relationship between WhatsApp usage frequency and feeling of lack of companionship (rs = ‐0.257, p = 0.051; Table 3).ConclusionThough SNS are unable to completely replace in person contact, these preliminary results support the utility to train older adults for SNS use in order to improve their social inclusion, even in extreme conditions of self‐isolation and vulnerability due to COVID‐19 pandemic.
Lysosome‐autophagosome defects mediate proteinopathy in early stages of Alzheimer’s disease
Authors: Mustaly Sarah H , Beaman Kenneth D , Gilman‐Sachs Alice , Schrank Sean , Marr Robert , Stutzmann Grace E 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by abnormal protein aggregation and synaptic deficits. To regulate normal cellular recycling of cellular debris, lysosomes require an acidic environment which is maintained by an active vacuolar H+‐ATPase (V‐ATPase proton pump). The acidic pH in lysosomes is essential for autophagy, a catabolic pathway to degrade cellular proteins. In AD, V‐ATPase disruption can lead to abnormal β‐amyloid and tau accumulation. A candidate mechanism concurrent with V‐ATPase defects is Ca2+ dyshomeostasis, which alters the ion exchange and thus pH within these organelles. We hypothesize that altered Ca2+ signaling disrupts V‐ATPase ion exchange and instigates AD pathology.MethodImmunohistochemistry in fixed brain slices was used to determine expression of V‐ATPase subunits (V1B2, V0a1), lysosomes (Lamp1), hyperphosphorylated tau (S262) and mature autophagosomes (LC3B) in 4‐month old 3xTg‐AD mice and non‐transgenic (NTg) controls with or without a 30‐day Ryanodex treatment (NAM of RyR; 10mg/kg). Lysosomal pH upon RyR stimulation with caffeine (20mM) was measured in RyR‐overexpressing HEK cells and iN using Lysosensor. Induced human neurons (iN) transformed from AD patient fibroblasts were used to measure, autophagosomes, β‐amyloid, and hyperphosphorylated tau levels after500nM bafilomycin V‐ATPase inhibitor treatment.ResultV‐ATPase and lysosome markers are diminished in brains of 3xTg‐AD mice relative to NTg, whereas LC3B expression is increased. These phenotypes were restored to NTg levels after Ryanodex treatment in 3xTg‐AD mice. Additionally, increased aberrant RyR‐Ca2+ signaling alkalizes lysosomes and increases expression of hyperphosphorylated tau and autophagosomes in iN and RyR‐overexpressing HEK cells, with no significant difference with of β‐amyloid levels.ConclusionPrior to overt histopathology or cognitive deficits, decreased V‐ATPase expression on acidic compartments and increased autophagosomes in 3xTg‐AD mice reflects impaired lysosomal activity, which is mediated through upstream RyR‐Ca2+ dyshomeostatis. Increased RyR‐mediated Ca2+ release alkalizes lysosomes pH resulting in abnormal intracellular protein aggregates, demonstrating that aberrant intracellular Ca2+ signaling in early AD disrupts autophagy and protein clearance.
Formic Acid‐Assisted Selective Hydrogenolysis of 5‐Hydroxymethylfurfural to 2,5‐Dimethylfuran over Bifunctional Pd Nanoparticles Supported on N‐Doped Mesoporous Carbon
Authors: Hu Bin , Warczinski Lisa , Li Xiaoyu , Lu Mohong , Bitzer Johannes , Heidelmann Markus , Eckhard Till , Fu Qi , Schulwitz Jonas , Merko Mariia , Li Mingshi , Kleist Wolfgang , Hättig Christof , Muhler Martin , Peng Baoxiang 
Published: December 2020

AbstractBiomass‐derived 5‐hydroxymethylfurfural (HMF) is regarded as one of the most promising platform chemicals to produce 2,5‐dimethylfuran (DMF) as a potential liquid transportation fuel. Pd nanoparticles supported on N‐containing and N‐free mesoporous carbon materials were prepared, characterized, and applied in the hydrogenolysis of HMF to DMF under mild reaction conditions. Quantitative conversion of HMF to DMF was achieved in the presence of formic acid (FA) and H2 over Pd/NMC within 2 h. The reaction mechanism, especially the multiple roles of FA, was explored through a detailed comparative study by varying hydrogen source, additive, and substrate as well as by applying in situ ATR‐IR spectroscopy. The major role of FA is to shift the dominant reaction pathway from the hydrogenation of the aldehyde group to the hydrogenolysis of the hydroxymethyl group via the protonation by FA at the C‐OH group, lowering the activation barrier of the C−O bond cleavage and thus significantly enhancing the reaction rate. XPS results and DFT calculations revealed that Pd2+ species interacting with pyridine‐like N atoms significantly enhance the selective hydrogenolysis of the C−OH bond in the presence of FA due to their high ability for the activation of FA and the stabilization of H−.
Morphology, mechanical, and physical properties of wet‐spun cellulose acetate fiber in different solvent‐coagulant systems and in‐situ crosslinked environment
Authors: Swapnil Soham Irtiza , Datta Nondita , Mahmud Md Musavvir , Jahan Rumana A. , Arafat M. Tarik 
Published: December 2020

AbstractWet spinning is a popular fiber manufacturing process where the effects of solvent and coagulant on the wet‐spun fiber are significant. In this study, we have explored the effect of solvent‐coagulant interaction and in‐situ crosslinking on the wet‐spun cellulose acetate (CA) fiber. Investigation on 12 different solvent‐coagulant systems revealed that variation in the systems resulted in significant variance in morphology and mechanical property of the fiber. Remarkable increase in mechanical property was observed after in‐situ crosslinking with citric acid and polyethylene glycol (PEG). Inclusion of sodium hypophosphite (NaH2PO2) as catalyst further increased tensile modulus (~407%) and crystallinity index (~46%) compared to CA fiber crosslinked with only citric acid. It was established that fiber from CA‐DMSO solution crosslinked with 10% citric acid and 10% PEG extruded in ethanol showed the highest tensile modulus (~30 MPa). This in‐depth study found an appropriate combination of solvent‐coagulant for forming stable CA fiber, with the addition of crosslinkers and catalyst further increasing the strength and usability of the fiber.
Sex Differences in Gender‐Diverse Expressions and Identities among Youth with Autism Spectrum Disorder
Authors: Brunissen Ludivine , Rapoport Eli , Chawarska Katarzyna , Adesman Andrew 
Published: December 2020

A growing body of evidence supports a potential link between autism spectrum disorder (ASD) and gender dysphoria, yet few studies have looked at sex differences in the co‐occurrence of gender diversity and ASD. The aim of this study was to characterize sex differences in gender‐diverse expressions and identities, as well as gender‐related concerns, in youth with ASD. Parents of youth with ASD ages 6–21 (n = 163) completed an online questionnaire about their child's gender expression and identity. Sex‐typed behaviors during childhood were measured using the Gender Identity Questionnaire (GIQ). Semi‐partial Kendall correlations and chi‐square tests were used to compare gender non‐conformity, gender‐diverse identities, and gender‐related concerns between sexes. Sex‐based differences in mean GIQ score and individual GIQ items were evaluated using a linear regression and semi‐partial Kendall correlations, respectively. All regressions and correlations controlled for child age. Parents of girls were more likely to report child appearances and mannerisms that were less concordant with their child's birth sex. Based on parent‐report, girls had lower mean GIQ scores, indicating greater cross‐gendered/fewer same‐gendered behaviors in childhood. Lastly, parents of girls with ASD were more likely to report that their daughters experienced anxiety due to gender‐related concerns and discomfort during puberty than parents of boys. These findings suggest that girls with ASD seem more likely have gender‐diverse preferences, mannerisms, and appearances that fall outside of traditional gender norms. Gender‐related concerns appear to be a source of real distress in girls with ASD, highlighting the need for individualized support, especially during puberty.Lay SummaryDespite evidence of a potential link between autism and gender diversity, few studies have explored differences in gender identity/expression between boys and girls with autism. Based on parent responses, we found that girls with autism are more likely than boys to have appearances and mannerisms, as well as behaviors during childhood, that fall outside of the traditional gender role. The unique profile of girls with autism and their elevated distress over gender‐related concerns call for individualized support during adolescence.
Attend Less, Fear More: Elevated Distress to Social Threat in Toddlers With Autism Spectrum Disorder
Authors: Macari Suzanne L. , Vernetti Angelina , Chawarska Katarzyna 
Published: December 2020

Differential emotional reactivity to social and nonsocial stimuli has been hypothesized but rarely examined empirically in ASD despite its potential importance for development of social motivation, cognition, and comorbid psychopathology. This study examined emotional reactivity, regulation, and attention to social and nonsocial threat in toddlers with ASD (n = 42, Mage: 22 months) and typically developing (TD) toddlers (n = 22, Mage: 23 months), and their mutual associations with autism symptom severity. Participants were exposed to social (stranger), nonsocial (mechanical objects), and ambiguous (masks) threats, and their intensity of distress (iDistress), attention to threat (Attention), and presence of emotion regulation (ER) strategies were measured. Autism symptom severity was quantified using the Autism Diagnostic Observation Schedule‐2. In response to social threat, toddlers with ASD exhibited elevated iDistress (P < 0.038) but lower Attention (P < 0.002) and a wider variety of ER strategies (P < 0.040) compared to TD controls, though their ER strategies were less likely to be social. However, nonsocial and ambiguous threat elicited lower iDistress in ASD than in TD toddlers (P = 0.012 and P = 0.034, respectively), but comparable Attention and ER strategy use. Autism severity was not associated with iDistress. The study demonstrates elevated emotional salience but diminished attentional salience of social threat in ASD. A failure to attend adequately to social threats may restrict opportunities to appraise their threat value and engender often observed in ASD negative emotional responses to novel social situations. Early atypical emotional reactivity may independently contribute to the shaping of complex autism phenotypes and may be linked with later emerging affective and behavioral symptoms.Lay SummaryCompared to typically developing toddlers, toddlers with ASD show diminished attention yet enhanced distress in response to social threat. Poor attention to potential social threat may limit opportunities to assess its threat value and thus contribute to often observed negative emotional responses to novel social situations. Identifying the precursors of atypical emotional reactivity in infancy and its links with later psychopathology will inform about novel treatment targets and mechanisms of change in the early stages of ASD. Autism Res 2021, 14: 1025–1036. © 2020 International Society for Autism Research, Wiley Periodicals, LLC
The Anti‐G0 Manifesto: Should a problematic construct (G0) with no biological reality be removed from the cell cycle? Yes!
Authors: Cooper Stephen 
Published: December 2020

AbstractIt is widely accepted that there exists a “resting” or “quiescent” state where a growing cell leaves the cell cycle to enter what is often called the “G0‐phase.” I propose that there is no biological reality to the “G0‐phase.” The experimental basis for proposing a G0‐phase is re‐examined and re‐analyzed here showing that the G0‐phase is an anthropomorphic construct with no biological reality.
A rapid and sensitive ultra‐high‐pressure liquid chromatography–tandem mass spectrometry method for the determination of notoginsenoside Ft1 in rat plasma with application to pharmacokinetic study
Authors: Ju Zhengcai , He Chunyong , Li Jia , Yang Li , Wang Zhengtao 
Published: December 2020

AbstractNotoginsenoside Ft1 (NGFt1), a dammarane triterpene glycoside isolated from Panax notoginseng, showed potent effective in stimulating platelet aggregation in our previous assay, yet its pharmacokinetic behavior is still unclear. This study describes a rapid and sensitive ultra‐high‐pressure LC–tandem mass spectrometry assay for determining of NGFt1 in rat plasma. Methanol‐mediated precipitation was used for sample pre‐treatment. Chromatographic separation was achieved on a C18 column with gradient elution using water and acetonitrile as mobile phase. Determination was obtained using an electrospray ionization source in negative selected reaction monitoring (SRM) mode at the transitions of m/z 915.9 → m/z 783.8 and m/z 799.8 → m/z 637.8 for NGFt1 and internal standard, respectively. The assay was linear over the concentration range 0.25–2500 ng/mL (r > 0.995) with the lower limit of quantification of 0.25 ng/mL. The intra‐ and inter‐day precisions (relative standard deviation, %) ranged 1.65%–9.84% and 2.46%–13.49%, respectively, whereas accuracy (relative recovery, %) ranged from 96.21% to 99.45%, respectively. The recovery ranged from 95.09% to 102.22% and the matrix effect from 98.29% to 100.13%. The analyte was stable under tested storage conditions. The method has been successfully applied to a preclinical pharmacokinetic study in rats after a single intravenous (2 mg/kg) and oral (50 mg/kg) administration.
Validated HPLC‐MS/MS method for quantitation of AMG 510, a KRAS G12C inhibitor, in mouse plasma and its application to a pharmacokinetic study in mice
Authors: Madhyastha Naveena , Samantha Swapan Kumar , Dittakavi Sreekanth , Markose Meenu , Mallurwar Sadanand Rangnathrao , Zainuddin Mohd , Mullangi Ramesh 
Published: December 2020

AbstractAMG 510 is the first‐in‐class KRASG12C inhibitor, currently in phase 2 clinical trials as an orphan drug to treat non‐small cell lung cancer patients. We developed and validated a sensitive, selective, and high‐throughput HPLC‐MS/MS method for the quantitation of AMG 510 in mouse plasma per the regulatory guideline of the US Food and Drug and Administration. AMG 510 and the IS (MRTX‐1257) were extracted from mouse plasma using tert‐butyl methyl ether and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 25:75, v/v) at a flow rate of 0.65 mL/min on an Atlantis dC18 column. AMG 510 and the IS eluted at ~0.95 and 0.73 min, respectively. AMG 510 and the IS were detected by positive electrospray ionization in multiple reaction monitoring using transition pair (Q1 → Q3) m/z 561.1 → 134.1 and m/z 566.5 → 98.2, respectively. Excellent linearity was achieved in the concentration range of 1.08–5040 ng/mL (r > 0.0996). No matrix effect and carryover were observed. Intra‐ and inter‐day accuracies and precisions were within the acceptance range. AMG 510 was demonstrated to be stable under the tested storage conditions. This novel method has been applied to a pharmacokinetic study in mice.
Global metabolic profiling of hemorrhagic shock and resuscitation
Authors: Xu Ping , Xu Wei , Gao Songyan , Che Yanting , Zhao Ping , Lu Shengfang , Wang Yong , Chen Xiaoqing , Zhang Qun , Chen Junjie , Zheng Xingfeng , Huang Gang , He Guibing , Liu Xinru 
Published: December 2020

AbstractHemorrhagic shock (HS) is a medical emergency during trauma. Significant loss of tissue perfusion may result in cellular hypoxia, organ damage and death. The primary treatment of HS is control of the source of bleeding as soon as possible and fluid replacement (crystalloid solutions and blood transfusion). Metabolomics can identify novel biomarkers for various functional and organic diseases. Therefore, systematic exploration of the biological mechanisms of HS and blood transfusion enables the optimization of treatments for HS to reduce the occurrence of organ damage. In this study, a global metabolic profiling strategy is applied to evaluate metabolic changes in the HS rat model. A serum metabolic network with 58 significant metabolites was constructed for HS and resuscitation. Our investigation will offer insights into the pathogenesis.
Evaluation of alkylamines and stationary phases to improve LC–MS of oligonucleotides
Authors: Bartlett Michael G. , Omuro Shogo 
Published: December 2020

AbstractThis study evaluated four bridged‐ethylene hybrid (BEH) columns containing C18 (130 Å), peptide C18 (300 Å), phenyl, or a mixed‐mode charged surface hybrid (CSH C18) using a wide range of antisense oligonucleotide therapeutics. The BEH C18, peptide, and phenyl columns were all capable of providing significant retention of oligonucleotide samples across multiple ion‐pairing systems using alkylamines and 1,1,1,3,3,3,‐hexafluoroisopropanol (HFIP). The retention of the oligonucleotides varied depending on the choice of alkylamine, with the order of retention being dimethylcyclohexylamine > diisopropylethylamine > triethylamine. The selectivity of these columns for several closely eluting impurities was similar. Although overall the C18, peptide, and phenyl columns were all found to be capable of analyzing oligonucleotide therapeutics, the phenyl column was found to be the most retentive and the C18 column provided the best peak shape. The CSH C18 column was found to be degraded by the alkylamine‐HFIP mobile phase despite the mobile phase being within the pH stability range of the column.
Mechanical properties of low‐diameter balloon expandable covered stents
Authors: Blais Benjamin , Carr Karen , Sinha Sanjay P , Salem Morris M , Levi Daniel S 
Published: December 2020

AbstractObjectivesTo determine over‐dilation potential of commercially available covered stents.BackgroundCovered stents including the Atrium iCast, Gore VBX, and Lifestream stents (LS) can treat ruptures, dissections, and aneurysms in small vessels. Especially in growing patients, stents often require serial dilations beyond their implant or nominal diameters. Tolerance of serial dilations is clinically important information for interventionalists.MethodsSerial dilations of 5–12 mm iCast, VBX, and LS covered stents were performed in 1–2 mm increments (up to 20 mm). With each dilation, foreshortening and recoil were measured, and stent strut and covering integrity were assessed. High‐pressure balloons were used to expand the stents until they fractured or could not be further expanded.ResultsThe 5–8 mm LS tolerated dilation to 14.5–16 mm. The 10–12 mm LS stents tolerated dilation to 18 mm and fractured on the 20 mm balloon. LS stents foreshortened 35%–45% on average after 8 mm of over‐dilation and had 5%–10% recoil on <6 mm over‐dilation. All iCast stents tolerated dilation to 12–13 mm and required fracture for dilation to >14 mm. ICast stents foreshortened 19%–29% at maximum dilation, with 3–6% recoil on <2 mm over‐dilation, and < 3% thereafter. VBX stents over‐dilated to 2.9–4.7 mm above nominal, foreshortening 40%–50% after 4–6 mm of over‐dilation before collapsing into a ring. VBX stent recoil was <2.5% on all dilations.ConclusionsLS stents had the greatest over‐dilation potential. VBX stents had the least recoil but tended to foreshorten significantly 3–4 mm above nominal. Regardless of nominal size, all iCast stents (including the 5 mm) tolerated dilation to a maximum of 12–13 mm.
Early diagnosis and antibiotic treatment for fulminant Clostridium difficile infection
Authors: Fukushima Kazutaka , Inokuchi Ryota , Hirayama Ichiro , Hiruma Takahiro , Doi Kent 
Published: December 2020

AbstractIn fulminant Clostridium difficile infection (CDI), early diagnosis is important, and early diagnosis could save fulminant CDI patients that do not qualify for surgery due to severe complicating conditions by conservative antibiotic therapy.