bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway
Authors: Luo Xigang , Sun Dapeng , Wang Yinxiang , Zhang Fengxiang , Wang Yi 
Published: September 2020

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify the effects and the mechanisms of carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was upregulated in a model of liver injury in mice. Thus, overexpression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-px) levels in an in vitro model of liver injury. It was also shown that overexpression of Cpt1a suppressed the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.
Tetrahydroxystilbene glucoside alleviates angiotensin II induced HUVEC senescence via SIRT1
Authors: Fan Wenxue , Guo Yan , Cao Shidong , Cao Shuyu , Xie Yuefeng , Liu Xiangdong , Jin Bo 
Published: September 2020

Tetrahydroxystilbene glucoside (TSG), an active ingredient of Polygonum multiflorum, has been known for certain anti-aging effects. In this study, the possible protective mechanism of TSG on human umbilical vein endothelial cell (HUVEC) senescence induced by angiotensin II (Ang II) was investigated. The results revealed that TSG pretreatment could reduce the percentage of senescence-associated β-galactosidase (SA-β-gal) positive cells and decrease the expression levels of the cellular senescence biomarker proteins p53 and PAI-1. At the same time, the expression of SIRT1 in senescent cells showed an upward trend due to TSG treatment. When inhibiting the expression of SIRT1 by EX527, our results showed that TSG reversed the effect of EX527 by promoting the expression level of SIRT1, reducing the expression of SA-β-gal positive cells and the expression level of p53 and PAI-1 proteins. The present study demonstrated that TSG could protect against HUVEC senescence induced by Ang II, potentially through modulation of SIRT1 activity.
On the connection between quark propagation and hadronization
Authors: Accardi Alberto , Signori Andrea 
Published: September 2020

AbstractWe investigate the properties and structure of the recently discussed “fully inclusive jet correlator”, namely, the gauge-invariant field correlator characterizing the final state hadrons produced by a free quark as this propagates in the vacuum. Working at the operator level, we connect this object to the single-hadron fragmentation correlator of a quark, and exploit a novel gauge invariant spectral decomposition technique to derive a complete set of momentum sum rules for quark fragmentation functions up to twist-3 level; known results are recovered, and new sum rules proposed. We then show how one can explicitly connect quark hadronization and dynamical quark mass generation by studying the inclusive jet’s gauge-invariant mass term. This mass is, on the one hand, theoretically related to the integrated chiral-odd spectral function of the quark, and, on the other hand, is experimentally accessible through the E and $${\widetilde{E}}$$

E
~

twist-3 fragmentation function sum rules. Thus, measurements of these fragmentation functions in deep inelastic processes provide one with an experimental gateway into the dynamical generation of mass in Quantum Chromodynamics.
YAP and AP-1 Cooperate to Initiate Pancreatic Cancer Development from Ductal Cells in Mice
Authors: Park Jaeoh , Eisenbarth David , Choi Wonyoung , Kim Hail , Choi Chan , Lee Dahye , Lim Dae-Sik 
Published: September 2020

Abstract

The development of pancreatic cancer is heavily dependent upon the aberrant activation of KRAS signaling. Among the downstream targets of KRAS, the effectors of the Hippo pathway YAP and TAZ (YAP/TAZ) are crucial during cancer initiation and progression. However, little is known about the cell type-specific effects of YAP/TAZ on the development of pancreatic cancer. Here we clarify the unique consequences of YAP/TAZ activation in the ductal cell population of the pancreas by generating mice with pancreatic duct cell-specific, inducible knockouts of Lats1 and Lats2, the main kinases upstream of YAP/TAZ. Oncogenic activation of YAP by deletion of Lats1/2 in ductal cells led to the rapid transformation of the pancreas, which was accompanied by a robust increase in the expression of YAP and AP-1 target genes. Pharmacologic inhibition of AP-1 activity induced death in Lats1/2 knockout organoids and attenuated YAP-dependent transformation of the pancreas in vivo. Both YAP and AP-1 were activated during the development of KRAS-dependent cancer in mice and human patients with pancreatic ductal adenocarcinoma, suggesting that this signaling hub represents an important mediator of pancreatic cancer development and progression. Collectively, these data define a YAP-dependent mechanism of pancreatic cancer cell development and suggest that inhibition of AP-1 can suppress this development.

Significance:
A pancreatic ductal cell-specific knockout mouse model featuring constitutively active YAP allows for the study of YAP-dependent transformation of the pancreas and for screening pharmacologically active inhibitors.
AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models
Authors: Ferreira Sofia , Foray Chloe , Gatto Alberto , Larcher Magalie , Heinrich Sophie , Lupu Mihaela , Mispelter Joel , Boussin François D. , Pouponnot Célio , Dutreix Marie 
Published: September 2020

Abstract

Purpose:
Medulloblastoma is an important cause of mortality and morbidity in pediatric oncology. Here, we investigated whether the DNA repair inhibitor, AsiDNA, could help address a significant unmet clinical need in medulloblastoma care, by improving radiotherapy efficacy without increasing radiation-associated toxicity.

Experimental Design:
To evaluate the brain permeability of AsiDNA upon systemic delivery, we intraperitoneally injected a fluorescence form of AsiDNA in models harboring brain tumors and in models still in development. Studies evaluated toxicity associated with combination of AsiDNA with radiation in the treatment of young developing animals at subacute levels, related to growth and development, and at chronic levels, related to brain organization and cognitive skills. Efficacy of the combination of AsiDNA with radiation was tested in two different preclinical xenografted models of high-risk medulloblastoma and in a panel of medulloblastoma cell lines from different molecular subgroups and TP53 status. Role of TP53 on the AsiDNA-mediated radiosensitization was analyzed by RNA-sequencing, DNA repair recruitment, and cell death assays.

Results:
Capable of penetrating young brain tissues, AsiDNA showed no added toxicity to radiation. Combination of AsiDNA with radiotherapy improved the survival of animal models more efficiently than increasing radiation doses. Medulloblastoma radiosensitization by AsiDNA was not restricted to a specific molecular group or status of TP53. Molecular mechanisms of AsiDNA, previously observed in adult malignancies, were conserved in pediatric models and resembled dose increase when combined with irradiation.

Conclusions:
Our results suggest that AsiDNA is an attractive candidate to improve radiotherapy in medulloblastoma, with no indication of additional toxicity in developing brain tissues.
Unique Transcriptome Signature Distinguishes Patients With Heart Failure With Myopathy
Authors: Caspi Talia , Straw Sam , Cheng Chew , Garnham Jack O , Scragg Jason L. , Smith Jessica , Koshy Aaron O. , Levelt Eylem , Sukumar Piruthivi , Gierula John , Beech David J. , Kearney Mark T. , Cubbon Richard M. , Wheatcroft Stephen B. , Witte Klaus K. , Roberts Lee D. , Bowen T. Scott 
Published: September 2020

Background
People with chronic heart failure (CHF) experience severe skeletal muscle dysfunction, characterized by mitochondrial abnormalities, which exacerbates the primary symptom of exercise intolerance. However, the molecular triggers and characteristics underlying mitochondrial abnormalities caused by CHF remain poorly understood.

Methods and Results
We recruited 28 patients with CHF caused by reduced ejection fraction and 9 controls. We simultaneously biopsied skeletal muscle from the pectoralis major in the upper limb and from the vastus lateralis in the lower limb. We phenotyped mitochondrial function in permeabilized myofibers from both sites and followed this by complete RNA sequencing to identify novel molecular abnormalities in CHF skeletal muscle. Patients with CHF presented with upper and lower limb skeletal muscle impairments to mitochondrial function that were of a similar deficit and indicative of a myopathy. Mitochondrial abnormalities were strongly correlated to symptoms. Further RNA sequencing revealed a unique transcriptome signature in CHF skeletal muscle characterized by a novel triad of differentially expressed genes related to deficits in energy metabolism including adenosine monophosphate deaminase 3, pyridine nucleotide‐disulphide oxidoreductase domain 2, and lactate dehydrogenase C.

Conclusions
Our data suggest an upper and lower limb metabolic myopathy that is characterized by a unique transcriptome signature in skeletal muscle of humans with CHF.
Evidence‐Based Medicine in Otolaryngology Part XII: Assessing Patient Preferences
Authors: Naunheim Matthew R. , Randolph Gregory W. , Shin Jennifer J. 
Published: September 2020

ObjectiveTo provide a contemporary resource to update clinicians and researchers on the current state of assessment of patient preferences.Data SourcesPublished studies and literature regarding patient preferences, evidence‐based practice, and patient‐centered management in otolaryngology.Review MethodsPatients make choices based on both physician input and their own preferences. These preferences are informed by personal values and attitudes, and they ideally result from a deliberative evaluation of the risks, benefits, and other outcomes pertaining to medical care. To date, rigorous evaluation of patient preferences for otolaryngologic conditions has not been integrated into clinical practice or research. This installment of the “Evidence‐Based Medicine in Otolaryngology” series focuses on formal assessment of patient preferences and the optimal methods to determine them.ConclusionsMethods have been developed to optimize our understanding of patient preferences.Implications for PracticeUnderstanding these patient preferences may help promote an evidence‐based approach to the care of individual patients.
Communicating Oncologic Prognosis With Empathy: A Pilot Study of a Novel Communication Guide
Authors: Lippe Megan , Farya Phillips , Jennifer McCulloch , Stanley Alexandra , Barbara Jones , Boone Goodgame 
Published: September 2020

Background: Clear communication between patients, families, and health-care providers is imperative to maximize patient outcomes, particularly for patients diagnosed with incurable cancer who require prompt engagement in decision-making. In response to the need to engage in quality patient-centered communication, an interprofessional team, representing medicine, nursing, social work, spiritual care, and clinical psychology, explored extant literature and developed a simple, single-page communication guide that summarizes the prognosis for patients with incurable cancers. The tool was specifically designed to enhance communication for patients, families, and across all members of the treatment and patient support team. Purpose: The purpose of this pilot study was to evaluate the impact of the communication guide on patient’s accurate understanding of prognosis and the feasibility and acceptability of the intervention. Methods: The study employed a sequential explanatory mixed-method design. Using pre- and post-tests, participants completed a prognosis and treatment perception survey and were randomized into control or intervention groups based on preference for prognostic information. The oncologist utilized the communication guide with the participants in the intervention group. Finally, 6-week post-test surveys were completed, followed by an exit interview. Results: Key findings revealed participants prefer receiving detailed information about prognosis and have differing perceptions compared to the oncologists. Understandings of prognosis for patients and oncologists became more congruent following use of the communication guide. Participants found the tool useful and helpful. Conclusions: The communication tool serves as a promising mechanism to enhance patient-centered communication about prognosis for patients with incurable cancer.
Fluid therapy in mechanically ventilated critically ill children: the sodium, chloride and water burden of fluid creep
Authors: Langer Thomas , D’Oria Veronica , Spolidoro Giulia C. I. , Chidini Giovanna , Scalia Catenacci Stefano , Marchesi Tiziana , Guerrini Marta , Cislaghi Andrea , Agostoni Carlo , Pesenti Antonio , Calderini Edoardo 
Published: September 2020

Abstract
Background
Fluid therapy is a cornerstone of pediatric intensive care medicine. We aimed at quantifying the load of water, sodium and chloride due to different fluid indications in our pediatric intensive care unit (PICU). We were particularly interested in the role of fluid creep, i.e. fluid administered mainly as the vehicle for drugs, and the association between sodium load and water balance.

Methods
Critically ill children aged ≤3 years and invasively ventilated for ≥48 h between 2016 and 2019 in a single tertiary center PICU were retrospectively enrolled. Need for renal replacement therapy, plasmapheresis or parenteral nutrition constituted exclusion criteria. Quantity, quality and indication of fluids administered intravenously or enterally, urinary output and fluid balance were recorded for the first 48 h following intubation. Concentrations of sodium and chloride provided by the manufacturers were used to compute the electrolyte load.

Results
Forty-three patients (median 7 months (IQR 3–15)) were enrolled. Patients received 1004 ± 284 ml of water daily (153 ± 36 ml/kg/day), mainly due to enteral (39%), creep (34%) and maintenance (24%) fluids. Patients received 14.4 ± 4.8 mEq/kg/day of sodium and 13.6 ± 4.7 mEq/kg/day of chloride, respectively. The majority of sodium and chloride derived from fluid creep (56 and 58%). Daily fluid balance was 417 ± 221 ml (64 ± 30 ml/kg/day) and was associated with total sodium intake (r2 = 0.49, p < 0.001).

Conclusions
Critically ill children are exposed, especially in the acute phase, to extremely high loads of water, sodium and chloride, possibly contributing to edema development. Fluid creep is quantitatively the most relevant fluid in the PICU and future research efforts should address this topic in order to reduce the inadvertent water and electrolyte burden and improve the quality of care of critically ill children.
An exploration of the experiences of GP registrar supervisors in small rural communities: a qualitative study
Authors: Couch Danielle , O’Sullivan Belinda , Russell Deborah , McGrail Matthew , Wallace Glen , Bentley Michael 
Published: September 2020

Abstract
Background
In Australia registrar training to become a general practitioner (GP) involves three to four years of supervised learning with at least 50% of GP registrars training wholly in rural areas. In particular rural over regional GP placements are important for developing future GPs with broader skills because the rural scope of practice is wider. Having enough GP supervisors in smaller rural communities is essential such training. We aimed to explore what makes rural GPs’ based outside of major regional centres, participate in supervising or not, their experiences of supervising, and impact of their practice context.

Methods
Semi-structured interviews were undertaken with 25 GPs based in rural Tasmania (outside of major regions - Hobart and Launceston), in towns of < 25,000 population, to explore the GPs’ professional backgrounds, their experiences of supervising GP registrars, their practice context and their decisions about supervising GP registrars or not. Thematic analysis was undertaken; key ideas, concepts and experiences were identified and then reviewed and further refined to core themes.

Results
Supervising was perceived to positively impact on quality of clinical care, reduce busy-ness and improve patient access to primary care. It was energising for GPs working in rural contexts. Rural GPs noted business factors impacted the decision to participate in supervision and the experience of participating: including uncertainty and discontinuity of registrar supply (rotational training systems), registrar competence and generating income.

Conclusions
Supervising is strongly positive for rural GPs and related to job satisfaction but increasing supervision capacity in rural areas may depend on better policies to assure continuity of rural registrars as well as policies and systems that enable viable supervision models tailored to the context.
Macrophage accumulation within coronary arterial wall in diabetic patients with acute coronary syndrome: a study with in-vivo intravascular imaging modalities
Authors: Kogo Takaaki , Hiro Takafumi , Kitano Daisuke , Takayama Tadateru , Fukamachi Daisuke , Morikawa Tomoyuki , Sudo Mitsumasa , Okumura Yasuo 
Published: September 2020

Abstract
Background and aims
Macrophage accumulation in arteriosclerotic plaque of coronary arteries is involved in plaque destabilization. Atherosclerosis has been known to be progressive in patients with type 2 diabetes mellitus (DM). This study compared the features of 3-dimensional (3D) spatial distribution of macrophage accumulation within coronary artery wall between acute coronary syndrome (ACS) patients with DM (n = 20) and those without (non-DM, n = 20) by using intravascular ultrasound (IVUS) and optical coherence tomography (OCT).

Methods
The OCT-derived macrophage accumulation was measured within the proximal left anterior-descending artery. This measurement was performed for the whole vessel segment of interest, higher shear stress region (flow divider side) and lower shear stress region (the opposite side).

Results
Normalized macrophage accumulation per unit length of the whole segment of interest was significantly larger in ACS patients with DM than without. In non-DM patients, macrophage density per IVUS-derived plaque volume was significantly higher in high shear stress region compared to low shear stress region, however, there was no significant difference between the two regions in DM patients. The macrophage density in the low shear stress region was significantly higher in the DM group than in the non-DM group. A multivariate analysis showed that the presence of DM was a major determinant for macrophage distribution.

Conclusions
Macrophage accumulation was more abundant and homogeneous within coronary arterial wall in DM patients with ACS compared to non-DM patients, suggesting that plaque destabilization may occur more widely throughout coronary wall in DM patients.
Establishment and characterization of a new gastric cancer cell line, XGC-1
Authors: Peng Jigui , Xu Hao , Cai Jianchun 
Published: September 2020

Abstract
Background
To establish a primary human gastric cancer cell line.

Methods
Fresh gastric cancer tissue samples were separated into a cell suspension, and DMEM/F12 medium containing 10% foetal bovine serum was used for primary culture and subculture. The morphology of the cells was observed under a light microscope, and the cell growth curve was plotted. A soft agar colony formation assay was used to detect the colony formation ability of the cell line. Immunohistochemical methods were used to detect cytokeratin, vimentin and Ki-67, the chromosome G banding method was used to analyse the karyotype of the cells, and the tumourigenic ability of the cells was detected by subcutaneous inoculation of BALB/C nude mice.

Results
We established a gastric cancer cell line from a 68-year-old male patient. This gastric cancer cell line was named XGC-1 and had a doubling time of approximately 48 h. The cell line displayed strong colony formation ability and tumourigenicity in BALB/C nude mice and had complicated chromosomal abnormalities. When nutrients were insufficient, the cells shed and floated in the medium, but adherent growth was observed in nutrient-rich conditions.

Conclusions
The XGC-1 cell line will be useful for future studies of gastric cancer development, progression, metastasis and therapy.
Pathways leading to prevention of fatal and non-fatal cardiovascular disease: An interaction model on 15 years population-based cohort study
Authors: Shakibaei Najmeh , Hassannejad Razieh , Mohammadifard Noushin , Marateb Hamid Reza , Mansourian Marjan , Mañanas Miguel Angel , Sarrafzadegan Nizal 
Published: September 2020

Abstract
Background
A comprehensive study on the interaction of cardiovascular disease (CVD) risk factors is critical to prevent cardiovascular events. The main focus of this study is thus to understand direct and indirect relationships between different CVD risk factors.

Methods
A longitudinal data on adults aged ≥35 years, who were free of CVD at baseline, were used in this study. The endpoints were CVD events, whereas their measurements were demographic, lifestyle components, socio-economics, anthropometric measures, laboratory findings, quality of life status, and psychological factors. A Bayesian structural equation modelling was used to determine the relationships among 21 relevant factors associated with total CVD, stroke, acute coronary syndrome (ACS), and fatal CVDs.

Results
In this study, a total of 3161 individuals with complete information were involved in the study. A total of 407 CVD events, with an average age of 54.77(10.66) years, occurred during follow-up. The causal associations between six latent variables were identified in the causal network for fatal and non-fatal CVDs. Lipid profile, with the coefficient of 0.26 (0.01), influenced the occurrence of CVD events as the most critical factor, while it was indirectly mediated through risky behaviours and comorbidities. Lipid profile at baseline was influenced by a wide range of other protective factors, such as quality of life and healthy lifestyle components.

Conclusions
Analysing a causal network of risk factors revealed the flow of information in direct and indirect paths. It also determined predictors and demonstrated the utility of integrating multi-factor data in a complex framework to identify novel preventable pathways to reduce the risk of CVDs.