bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sterile inflammation drives multiple programmed cell death pathways in the gut
Authors: Ruera Carolina N , Miculán Emanuel , Pérez Federico , Ducca Gerónimo , Carasi Paula , Chirdo Fernando G 
Published: September 2020

Abstract
Intestinal epithelial cells have a rapid turnover, being rapidly renewed by newly differentiated enterocytes, balanced by massive and constant removal of damaged cells by programmed cell death (PCD). The main forms of PCD are apoptosis, pyroptosis, and necroptosis, with apoptosis being a noninflammatory process, whereas the others drive innate immune responses. Although apoptosis is thought to be the principal means of cell death in the healthy intestine, which mechanisms are responsible for PCD during inflammation are not fully understood. To address this question, we used an in vivo model of enteropathy in wild-type mice induced by a single intragastric administration of the p31-43 gliadin peptide, which is known to elicit transient MyD88, NLRP3, and caspase-1-dependent mucosal damage and inflammation in the small intestine. Here, we found increased numbers of TUNEL+ cells in the mucosa as early as 2 h after p31-43 administration. Western blot and immunofluorescence analysis showed the presence of caspase-3-mediated apoptosis in the epithelium and lamina propria. In addition, the presence of mature forms of caspase-1, IL-1β, and gasdermin D showed activation of pyroptosis and inhibition of caspase-1 led to decreased enterocyte death in p31-43-treated mice. There was also up-regulation of RIPK3 in crypt epithelium, suggesting that necroptosis was also occurring. Taken together, these results indicate that the inflammatory response induced by p31-43 can drive multiple PCD pathways in the small intestine.
Efficacy of tocilizumab in COVID‐19: A systematic review and meta‐analysis
Authors: Aziz Muhammad , Haghbin Hossein , Abu Sitta Emad , Nawras Yusuf , Fatima Rawish , Sharma Sachit , Lee‐Smith Wade , Duggan Joan , Kammeyer Joel A. , Hanrahan Jennifer , Assaly Ragheb 
Published: September 2020

AbstractThe efficacy of tocilizumab (TOC), monoclonal antibody against interleukin‐6 (IL‐6) receptor, in patients with coronavirus disease‐2019 (COVID‐19) patients has led to conflicting results. We performed a systematic review and meta‐analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID‐19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian‐Laird/Random‐effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: −0.06; CI: −0.12 to −0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: −0.12; CI: −0.18 to −0.06; p < .01) and need for mechanical ventilation (RD: −0.11; CI: −0.19 to −0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID‐19. Randomized controlled trials are needed to validate this.
Clinical laboratory characteristics in patients with suspected COVID‐19: One single‐institution experience
Authors: Fei Fei , Smith John A. , Cao Liyun 
Published: September 2020

AbstractObjectivesSince December 2019, the outbreak of coronavirus disease 2019 (COVID‐19) has become a worldwide pandemic. The aim of the study is to investigate the demographic, clinical, and laboratory characteristics in suspected COVID‐19 patients in our institution.MethodsIn this retrospective study, we investigated suspected COVID‐19 patients admitted to the University of Alabama at Birmingham with a request for an interleukin‐6 send‐out test, from March 28 to June 27, 2020. Patients' demographic, clinical, and laboratory characteristics were collected by chart review.ResultsFifty patients suspected with COVID‐19 were included in our study, of whom 24 patients were positive with severe acute respiratory syndrome coronavirus‐2 infection and 26 were negative. During the observation period, 30 patients were discharged, 17 died during hospitalization, and three remained in hospital. Compared to non‐COVID‐19 patients, COVID‐19 patients had older age, more comorbidities, and elevated levels of inflammation markers such as erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), serum ferritin, and lactate dehydrogenase (LDH). However, there was no significant difference in laboratory data between survivors and nonsurvivors in COVID‐19 patients in our study.ConclusionThis study indicated that potential risk factors of older age, multiple comorbidities, and high levels of ESR, CRP, serum ferritin, and LDH could help the clinician to identify potential COVID‐19 patients. However, this data needs to be further validated in a larger population.
Micro‐Raman study of crichtonite group minerals enclosed into mantle garnet
Authors: Alifirova Taisia , Rezvukhin Dmitriy , Nikolenko Evgeny , Pokhilenko Lyudmila , Zelenovskiy Pavel , Sharygin Igor , Korsakov Andrey , Shur Vladimir 
Published: September 2020

AbstractWe report the first comprehensive micro‐Raman study of crichtonite group minerals (CGM) as inclusions in pyropic garnet grains from peridotite and pyroxenite mantle xenoliths of the Yakutian kimberlites as well as in garnet xenocrysts from the Aldan shield lamprophyres (Russia). The CGM form (i) morphologically oriented needles, lamellae, and short prisms and (ii) optically unoriented subhedral to euhedral grains, either single or intergrown with other minerals. We considered common mantle‐derived CGM species (like loveringite, lindsleyite, and their analogues), with Ca, Ba, or Sr dominating in the dodecahedral A site and Zr or Fe in the octahedral B site. The Raman bands at the region of 600–830 cm−1are indicative of CGM and their crystal‐chemical distinction, although the intensity and shape of the bands appear to be dependent on laser beam power and wavelength. The factor‐group analysis based on the loveringite crystal structure showed the octahedral and tetrahedral cation groups with 18fand 6cWyckoff positions, namely, dominantlyTiO6and to a lower extentCrO6,MgO4, andFeO4groups, to be the major contributors to the Raman spectral features. The ionic groups with dodecahedral (M0) and octahedral (M1) coordination are inactive for Raman scattering while active in infrared absorption. A number of observed Raman modes in the CGM spectra are several times lower than that predicted by the factor group analysis. The noticed broadening of modes in the CGM Raman spectra may result from a combining of bands at the narrow frequency shift regions. Solid solution behavior, luminescence, and partial metamictization of the CGM may exert additional influence on the Raman band shape. The Raman spectral features showed CGM to be accurately identified and distinguished from other Ti‐, Fe‐, Cr‐, and Zr‐containing oxides (e.g., ilmenite or those of spinel and magnetoplumbite groups) occurring as accessory mantle minerals.
Detection of a multi‐disease biomarker in saliva with graphene field effect transistors
Authors: Kumar Narendra , Gray Mason , Ortiz‐Marquez Juan C. , Weber Andrew , Desmond Cameron R. , Argun Avni , van Opijnen Tim , Burch Kenneth S. 
Published: September 2020

AbstractHuman carbonic anhydrase 1 (CA1) has been suggested as a biomarker for identification of several diseases including cancers, pancreatitis, diabetes and Sjogren's syndrome. However, the lack of a rapid, cheap, accurate and easy‐to‐use quantification technique has prevented widespread utilization of CA1 for practical clinical applications. To this end, we present a label‐free electronic biosensor for detection of CA1 utilizing highly sensitive graphene field effect transistors (G‐FETs) as a transducer and specific RNA aptamers as a probe. The binding of CA1 with aptamers resulted in a positive shift in Dirac voltage VD of the G‐FETs, the magnitude of which depended on target concentration. These aptameric G‐FET biosensors showed the binding affinity (KD) of ~2.3 ng/ml (70 pM), which is four orders lower than that reported using a gel shift assay. This lower value of KD enabled us to achieve a detection range (10 pg/ml –100 ng/ml) which is well in line with the clinically relevant range. These highly sensitive devices allowed us to further prove their clinical relevance by successfully detecting the presence of CA1 in human saliva samples. Utilization of this label‐free biosensor could facilitate the early‐stage identification of various diseases associated with changes in concentration of CAs.
All in the Levels—Programmed Death-Ligand 1 Expression as a Biomarker for Immune Checkpoint Inhibitor Response in Patients with Gastrointestinal Cancer
Authors: Das Satya , Cimino Sarah , Davis Shemeka , Ciombor Kristen 
Published: September 2020

Abstract

Immune checkpoint inhibitors (ICIs) benefit patients with rare subsets of gastrointestinal (GI) cancer. Significant interest exists to identify predictive biomarkers that may increase the applicability of ICI therapy for these patients. Programmed death ligand 1 (PD-L1) is one such candidate; however, this biomarker has well-chronicled limitations. Combined positive score (CPS) ≥1 is the minimum PD-L1 expression threshold necessary for patients with gastric or gastroesophageal junction (GEJ) cancer to qualify for treatment with pembrolizumab; however, studies suggest that patients with higher CPS scores may derive greater benefit. We present the cases of two patients, both with low tumor mutational burden, microsatellite stable, and CPS ≥70 GI tumors (cholangiocarcinoma and GEJ cancer), who have achieved excellent tumor control with pembrolizumab. We postulate that, by testing for CPS in all patients with GI cancer and identifying a CPS threshold predictive of ICI response, PD-L1 expression could identify the patiets with GI cancer, in tissue agnostic fashion, who could benefit from ICI therapy.
Application of choline chloride deep eutectic solvents and high‐speed counter‐current chromatography to the extraction and purification of flavonoids from the thorns of Gleditsia sinensis Lam
Authors: Yu Jinqian , Zhao Lei , Sun Xiaowei , Sun Chenglong , Wang Xiao 
Published: September 2020

AbstractIntroductionFlavonoids are the most important and effective constituents in the thorns of Gleditsia sinensis Lam., which have been known to show antimicrobial, antiviral, anticancer, and anticoagulant activities. However, efficient extraction and separation methods for these flavonoids are not currently established.ObjectiveTo develop an efficient method for efficient extraction and rapid separation of flavonoids from the thorns of G. sinensis using choline chloride deep eutectic solvents (DESs) and high‐speed counter‐current chromatography (HSCCC).MethodologyAs for extraction, DES composed of choline chloride and 1,4‐butanediol at 1:4 mole ratio, at an extraction temperature of 55°C, 20% of water content, 1:30 mg/mL for solid–liquid ratio, and 45 min for extraction time were selected as the optimised extraction method for flavonoids from the thorns of G. sinensis. As for separation, dichloromethane–methanol–n‐butanol–water (4:3:0.5:2, v/v) was applied to develop a successful strategy for purification of the flavonoids by HSCCC.ResultsTotally, five flavonoids, including padmatin (1, 3.7 mg), isovitexin (2, 2.5 mg), 3′,5,5′,7‐tetrahydroxyflavanonol (3, 11.2 mg), 7,4′‐dihydroxy‐5,3′‐dimethoxyflavanonol (4, 4.1 mg), and quercetin (5, 3.8 mg), were successfully obtained from 250 mg of the extracted flavonoids by HSCCC.ConclusionResults demonstrated that the combination of DES and HSCCC is a powerful technique for the extraction, and isolation of flavonoids from the thorns of G. sinensis compared with conventional organic solvent extraction and column chromatography, which have been proven to provide higher extraction efficiency for flavonoids and rapidly obtain the quality control markers of flavonoids from the investigated plant.
Psychiatric and general health effects of COVID‐19 pandemic on children with chronic lung disease and parents' coping styles
Authors: Ademhan Tural Dilber , Emiralioglu Nagehan , Tural Hesapcioglu Selma , Karahan Sevilay , Ozsezen Beste , Sunman Birce , Nayir Buyuksahin Halime , Yalcin Ebru , Dogru Deniz , Ozcelik Ugur , Kiper Nural 
Published: September 2020

AbstractBackgroundWe aim to assess the anxiety and depressive symptoms related to the COVID‐19 pandemic in children with chronic lung disease and their parents and also to evaluate parents' coping strategies.MethodsParents of children aged 4–18 years, with chronic lung disease (study group n = 113) and healthy control (n = 108) were enrolled in the study. General Health Questionnaire‐12, specific COVID‐19 related anxiety questions, The Coping Orientation to Problems Experienced inventory, coronavirus‐related psychiatric symptom scale in children–parental form were used to analyze the psychiatric effects of COVID‐19. Parents were also asked about how online education affected their family life and children. All data were compared between children/parents in the study and control groups. Risk factors related with anxiety scores of children were also analyzed.ResultsTalking about the pandemic, concern about coronavirus transmission, taking precaution to prevent coronavirus transmission, making pressure to protect from COVID‐19 were significantly higher in parents within the study group (p < .05). Parents in the study group used more problem‐focused coping than parents in the control group (p = .003). Anxiety symptoms score was higher in children of the study group (p = .007). Parents in the study group found online education more useful than parents in the control group.ConclusionChildren with chronic lung diseases and their parents have more anxiety due to COVID‐19 pandemic and these parents use more mature coping strategies to manage the stress of the pandemic. Longitudinal and larger studies should be done in all aspects of online education in children with chronic lung diseases.
The clinical benefit of sequential therapy with androgen receptor axis‐targeted agents alone in patients with castration‐resistant prostate cancer: A propensity score‐matched comparison study
Authors: Naito Yushi , Kato Masashi , Kawanishi Hideji , Yuguchi Yuri , Yuba Takuma , Ishikawa Tomohiro , Hattori Kyosuke , Yamamoto Akiyuki , Sano Tomoyasu , Matsukawa Yoshihisa , Kimura Toru , Nishikimi Toshinori , Hattori Ryohei , Tsuzuki Toyonori , Gotoh Momokazu 
Published: September 2020

AbstractBackgroundThe optimal sequential therapy for castration‐resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis‐targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART‐to‐ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)‐combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC.MethodsWe retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first‐ or second‐line therapy after castration resistance. We compared the overall survival (OS) and the second progression‐free survival (PFS2), calculated from the initiation of first‐line therapy after castration resistance, between the AA sequence group and the DTX‐combined sequence group. PFS2 was defined as the period from the start of first‐line treatment after castration resistance to progression on second‐line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one‐to‐one nearest neighbor matching without replacement.ResultsOverall, 106 and 209 patients were administered the AA sequential therapy and DTX‐combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score‐matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68–1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX‐combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16–2.48; p = .007).ConclusionsCertain patients with CRPC can benefit from ART‐to‐ART sequential therapy in a daily clinical setting.
Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6
Authors: de Jong Jan , Mitselos Anna , Jurczak Wojciech , Cordoba Raul , Panizo Carlos , Wrobel Tomasz , Dlugosz‐Danecka Monika , Jiao James , Sukbuntherng Juthamas , Ouellet Daniele , Hellemans Peter 
Published: September 2020

AbstractIbrutinib may inhibit intestinal CYP3A4 and induce CYP2B6 and/or CYP3A. Secondary to potential induction, ibrutinib may reduce the exposure and effectiveness of oral contraceptives (OCs). This phase I study evaluated the effect of ibrutinib on the pharmacokinetics of the CYP2B6 substrate bupropion, CYP3A substrate midazolam, and OCs ethinylestradiol (EE) and levonorgestrel (LN). Female patients (N = 22) with B‐cell malignancies received single doses of EE/LN (30/150 μg) and bupropion/midazolam (75/2 mg) during a pretreatment phase on days 1 and 3, respectively (before starting ibrutinib on day 8), and again after ibrutinib 560 mg/day for ≥ 2 weeks. Intestinal CYP3A inhibition was assessed on day 8 (single‐dose ibrutinib plus single‐dose midazolam). Systemic induction was assessed at steady‐state on days 22 (EE/LN plus ibrutinib) and 24 (bupropion/midazolam plus ibrutinib). The geometric mean ratios (GMRs; test/reference) for maximum plasma concentration (Cmax) and area under the plasma concentration‐time curve (AUC) were derived using linear mixed‐effects models (90% confidence interval within 80%‐125% indicated no interaction). On day 8, the GMR for midazolam exposure with ibrutinib coadministration was ≤ 20% lower than the reference, indicating lack of intestinal CYP3A4 inhibition. At ibrutinib steady‐state, the Cmaxand AUC of EE were 33% higher than the reference, which was not considered clinically relevant. No substantial changes were noted for LN, midazolam, or bupropion. No unexpected safety findings were observed. A single dose of ibrutinib did not inhibit intestinal CYP3A4, and repeated administration did not induce CYP3A4/2B6, as assessed using EE, LN, midazolam, and bupropion.
Inverse Gaussian process model with frailty term in reliability analysis
Authors: Morita Lia H. M. , Tomazella Vera L. , Balakrishnan Narayanaswamy , Ramos Pedro L. , Ferreira Paulo H. , Louzada Francisco 
Published: September 2020

AbstractTraditional reliability analysis techniques focus on the occurrence of failures over time. Nevertheless, in certain cases where the occurrence of failures is tiny or almost null, the estimation of the quantities that describe the failure process is compromised. In this context, we introduce a reliability model for systems adopting the degradation process using frailty. The evolved degradation model has as experimental data, not the failure, but a quality feature attached to it. Degradation analysis can provide information about the lifetime distribution components without actually observing failures. In this paper, we propose an inverse Gaussian process model with frailty as a possible tool to investigate the effect of unobserved covariates. Moreover, a comparative study with the classical inverse Gaussian process based on simulated data was performed, revealing that the asymptotic properties of the maximum likelihood estimators are compromised when the presence of frailty is ignored. The application was based on two real data sets in the literature, showing that the inverse Gaussian process frailty models are propitious to use; however, gamma and inverse Gaussian distributions for frailty present similar results.
Vagueness and Care: On Affect and Literacy
Authors: Snaza Nathan 
Published: September 2020

AbstractIn this commentary, the author responds to three articles using affect studies to rethink literacy, in Reading Research Quarterly’s special issue on affect theory. Taking up how the three articles—by Boldt; Truman, Hackett, Pahl, Davies, and Escott; and Tanner, Leander, and Carter‐Stone—draw on divergent genealogies of affect theory, the author proposes that the ability of affect to capaciously capture such different approaches is one of its most important strengths. The author ends by considering the problem of borders as it appears across all three articles, ultimately arguing that the vagueness of concepts drawn from affect literacy is precisely what makes it an invaluable concept for thinking through how we may care for the literacies that sustain us.
Overexpression of alpha-1 antitrypsin in mesenchymal stromal cells improves their intrinsic biological properties and therapeutic effects in nonobese diabetic mice
Authors: Song Lili , Gou Wenyu , Wang Jingjing , Wei Hua , Lee Jennifer , Strange Charlie , Wang Hongjun 
Published: September 2020

AbstractIslet/β cell dysfunction and death caused by autoimmune-mediated injuries are major features of type 1 diabetes (T1D). Mesenchymal stromal cells (MSCs) have been used for the treatment of T1D in animal models and clinical trials. Based on the anti-inflammatory effects of alpha-1 antitrypsin (AAT), we generated human AAT engineered MSCs (hAAT-MSCs) by infecting human bone marrow-derived MSCs with the pHAGE CMV-a1aT-UBC-GFP-W lentiviral vector. We compared the colony forming, differentiation, and migration capacity of empty virus-treated MSCs (hMSC) and hAAT-MSCs and tested their protective effects in the prevention of onset of T1D in nonobese diabetic (NOD) mice. hAAT-MSCs showed increased self-renewal, better migration and multilineage differentiation abilities compared to hMSCs. In addition, polymerase chain reaction array for 84 MSC-related genes showed that 23 genes were upregulated, and 3 genes were downregulated in hAAT-MSCs compared to hMSCs. Upregulated genes include those critical for the stemness (ie, Wnt family member 3A [WNT3A], kinase insert domain receptor [KDR]), migration (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion protein 1 [VICAM-1], matrix metalloproteinase-2 [MMP2]), and survival (insulin-like growth factor 1 [IGF-1]) of MSCs. Pathway analysis showed that changed genes were related to growth factor activity, positive regulation of cell migration, and positive regulation of transcription. In vivo, a single intravenous infusion of hAAT-MSCs significantly limited inflammatory infiltration into islets and delayed diabetes onset in the NOD mice compared with those receiving vehicle or hMSCs. Taken together, overexpression of hAAT in MSCs improved intrinsic biological properties of MSCs needed for cellular therapy for the treatment of T1D.