bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analisis Nilai dan Keterbacaan Kisah Rasulullah sebagai Sumber Bacaan Mata Pelajaran Bahasa Indonesia
Authors: Ariffiando Nady Febri 
Published: July 2021

The use of text with character content in learning is one of the efforts to strengthen children's moral kognition which is one of the keys to ordering characters. This study aimed to analyze the character values contained in the story of Rasulullah and test the readability of the story. The results of the value analysis by were validated by value education experts, language education experts in elementary schools and hadis experts. Researchers conducted a readability test using Raygor and fry graph. The results show that there are five stories that contained the main values of social care and the accompaniment values of patience, empathy and generosity. The readability test results show that the five stories are suitable for reading by children aged 1o to 12 years. From these results, the story of the Prophet is right for use in literary learning with the aim of instilling character.
Indispensable Role of HIF-1α Signaling in Post-implantation Survival and Angio-/Vasculogenic Properties of SHED
Authors: Han Yuanyuan , Chen Qixin , Zhang Lili , Dissanayaka Waruna Lakmal 
Published: July 2021

ObjectivesPost-implantation survival and timely vascularization of stem-cell based constructs are critical factors in achieving successful outcomes in tissue regeneration approaches. Hypoxia inducible factor-1α (HIF-1α) is known to mediate adaptive functions to ischemic stress in many different cell types. The current study aimed to explore the role of HIF-1α in post-implantation survival and angio-/vasculogenesis of stem cells from human exfoliated deciduous teeth (SHED).MethodsHIF-1α in SHED was suppressed using siRNA or chemical inhibitor (YC-1) and used in Matrigel plug assay conducted on severe combined immunodeficient mice. The plugs were retrieved on day 3 or 7 post-injection and analyzed for hypoxia status, ki67 expression, DNA fragmentation (TUNEL), cellularity, and vascularization by histology and immunohistochemistry for CD31, HIF-1α, pyruvate dehydrogenase kinase-1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (Glut1). Cell viability of HIF-1α silenced SHED under different stress conditions (hypoxia, H2O2, and low glucose) in vitro was measured by CCK-8 assay. CM-H2DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS) levels, respectively. PDK1, HK2, and Glut1 expression were measured by western blotting and immunofluorescence. Secretory protein levels of vascular endothelial growth factor (VEGF) and the respective paracrine effects on endothelial cell proliferation and migration were detected by ELISA, CCK-8 assay, and trans-well assay, respectively.ResultsHistological analysis of Matrigel plugs showed significantly reduced cell survival in HIF-1α silenced or chemically inhibited SHED groups, which could be attributed to diminished metabolic adaptations as shown by decreased PDK1, HK2, and Glut1 expression. HIF-1α inhibition in SHED also resulted in significantly low blood vessel formation as observed by a low number of perfused and non-perfused vessels of human or mouse CD31 origin. The viability of HIF-1α silenced SHED was significantly affected under hypoxia, H2O2, and low-glucose conditions in vitro, which was reflected in increased cytoplasmic and mitochondrial ROS levels. Significantly reduced levels of VEGF in HIF-1α silenced SHED resulted in decreased paracrine angiogenic effects as shown by low proliferation and migration of endothelial cells.ConclusionHIF-1α plays an indispensable role in post-implantation survival and angio-/vasculogenic properties of SHED by maintaining ROS homeostasis, inducing metabolic adaptations, and VEGF secretion.
Pharmacological Targeting of BMP6-SMAD Mediated Hepcidin Expression Does Not Improve the Outcome of Systemic Infections With Intra-Or Extracellular Gram-Negative Bacteria in Mice
Authors: Hoffmann Alexander , de Souza Lara Valente , Seifert Markus , von Raffay Laura , Haschka David , Grubwieser Philipp , Grander Manuel , Mitterstiller Anna-Maria , Nairz Manfred , Poli Maura , Weiss Günter 
Published: July 2021

IntroductionHepcidin is the systemic master regulator of iron metabolism as it degrades the cellular iron exporter ferroportin. In bacterial infections, hepcidin is upregulated to limit circulating iron for pathogens, thereby increasing iron retention in macrophages. This mechanism withholds iron from extracellular bacteria but could be of disadvantage in infections with intracellular bacteria. We aimed to understand the role of hepcidin in infections with intra- or extracellular bacteria using different hepcidin inhibitors.MethodsFor the experiments LDN-193189 and oversulfated heparins were used, which interact with the BMP6-SMAD pathway thereby inhibiting hepcidin expression. We infected male C57BL/6N mice with either the intracellular bacteriumSalmonellaTyphimurium or the extracellular bacteriumEscherichia coliand treated these mice with the different hepcidin inhibitors.ResultsBoth inhibitors effectively reduced hepcidin levelsin vitrounder steady state conditions and upon stimulation with the inflammatory signals interleukin-6 or lipopolysaccharide. The inhibitors also reduced hepcidin levels and increased circulating iron concentration in uninfected mice. However, both compounds failed to decrease liver- and circulating hepcidin levels in infected mice and did not affect ferroportin expression in the spleen or impact on serum iron levels. Accordingly, both BMP-SMAD signaling inhibitors did not influence bacterial numbers in different organs in the course ofE.colior S.Tm sepsis.ConclusionThese data indicate that targeting the BMP receptor or the BMP-SMAD pathway is not sufficient to suppress hepcidin expression in the course of infection with both intra- or extracellular bacteria. This suggests that upon pharmacological inhibition of the central SMAD-BMP pathways during infection, other signaling cascades are compensatorily induced to ensure sufficient hepcidin formation and iron restriction to circulating microbes.
Thermokarst Lagoons: A Core-Based Assessment of Depositional Characteristics and an Estimate of Carbon Pools on the Bykovsky Peninsula
Authors: Jenrich Maren , Angelopoulos Michael , Grosse Guido , Overduin Pier Paul , Schirrmeister Lutz , Nitze Ingmar , Biskaborn Boris K. , Liebner Susanne , Grigoriev Mikhail , Murray Andrew , Jongejans Loeka L. , Strauss Jens 
Published: July 2021

Permafrost region subsurface organic carbon (OC) pools are a major component of the terrestrial carbon cycle and vulnerable to a warming climate. Thermokarst lagoons are an important transition stage with complex depositional histories during which permafrost and lacustrine carbon pools are transformed along eroding Arctic coasts. The effects of temperature and salinity changes during thermokarst lake to lagoon transitions on thaw history and lagoon deposits are understudied. We analyzed two 30-m-long sediment cores from two thermokarst lagoons on the Bykovsky Peninsula, Northeast Siberia, using sedimentological, geochronological, hydrochemical, and biogeochemical techniques. Using remote sensing we distinguished between a semi-closed and a nearly closed lagoon. We (1) characterized the depositional history, (2) studied the impact of marine inundation on ice-bearing permafrost and taliks, and (3) quantified the OC pools for different stages of thermokarst lagoons. Fluvial and former Yedoma deposits were found at depth between 30 and 8.5 m, while lake and lagoon deposits formed the upper layers. The electrical conductivity of the pore water indicated hypersaline conditions for the semi-closed lagoon (max: 108 mS/cm), while fresh to brackish conditions were observed beneath a 5 m-thick surface saline layer at the nearly closed lagoon. The deposits had a mean OC content of 15 ± 2 kg/m3, with higher values in the semi-closed lagoon. Based on the cores we estimated a total OC pool of 5.7 Mt-C for the first 30 m of sediment below five mapped lagoons on the Bykovsky Peninsula. Our results suggest that paleo river branches shaped the middle Pleistocene landscape followed by late Pleistocene Yedoma permafrost accumulation and early Holocene lake development. Afterward, lake drainage, marine flooding, and bedfast ice formation caused the saline enrichment of pore water, which led to cryotic talik development. We find that the OC-pool of Arctic lagoons may comprise a substantial inventory of partially thawed and partially refrozen OC, which is available for microbial degradation processes at the Arctic terrestrial-marine interface. Climate change in the Arctic leading to sea level rise, permafrost thaw, coastal erosion, and sea ice loss may increase the rate of thermokarst lagoon formation and thus increase the importance of lagoons as biogeochemical processors of former permafrost OC.
Reconstruction of the Upper Slope Conditions of an Extraordinary Hydro-Meteorological Event Along the Jamapa Glacier Drainage System, Citlaltépetl (Pico de Orizaba) Volcano, Mexico
Authors: Sieron Katrin , Weissling Blake , Morales-Martínez Marco Aurelio , Teran Sergio 
Published: July 2021

A singular precipitation event on the summit glacial slopes of Mexico’s highest volcanic peak, Citlatépetl (also known as Pico de Orizaba), associated with the passage of Hurricane Ernesto across the southern Mexico mainland in August 2012, resulted in a debris flow at altitudes above 4,400 m asl, culminating in a hyperconcentrated flow downstream that had major impacts to a river valley’s channel morphology as well as to communities along a 25 km runout. The lahar originated at the terminal moraine and proglacial ramp of the Little Ice Age (LIA) extent of Citlaltépetl’s Jamapa glacier. Precipitation amounts were estimated based on nearby CONAGUA stations, but also on TRMM satellite images leading to an estimated 106 mm for a 3 day total, with 85 mm (80% of the total) falling on August 9th, the date when the lahar event occurred. The initial debris flow removed a minimum estimated 60,000 m3 of material from the proglacial ramp. A possible causative scenario is that the precipitation event overpressured the groundwater hydrology of an already unstable glacial-melt-saturated moraine. We demonstrate a methodology for the recreation of a pre-event landscape and the environmental conditions at the onset of the lahar, utilizing satellite products, in-situ geomorphological and geological evidence, and UAS technology.
An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent
Authors: Skirecki Tomasz , Drechsler Susanne , Jeznach Aldona , Hoser Grażyna , Jafarmadar Mohammad , Kawiak Jerzy , Osuchowski Marcin F. 
Published: July 2021

Adult hematopoietic stem and progenitor cells (HSPCs) respond to bacterial infections by expansion to myeloid cells. Sepsis impairs this process by suppressing differentiation of stem cells subsequently contributing to an ineffective immune response. Whether the magnitude of HSPCs impairment in sepsis is severity-dependent remains unknown. This study investigated dynamics of the HSPC immune-inflammatory response in the bone marrow, splenic, and blood compartments in moribund and surviving septic mice. The 12-week-old outbred CD-1 female mice (n=65) were subjected to a cecal ligation and puncture (CLP) sepsis, treated with antibiotics and fluid resuscitation, and stratified into predicted-to-die (P-DIE) and predicted-to-survive (P-SUR) cohorts for analysis. CLP strongly reduced the common myeloid and multipotent progenitors, short- and long-term hematopoietic stem cell (HSC) counts in the bone marrow; lineage−ckit+Sca-1+ and short-term HSC suppression was greater in P-DIE versus P-SUR mice. A profound depletion of the common myeloid progenitors occurred in the blood (by 75%) and spleen (by 77%) of P-DIE. In P-SUR, most common circulating HSPCs subpopulations recovered to baseline by 72 h post-CLP. Analysis of activated caspase-1/-3/-7 revealed an increased apoptotic (by 30%) but not pyroptotic signaling in the bone marrow HSCs of P-DIE mice. The bone marrow from P-DIE mice revealed spikes of IL-6 (by 5-fold), CXCL1/KC (15-fold), CCL3/MIP-1α (1.7-fold), and CCL2/MCP-1 (2.8-fold) versus P-SUR and control (TNF, IFN-γ, IL-1β, -5, -10 remained unaltered). Summarizing, our findings demonstrate that an early sepsis-induced impairment of myelopoiesis is strongly outcome-dependent but varies among compartments. It is suggestive that the HSCPC loss is at least partly due to an increased apoptosis but not pyroptosis.
“Patient Comfort Can Be Sacrificed for Patient Safety”—Perception and Practice Reported by Critical Care Nurses Toward Physical Restraints: A Qualitative Descriptive Study
Authors: Cui Nianqi , Qiu Ruolin , Zhang Yuping , Jin Jingfen 
Published: July 2021

Aim: The aim of the study was to explore the perception and practice of physical restraints used by critical care nurses.Design: A qualitative descriptive design was used.Method: From December 2019 to May 2020, a one-to-one, semi-structured in-depth interview with 10 critical care nurses from two intensive care units in a tertiary general hospital with 3,200 beds in China was conducted using the method of purposeful sampling. The data were analyzed using inductive thematic analysis.Findings: The perception of physical restraints among critical care nurses was that patient comfort can be sacrificed for patient safety. Physical restraints protected patient safety by preventing patients from unplanned extubation but influenced patient comfort. Physical restraints were common practice of critical care nurses. Relative physical restraints provided patients with more freedom of movement and rationalization of physical restraints which were the practical strategies.Conclusion: The study identified problems in critical care nurses' perception and practice on physical restraints. Critical care nurses are confident that physical restraints can protect patient safety, and the influence of physical restraints on patient comfort is just like the side effect. Although physical restraints were common practice, critical care nurses still faced dilemmas in the implementation of physical restraints. Relative physical restraints and rationalization of physical restraints help critical care nurses cope with the “bad feelings,” which may also be the cause of unplanned extubation. It is necessary for the adaptation of clinical practice guidelines about physical restraints for critically ill patients in the Chinese context, to change the perception and practice of critical care nurses and deliver safe and high-quality patient care.
LncRNA ENSMUST00000155383 is Involved in the Improvement of DPP-4 Inhibitor MK-626 on Vascular Endothelial Function by Modulating Cacna1c-Mediated Ca2+ Influx in Hypertensive Mice
Authors: Zhang Yi , Tan Na , Zong Yi , Li Li , Zhang Yan , Liu Jian , Wang Xiaorui , Han Wenwen , Liu Limei 
Published: July 2021

Objective: This study investigated the protective effects of dipeptidyl peptidase-4 inhibitor MK-626 on vascular endothelial function by regulating lncRNAs in hypertensive vasculature.Methods: Angiotensin Ⅱ (Ang Ⅱ)-loaded osmotic pumps were implanted in mice with or without MK-626 administration. GLP-1 levels in plasma were measured by ELISA. Aortic rings were suspended in myograph for tension measurement. Microarray was performed to analyze lncRNA and mRNA expression profiles. Protein expression and phosphorylation were examined by Western blot. The differentially expressed (DE)-genes were validated by qRT-PCR. The intracellular Ca2+ concentration was detected by laser confocal system.Results: MK-626 elevated plasma GLP-1 level, increased eNOS phosphorylation, improved endothelium-dependent relaxations, and reduced systolic blood pressure in Ang Ⅱ-induced hypertensive mice. Microarray revealed the dysregulations of 723 lncRNAs and 742 mRNAs were reversed by MK-626 in hypertensive mouse aortae. qRT-PCR validation showed that 13 DE-lncRNAs and eight dysregulated mRNAs in both hypertensive mouse aortae and mouse aortic endothelial cells (MAECs) were rescued by MK-626. Among them, four mRNAs (Cacna1C, Itgav, Itga8, and Npnt) were co-expressed with lncRNA ENSMUST00000155383. Cacna1C protein expression was reduced in the ECs but was elevated in smooth muscle cells from Ang Ⅱ-infused mice, which were both reversed by MK-626. Knockdown of lncRNA ENSMUST00000155383 suppressed the increased Cacna1c protein and mRNA expression, elevated Ca2+ level, and enhanced eNOS phosphorylation induced by MK-626 in the hypertensive mouse ECs.Conclusion: The dysregulations of lncRNA ENSMUST00000155383-associated genes might play crucial roles in hypertension-induced endothelial dysfunction through affecting calcium pathway. MK-626 might ameliorate endothelial dysfunction by upregulating lncRNA ENSMUST00000155383, enhancing Ca2+ concentration, and subsequently restoring eNOS activity in hypertension.
An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms
Authors: Soerensen Sofie Forsberg , Wirenfeldt Martin , Wlodarczyk Agnieszka , Moerch Marlene Thorsen , Khorooshi Reza , Arengoth Dina S. , Lillevang Soeren Thue , Owens Trevor , Asgari Nasrin 
Published: July 2021

Background: Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms.Objective: To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 [aquaporin-4 (AQP4)-immunoglobulin G (AQP4-IgG)] in the optic nerve.Materials and Methods: Purified IgG from an AQP4-IgG-positive NMOSD-ON patient was together with human complement (C) given to wild-type (WT) and type I interferon (IFN) receptor-deficient mice (IFNAR1-KO) as two consecutive intrathecal injections into cerebrospinal fluid via cisterna magna. The optic nerves were isolated, embedded in paraffin, cut for histological examination, and scored semi-quantitatively in a blinded fashion. In addition, optic nerves were processed to determine selected gene expression by quantitative real-time PCR.Results: Intrathecal injection of AQP4-IgG+C induced astrocyte pathology in the optic nerve with loss of staining for AQP4 and glial fibrillary acidic protein (GFAP), deposition of C, and demyelination, as well as upregulation of gene expression for interferon regulatory factor-7 (IRF7) and CXCL10. Such pathology was not seen in IFNAR1-KO mice nor in control mice.Conclusion: We describe induction of ON in an animal model for NMOSD and show a requirement for type I IFN signaling in the disease process.
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center
Authors: Quaas Alexander , Rehkaemper Jan , Rueschoff Josef , Pamuk Aylin , Zander Thomas , Hillmer Axel , Siemanowski Janna , Wittig Jana , Buettner Reinhard , Plum Patrick , Popp Felix , Gebauer Florian , Bruns Christiane Josephine , Loeser Heike , Alakus Hakan , Schoemig-Markiefka Birgid 
Published: July 2021

IntroductionKnowledge of the high microsatellite-instability (MSI-H)/mismatch repair deficiency (MMRd) status is of increasing interest for personalized neoadjuvant or adjuvant therapy planning. Only a few studies are available on MSI-H distribution in the Northern European Caucasian patient population. In this study, we focused on a large cohort of tumors of the upper gastrointestinal tract.Materials and MethodsSurgical material from a total of 1,965 patients was analyzed for MSI-H/MMRd status (including 1,267 carcinomas of the esophagus or stomach). All tumors were analyzed with an internationally recommended immunohistochemical panel consisting of four antibodies (MLH1, MSH2, PMS2, and MSH6). The results were molecularly objectified.ResultsAdenocarcinomas with MSI-H/MMRd were detected with the following distribution: esophagus (1.4%), stomach (8.3%), small intestine (18.2%), large intestine (8.5%), intrahepatic bile ducts (1.9%), and pancreas (0%). In case of gastric tumors with MSI-H/MMRd, neoadjuvant therapy did not influence the prognosis of patients (p = 0.94). Within all tumor entities with MSI-H/MMRd, patients with a UICC stage 4 were also represented. In this advanced stage, 11.7% of patients with MSS tumors were diagnosed compared to 0.5% of patients with MSI-H tumors relative to the entire tumor collective.DiscussionIn this study, the proportion of MSI-H/MMRd tumors in the stomach is smaller than would have been expected in knowledge of the data published by TCGA or AGRC. Negative prognostic effects regarding MSI-H status and neoadjuvant therapy as described by the MAGIC study group were not seen in our cohort. The extent to which the MSI-H/MMRd status should be known for neoadjuvant therapy planning must be clarified in prospective studies in the future. At present, there is no convincing data to dispense the neoadjuvant therapy for gastric carcinoma. Due to the very convincing, positive data regarding the response rates of MSI-H tumors to treatment with PD1/PD-L1 inhibitors, every metastatic carcinoma of the gastrointestinal tract should be tested for its MSI-H status.
Meta-Analysis of HER2-Enriched Subtype Predicting the Pathological Complete Response Within HER2-Positive Breast Cancer in Patients Who Received Neoadjuvant Treatment
Authors: Shen Guoshuang , Zhao Fuxing , Huo Xingfa , Ren Dengfeng , Du Feng , Zheng Fangchao , Zhao Jiuda 
Published: July 2021

BackgroundThis meta-analysis aimed to better elucidate the predictive value of human epidermal growth factor receptor 2 (HER2)-enriched subtype of pathological complete response (pCR) rate within HER2-positive breast cancer patients receiving neoadjuvant treatment.MethodsWe identified prospective trials that evaluated the correlation between an HER2-enriched subtype and pCR rate in HER2-positive breast cancer. Pooled odds ratio (OR) values with 95% confidence intervals (CIs) were computed.ResultsFifteen studies comprising 2,190 patients met the inclusion criteria. The HER2-enriched subtype was associated with increased odds of achieving a pCR (OR = 4.12, 95% CI = 3.38 to 5.03, P &lt; 0.001) in patients overall. Moreover, it was correlated with improved pCR when single or dual HER2-targeted agent-based therapy was employed (OR = 3.36, 95% CI = 2.25 to 5.02, P &lt; 0.001; OR = 4.66, 95% CI = 3.56 to 6.10, P &lt; 0.001, respectively), but not when HER2-targeted agent-free chemotherapy was used (OR = 2.52, 95% CI = 0.98 to 6.49, P = 0.05). Moreover, an HER2-enriched subtype predicted higher pCR rates irrespective of HER2-targeted agents (trastuzumab, lapatinib, pertuzumab, or T-DM1); chemotherapy agents (taxane-based, or anthracyclines plus taxane-based); endocrine therapy and hormone receptor [all the differences were statistically significant (P all ≤ 0.001)].ConclusionsThe HER2-enriched subtype can more effectively and specifically predict pCR for HER2-targeted agent-based neoadjuvant treatment, irrespective of the number (single or dual) or category of HER2-targeted agent, including chemotherapy and endocrine therapy, or hormone receptor in cases of HER2-positive breast cancer.