bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking microbial Sphagnum degradation and acetate mineralization in acidic peat bogs: from global insights to a genome-centric case study
Authors: St James Andrew R , Yavitt Joseph B , Zinder Stephen H , Richardson Ruth E 
Published: September 2020

Abstract
Ombrotrophic bogs accumulate large stores of soil carbon that eventually decompose to carbon dioxide and methane. Carbon accumulates because Sphagnum mosses slow microbial carbon decomposition processes, leading to the production of labile intermediate compounds. Acetate is a major product of Sphagnum degradation, yet rates of hydrogenotrophic methanogenesis far exceed rates of aceticlastic methanogenesis, suggesting that alternative acetate mineralization processes exist. Two possible explanations are aerobic respiration and anaerobic respiration via humic acids as electron acceptors. While these processes have been widely observed, microbial community interactions linking Sphagnum degradation and acetate mineralization remain cryptic. In this work, we use ordination and network analysis of functional genes from 110 globally distributed peatland metagenomes to identify conserved metabolic pathways in Sphagnum bogs. We then use metagenome-assembled genomes (MAGs) from McLean Bog, a Sphagnum bog in New York State, as a local case study to reconstruct pathways of Sphagnum degradation and acetate mineralization. We describe metabolically flexible Acidobacteriota MAGs that contain all genes to completely degrade Sphagnum cell wall sugars under both aerobic and anaerobic conditions. Finally, we propose a hypothetical model of acetate oxidation driven by changes in peat redox potential that explain how bogs may circumvent aceticlastic methanogenesis through aerobic and humics-driven respiration.
(+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis
Authors: Wang Min , Liu Chun-Yu , Wang Tian , Yu Hong-Min , Ouyang Shu-Hua , Wu Yan-Ping , Gong Hai-Biao , Ma Xiao-Hui , Jiao Gen-Long , Fu Lei-Lei , Wu Qiong-Shi , Kurihara Hiroshi , Li Yi-Fang , Shen Tao , He Rong-Rong 
Published: September 2020

AbstractDrug-induced liver injury is the major cause of acute liver failure. However, the underlying mechanisms seem to be multifaceted and remain poorly understood, resulting in few effective therapies. Here, we report a novel mechanism that contributes to acetaminophen-induced hepatotoxicity through the induction of ferroptosis, a distinctive form of programmed cell death. We subsequently identified therapies protective against acetaminophen-induced liver damage and found that (+)-clausenamide ((+)-CLA), an active alkaloid isolated from the leaves of Clausena lansium (Lour.) Skeels, inhibited acetaminophen-induced hepatocyte ferroptosis both in vivo and in vitro. Consistently, (+)-CLA significantly alleviated acetaminophen-induced or erastin-induced hepatic pathological damages, hepatic dysfunctions and excessive production of lipid peroxidation both in cultured hepatic cell lines and mouse liver. Furthermore, treatment with (+)-CLA reduced the mRNA level of prostaglandin endoperoxide synthase 2 while it increased the protein level of glutathione peroxidase 4 in hepatocytes and mouse liver, confirming that the inhibition of ferroptosis contributes to the protective effect of (+)-CLA on drug-induced liver damage. We further revealed that (+)-CLA specifically reacted with the Cys-151 residue of Keap1, which blocked Nrf2 ubiquitylation and resulted in an increased Nrf2 stability, thereby leading to the activation of the Keap1–Nrf2 pathway to prevent drug-induced hepatocyte ferroptosis. Our studies illustrate the innovative mechanisms of acetaminophen-induced liver damage and present a novel intervention strategy to treat drug overdose by using (+)-CLA.
Immune signature driven by ADT-induced immune microenvironment remodeling in prostate cancer is correlated with recurrence-free survival and immune infiltration
Authors: Long Xingbo , Hou Huimin , Wang Xuan , Liu Shengjie , Diao Tongxiang , Lai Shicong , Hu Maolin , Zhang Shengqi , Liu Ming , Zhang Hong 
Published: September 2020

AbstractAndrogen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear. To explore the effects of ADT on PCa TIM, RNA sequencing was performed on six paired pre-ADT biopsy and post-ADT PCa lesions, and five paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa. Bioinformatics methods including ESTIMATE and ssGSEA were used to evaluate the stromal immune score and immune cell infiltration in PCa and paracancerous tissues. Weighted correlation network analysis was used to screen hub genes in the ADT-induced immune remodeling process. The results showed differences exist between PCa and paracancerous tissues in response to ADT. Compared with paracancerous tissues, the immune remodeling effect of ADT in PCa was more intense. ZFP36, JUNB, and SOCS3 served as hub genes in the ADT-induced immune remodeling process and were associated with PSA recurrent-free survival in the TCGA and our neoadjuvant ADT cohort. To investigate the joint action of the above three hub genes, an immune signature score was constructed. The results showed that immune signature score-based immune subtypes reveal the heterogeneity of the immune microenvironment of PCa and showed significant differences in patient prognosis, tumor immune infiltration, mutation burden, and landscape.
Crosstalk between cardiomyocytes and noncardiomyocytes is essential to prevent cardiomyocyte apoptosis induced by proteasome inhibition
Authors: Guo Fang , Zhang Chen-Chen , Yin Xi-Hui , Li Ting , Fang Cheng-Hu , He Xi-Biao 
Published: September 2020

AbstractHeart is a multi-cellular organ made up of various cell types interacting with each other. Cardiomyocytes may benefit or suffer from crosstalk with noncardiomyocytes in response to diverse kinds of cardiac stresses. Proteasome dysfunction is a common cardiac stress which causes cardiac proteotoxicity and contributes to cardiac diseases such as heart failure and myocardial infarction. The role of crosstalk between cardiomyocytes and noncardiomyocytes in defense of cardiac proteotoxicity remains unknown. Here, we report a cardiomyocyte-specific survival upon proteasome inhibition in a heterogeneous culture consisting of cardiomyocytes and other three major cardiac cell types. Conversely, cardiomyocyte apoptosis is remarkably induced by proteasome inhibition in a homogeneous culture consisting of a majority of cardiomyocytes, demonstrating an indispensable role of noncardiomyocytes in the prevention of cardiomyocyte apoptosis resulting from proteasome inhibition. We further show that cardiomyocytes express brain natriuretic peptide (BNP) as an extracellular molecule in response to proteasome inhibition. Blockade of BNP receptor on noncardiomyocytes significantly exacerbated the cardiomyocyte apoptosis, indicating a paracrine function of cardiomyocyte-released extracellular BNP in activation of a protective feedback from noncardiomyocytes. Finally, we demonstrate that proteasome inhibition-activated transcriptional up-regulation of BNP in cardiomyocytes was associated with the dissociation of repressor element 1 silencing transcription factor (REST)/ histone deacetylase 1 (HDAC1) repressor complex from BNP gene promoter. Consistently, the induction of BNP could be further augmented by the treatment of HDAC inhibitors. We conclude that the crosstalk between cardiomyocytes and noncardiomyocytes plays a crucial role in the protection of cardiomyocytes from proteotoxicity stress, and identify cardiomyocyte-released BNP as a novel paracrine signaling molecule mediating this crosstalk. These findings provide new insights into the key regulators and cardioprotective mechanism in proteasome dysfunction-related cardiac diseases.
Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway
Authors: Zhang Jing , Wu Linhui , Lian Chaoqun , Lian Shuo , Bao Shimeng , Zhang Jisheng , Wang Peter , Ma Jia , Li Yuyun 
Published: September 2020

AbstractNitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.
A reporter for noninvasively monitoring gene expression and plant transformation
Authors: He Yubing , Zhang Tao , Sun Hui , Zhan Huadong , Zhao Yunde 
Published: September 2020

AbstractReporters have been widely used to visualize gene expression, protein localization, and other cellular activities, but the commonly used reporters require special equipment, expensive chemicals, or invasive treatments. Here, we construct a new reporter RUBY that converts tyrosine to vividly red betalain, which is clearly visible to naked eyes without the need of using special equipment or chemical treatments. We show that RUBY can be used to noninvasively monitor gene expression in plants. Furthermore, we show that RUBY is an effective selection marker for transformation events in both rice and Arabidopsis. The new reporter will be especially useful for monitoring cellular activities in large crop plants such as a fruit tree under field conditions and for observing transformation and gene expression in tissue culture under sterile conditions.
The effects of driving time scales on heating in a coronal arcade
Authors: Howson T. A. , De Moortel I. , Fyfe L. E. 
Published: September 2020

Context. The relative importance of alternating current (AC) and direct current (DC) heating mechanisms in maintaining the temperature of the solar corona is not well constrained.
Aims. We aim to investigate the effects of the characteristic time scales of photospheric driving on the injection and dissipation of magnetic and kinetic energy within a coronal arcade.
Methods. We conducted three-dimensional magnetohydrodynamic simulations of complex foot point driving imposed on a potential coronal arcade. We modified the typical time scales associated with the velocity driver to understand the efficiency of heating obtained using AC and DC drivers. We considered the implications for the injected Poynting flux and the spatial and temporal nature of the energy release in dissipative regimes.
Results. For the same driver amplitude and complexity, long time scale velocity motions are able to inject a much greater Poynting flux of energy into the corona. Consequently, in non-ideal regimes, slow stressing motions result in a greater increase in plasma temperature than for wave-like driving. In dissipative simulations, Ohmic heating is found to be much more significant than viscous heating. For all drivers in our parameter space, energy dissipation is greatest close to the base of the arcade, where the magnetic field strength is strongest, and at separatrix surfaces, where the field connectivity changes. Across all simulations, the background field is stressed with random foot point motions (in a manner more typical of DC heating studies), and, even for short time scale driving, the injected Poynting flux is large given the small amplitude flows considered. For long time scale driving, the rate of energy injection was comparable to the expected requirements in active regions. The heating rates were found to scale with the perturbed magnetic field strength and not the total field strength.
Conclusions. Alongside recent studies that show that power within the corona is dominated by low frequency motions, our results suggest that, in the closed corona, DC heating is more significant than AC heating.
Central discontinuous Galerkin methods on overlapping meshes for wave equations
Authors: Liu Yong , Lu Jianfang , Shu Chi-Wang , Zhang Mengping 
Published: September 2020

In this paper, we study the central discontinuous Galerkin (DG) method on overlapping meshes for second order wave equations. We consider the first order hyperbolic system, which is equivalent to the second order scalar equation, and construct the corresponding central DG scheme. We then provide the stability analysis and the optimal error estimates for the proposed central DG scheme for one- and multi-dimensional cases with piecewise Pk elements. The optimal error estimates are valid for uniform Cartesian meshes and polynomials of arbitrary degree k ≥ 0. In particular, we adopt the techniques in Liu et al. (SIAM J. Numer. Anal. 56 (2018) 520–541; ESAIM: M2AN 54 (2020) 705–726) and obtain the local projection that is crucial in deriving the optimal order of convergence. The construction of the projection here is more challenging since the unknowns are highly coupled in the proposed scheme. Dispersion analysis is performed on the proposed scheme for one dimensional problems, indicating that the numerical solution with P1 elements reaches its minimum with a suitable parameter in the dissipation term. Several numerical examples including accuracy tests and long time simulation are presented to validate the theoretical results.
Interventionelle Therapien zur Behandlung der hochgradigen Trikuspidalklappeninsuffizienz
Authors: Löw Kornelia , Hausleiter Jörg , Braun Daniel 
Published: September 2020

ZUSAMMENFASSUNGDie Trikuspidalklappeninsuffizienz stellt eine häufige Manifestation valvulärer Herzerkrankungen dar, die sich in Abhängigkeit der Ätiologie in eine primäre und eine sekundäre Form unterteilen lässt und mit einer erhöhten Mortalität assoziiert ist. Aufgrund eines multimorbiden Patientenkollektivs und eines damit einhergehenden hohen operativen Risikos ist jedoch das in den Leitlinien empfohlene operative Vorgehen in vielen Fällen nicht umsetzbar. In den letzten Jahren wurden verschiedene interventionelle Therapieverfahren entwickelt, die 3 unterschiedliche Ansätze verfolgen: 1. Annuloplastiesysteme imitieren das chirurgische Verfahren der Ringannuloplastie mittels Raffung des Trikuspidalklappenannulus. 2. Koapationssysteme wie beispielsweise Edge-to-Edge-Verfahren bewirken eine Verringerung der Regurgitation durch Verkleinerung der Koaptationslücke auf Ebene der Klappensegel. 3. Heterotope Klappen fungieren als in die Vena cava inferior und superior eingesetzte Ventile und sollen den venösen Rückfluss in den Körperkreislauf reduzieren.
Kathetergestützte Aortenklappenimplantation
Authors: Seiffert Moritz , Ensminger Stephan 
Published: September 2020

ZUSAMMENFASSUNGDie kathetergestützte Behandlung hat sich bei Patienten unterschiedlicher Risikoprofile mit hochgradiger symptomatischer Aortenklappenstenose als ein sehr sicheres Verfahren mit guten funktionellen Ergebnissen etabliert und ist für viele Patienten zur Behandlung der Wahl geworden. Insbesondere bei Patienten mit niedrigem operativem Risiko zeigten sich im kurzfristigen Verlauf einige Vorteile gegenüber dem operativen Aortenklappenersatz. Allerdings fielen in der mittelfristigen Nachbeobachtung kürzlich erstmals erhöhte Ereignisraten des kathetergestützten Verfahrens auf. Bei limitierten Daten zur Langzeit-Haltbarkeit der Transkatheter-Herzklappenprothesen steht insbesondere bei jüngeren Patienten die ausgewogene Diskussion der Therapieoptionen im interdisziplinären Heart Team mit dem Ziel eineslangfristigen Behandlungsplans im Vordergrund.
Kathetergestützter Mitralklappenersatz
Authors: Conradi Lenard , Lubos Edith 
Published: September 2020

ZUSAMMENFASSUNGDie Behandlung der unterschiedlichen Formen der Mitralklappeninsuffizienz beruht gemäß aktuell geltender Leitlinien auf der Mitralklappenchirurgie, der kathetergestützten endovaskulären Edge-to-Edge-Therapie und einer medikamentösen, sowie in manchen Fällen der sekundären Mitralklappeninsuffizienz „device-basierten“ Herzinsuffizienztherapie. Derzeit gilt es, aus den bisherigen und zukünftigen Therapieoptionen ein maßgeschneidertes Konzept für die verschiedenen pathophysiologischen Varianten der Mitralklappeninsuffizienz zu etablieren. Neben diesen Konzepten haben in der jüngeren Vergangenheit Verfahren zum kathetergestützten Mitralklappenersatz („transcatheter mitral valve implantation“, TMVI) große Aufmerksamkeit erlangt. Diese Verfahren sind prinzipiell sowohl in chirurgisch-transapikaler als auch in endovaskulärer, transvenös-transseptaler Technik verfügbar.
Operative Mitralklappenrekonstruktion
Authors: Hamiko Marwan , Treede Hendrik , Reichenspurner Hermann 
Published: September 2020

ZUSAMMENFASSUNGDie Mitralklappeninsuffizienz (MI) gehört neben der Aortenklappenstenose zu den häufigsten Klappenfehlern in den westlichen Ländern. Man unterscheidet je nach Pathologie zwischen der primären (degenerativen) und der sekundären (funktionellen) MI. Für die degenerative MI ist der therapeutische Goldstandard die chirurgisch-klappenerhaltende Korrektur des entsprechenden Klappenfehlers. Durch die Modernisierung der Herzchirurgie hat sich in den letzten Jahren zunehmend der Trend in Richtung minimal-invasiver Eingriffe gewandelt. Die in den letzten Jahren vorgestellten Methoden unterscheiden sich hauptsächlich im Zugangsweg. Der rechtsseitige anterolaterale Zugang ist aufgrund der guten Sicht auf die Mitralklappe inzwischen sowohl national als auch international als minimal-invasiver Zugang der Wahl etabliert. In wenigen spezialisierten Zentren wird darüber hinaus der videoassistierte total-endoskopische Zugangsweg mit exzellenten Ergebnissen angewendet.
Barriers to Implementing an Artificial Intelligence Model for Unplanned Readmissions
Authors: Baxter Sally L. , Bass Jeremy S. , Sitapati Amy M. 
Published: September 2020

Abstract
Background Electronic health record (EHR) vendors now offer “off-the-shelf” artificial intelligence (AI) models to client organizations. Our health system faced difficulties in promoting end-user utilization of a new AI model for predicting readmissions embedded in the EHR.
Objectives The aim is to conduct a case study centered on identifying barriers to uptake/utilization.
Methods A qualitative study was conducted using interviews with stakeholders. The interviews were used to identify relevant stakeholders, understand current workflows, identify implementation barriers, and formulate future strategies.
Results We discovered substantial variation in existing workflows around readmissions. Some stakeholders did not perform any formal readmissions risk assessment. Others accustomed to using existing risk scores such as LACE+ had concerns about transitioning to a new model. Some stakeholders had existing workflows in place that could accommodate the new model, but they were not previously aware that the new model was in production. Concerns expressed by end-users included: whether the model's predictors were relevant to their work, need for adoption of additional workflow processes, need for training and change management, and potential for unintended consequences (e.g., increased health care resource utilization due to potentially over-referring discharged patients to home health services).
Conclusion AI models for risk stratification, even if “off-the-shelf” by design, are unlikely to be “plug-and-play” in health care settings. Seeking out key stakeholders and defining clear use cases early in the implementation process can better facilitate utilization of these models.
Increased Incidence of Functional Constipation in Children with a History of Perianal Abscess—A Single-Center Retrospective Cohort Study
Authors: Deffaa Oliver Johannes , Gosemann Jan Hendrik , Lacher Martin , Wagner Richard 
Published: September 2020

Abstract
Introduction Functional constipation (FC) is a common gastrointestinal disorder affecting up to 30 % of children. Voluntary stool withholding (e.g., after painful defecation) with consecutive harder and larger stools can result in avoidance patterns. Perianal abscesses (PA) are associated with anal pain and painful stooling. We hypothesized that patients with PA have a higher incidence of subsequent FC compared with children without PA.
Materials and Methods Between January 2010 and December 2016, we retrospectively analyzed all infants (< 365 days of life) presenting at our institution with PA or unilateral inguinal hernia repair (IH; control group). We screened the clinical charts of these patients for outpatient or inpatient visits due to FC according to ROME IV criteria between 01/2010 and 10/2019. Statistical analysis was done using chi-squared test.
Results We included a total of 37 infants with PA and 118 with IH repair (controls). Mean age at presentation for PA was 3.7 ± 0.5 months compared with 4.2 ± 0.3 months at surgery for IH. In the PA group, 6/37 (16%) developed FC compared with 1/118 (1%) in the control group (p-value < 0.01). Patients with PA presented with FC at a mean age of 22.3 ± 4.6 months. Twenty-three of thirty-seven (62%) of PA patients underwent surgery. The development of FC in the PA group was independent of conservative versus surgical treatment (14 vs. 17%, p >0.05).
Conclusion Our study suggests that PA is associated with an increased risk of FC during the further course. Prophylactic stool softening in patients with PA may be considered to prevent subsequent FC.
Phenotypic Switch of Human Peritoneal Macrophages during Childhood
Authors: Schukfeh Nagoud , Elyas Amr , Viemann Dorothee , Ure Benno M. , Froemmel Stephanie , Park Joon-Keun , Kuebler Joachim F. , Vieten Gertrud 
Published: September 2020

Abstract
Introduction Human peritoneal macrophages are resident in the abdominal cavity where they support the specific microenvironmental regulation. We have previously observed a phenotypic switch of murine macrophages during infancy that was associated with a functional development. To investigate the age related changes in human peritoneal macrophages, we analyzed peritoneal macrophages of children undergoing laparoscopic procedures.
Materials and Methods Immunologically healthy children who received minimally invasive surgery in our department were included in this study. In all cases, the written consent was obtained. At the beginning of laparoscopy, physiologic NaCl-solution was instilled and manually removed through the umbilical trocar to gain macrophages. Lavage cells were processed for flow cytometry analysis. CD14+ myeloid cells were monitored for specific lineage marker expression.
Results A total of 21 donors (age: 7 days–18 years) were included and divided into three groups. In all age groups, 97% of myeloid cells expressed CD11b. 70% of these expressed CD14. Three subsets of CD14 cells were detected on the basis of CD14/CD16 expression (CD14 + CD16dim, CD14 + CD16inter, and CD14 + CD16high). In neonates, >80% belonged to the CD14 + CD16high subset, reducing to 30% in adolescents. In none of the cases, the M2 markers CD23 and CD25 were expressed.
Conclusion This is the first study showing that lineage marker expression of peritoneal macrophages in neonates differs from that in adults. The knowledge about neonatal tissue resident macrophages might help to understand their complex interaction and to use specific macrophage properties for therapeutic approaches.