bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway
Authors: Zhao Shuhua , Cheng Lu , Shi Yuan , Li Jia , Yun Qinghui , Yang Hong 
Published: January 2021

AbstractMIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has no significant effect on fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo fatty acid synthesis through up-regulating the expression of sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted cholesterol biosynthesis through up-regulating the expression of sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and metastasis assays indicated that MIEF2-regulated fatty acid synthesis and cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this malignancy.
TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy
Authors: Zhang Huan-Tian , Zeng Qingzhong , Wu Baomeng , Lu Junlei , Tong Kui-Leung , Lin Jiebin , Liu Qiu-Yu , Xu Lipei , Yang Jie , Liu Xiaohui , Liu Wanting , Zhang Yun-Fang , Lian Qionghua , Liu Langxia , Gao Xuejuan 
Published: January 2021

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown. In the present study, we first showed that TRIM21 could promote OS cell autophagy, as determined by the accumulation of LC3-II, and the degradation of cargo receptor p62. Further, we were able to identify that Annexin A2 (ANXA2), as a novel interacting partner of TRIM21, was critical for TIRM21-induced OS cell autophagy. Although TRIM21 had a negligible effect on the mRNA and protein expressions of ANXA2, we did find that TRIM21 facilitated the translocation of ANXA2 toward plasma membrane (PM) in OS cells through a manner relying on TRIM21-mediated cell autophagy. This functional link has been confirmed by observing a nice co-expression of TRIM21 and ANXA2 (at the PM) in the OS tissues. Mechanistically, we demonstrated that TRIM21, via facilitating the ANXA2 trafficking at the PM, enabled to release the transcription factor EB (TFEB, a master regulator of autophagy) from the ANXA2-TFEB complex, which in turn entered into the nucleus for the regulation of OS cell autophagy. In accord with previous findings that autophagy plays a critical role in the control of differentiation, we also demonstrated that autophagy inhibited OS cell differentiation, and that the TRIM21/ANXA2/TFEB axis is implicated in OS cell differentiation through the coordination with autophagy. Taken together, our results suggest that the TRIM21/ANXA2/TFEB axis is involved in OS cell autophagy and subsequent differentiation, indicating that targeting this signaling axis might lead to a new clue for OS treatment.
NF-κB activity during pancreas development regulates adult β-cell mass by modulating neonatal β-cell proliferation and apoptosis
Authors: Sever Dror , Hershko-Moshe Anat , Srivastava Rohit , Eldor Roy , Hibsher Daniel , Keren-Shaul Hadas , Amit Ido , Bertuzzi Federico , Krogvold Lars , Dahl-Jørgensen Knut , Ben-Dov Iddo Z. , Landsman Limor , Melloul Danielle 
Published: January 2021

AbstractNF-κB is a well-characterized transcription factor, widely known for its roles in inflammation and immune responses, as well as in control of cell division and apoptosis. However, its function in β-cells is still being debated, as it appears to depend on the timing and kinetics of its activation. To elucidate the temporal role of NF-κB in vivo, we have generated two transgenic mouse models, the ToIβ and NOD/ToIβ mice, in which NF-κB activation is specifically and conditionally inhibited in β-cells. In this study, we present a novel function of the canonical NF-κB pathway during murine islet β-cell development. Interestingly, inhibiting the NF-κB pathway in β-cells during embryogenesis, but not after birth, in both ToIβ and NOD/ToIβ mice, increased β-cell turnover, ultimately resulting in a reduced β-cell mass. On the NOD background, this was associated with a marked increase in insulitis and diabetes incidence. While a robust nuclear immunoreactivity of the NF-κB p65-subunit was found in neonatal β-cells, significant activation was not detected in β-cells of either adult NOD/ToIβ mice or in the pancreata of recently diagnosed adult T1D patients. Moreover, in NOD/ToIβ mice, inhibiting NF-κB post-weaning had no effect on the development of diabetes or β-cell dysfunction. In conclusion, our data point to NF-κB as an important component of the physiological regulatory circuit that controls the balance of β-cell proliferation and apoptosis in the early developmental stages of insulin-producing cells, thus modulating β-cell mass and the development of diabetes in the mouse model of T1D.
Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance
Authors: Ting Darren Shu Jeng , Ho Charlotte Shan , Deshmukh Rashmi , Said Dalia G. , Dua Harminder S. 
Published: January 2021

AbstractCorneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5–2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral andAcanthamoebakeratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.
Impact of macular fluid volume fluctuations on visual acuity during anti-VEGF therapy in eyes with nAMD
Authors: Chakravarthy Usha , Havilio Moshe , Syntosi Annie , Pillai Natasha , Wilkes Emily , Benyamini Gidi , Best Catherine , Sagkriotis Alexandros 
Published: January 2021

Abstract
Objectives
To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD).

Methods
Data were extracted from electronic medical records of 381 nAMD patients, aged ≥50 years; baseline VA ≥33 and ≤73 letters; ≥24 months’ follow-up and ≥2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression.

Results
By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: −12.9 to −6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0–0.7] versus 0.8 [0.5–1.0]; SRF: 0.0 [0.0–0.5] versus 0.6 [0.3–1.0]).

Conclusions
Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.
TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii
Authors: Khelifa Asma S. , Guillen Sanchez Cecilia , Lesage Kevin M. , Huot Ludovic , Mouveaux Thomas , Pericard Pierre , Barois Nicolas , Touzet Helene , Marot Guillemette , Roger Emmanuel , Gissot Mathieu 
Published: January 2021

AbstractApicomplexan parasites have evolved efficient and distinctive strategies for intracellular replication where the timing of emergence of the daughter cells (budding) is a decisive element. However, the molecular mechanisms that provide the proper timing of parasite budding remain unknown. Using Toxoplasma gondii as a model Apicomplexan, we identified a master regulator that controls the timing of the budding process. We show that an ApiAP2 transcription factor, TgAP2IX-5, controls cell cycle events downstream of centrosome duplication. TgAP2IX-5 binds to the promoter of hundreds of genes and controls the activation of the budding-specific cell cycle expression program. TgAP2IX-5 regulates the expression of specific transcription factors that are necessary for the completion of the budding cycle. Moreover, TgAP2IX-5 acts as a limiting factor that ensures that asexual proliferation continues by promoting the inhibition of the differentiation pathway. Therefore, TgAP2IX-5 is a master regulator that controls both cell cycle and developmental pathways.
Overcoming the barriers to dissemination and implementation of quality measures for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) position statement
Authors: Bisschops Raf , Rutter Matthew D. , Areia Miguel , Spada Cristiano , Domagk Dirk , Kaminski Michel F. , Veitch Andrew , Khannoussi Wafaa , Gralnek Ian M. , Hassan Cesare , Messmann Helmut , Ponchon Thierry , Fockens Paul , Dignass Alex , Dinis-Ribeiro Mario 
Published: January 2021

AbstractThe European Society of Gastrointestinal Endoscopy (ESGE) has developed performance measures and established a framework for quality assessment for gastrointestinal endoscopy in Europe. Most national societies actively undertake initiatives to implement and explicitly endorse these quality indicators. Given this, ESGE proposes that, at a national level, strong leadership should exist to disseminate and implement quality parameters. Thus, understanding the potential barriers that may vary locally is of paramount importance. ESGE suggests that each national society should prioritize quality and standards of care in gastrointestinal endoscopy in their activities and should survey/understand which measures are a local priority to their members and make measuring quality intrinsic to daily endoscopy practice.
Nutzungsgrad und Nutzergruppen der Online-Videosprechstunde in der
ambulanten ärztlichen Versorgung – Eine
Routinedatenanalyse
Authors: Gensorowsky Daniel , Surmann Bastian , Schmidt Juliana , Greiner Wolfgang 
Published: January 2021

Zusammenfassung
Ziel Trotz wahrgenommener Potenziale, einer Abrechenbarkeit als
Regelleistung gegenüber der gesetzlichen Krankenversicherung und
verschiedener Fördermaßnahmen hat sich die
Online-Videosprechstunde noch nicht als fester Bestandteil des ambulanten
Versorgungsalltags etabliert. An längerfristigen quantitativen
Untersuchungen zum Nutzungsgrad mangelt es bislang. Diese sind jedoch
essenziell für ein besseres Verständnis der
Diffusionsprozesse sowie der Auswirkungen von
Fördermaßnahmen. Die vorliegende Arbeit stellt einen ersten
Schritt in Richtung einer fortlaufenden Begleitforschung dar.
Methodik Die Entwicklung des Nutzungsgrades der Videosprechstunde in
der ambulant ärztlichen Versorgung wird auf Grundlage von
Routineabrechnungsdaten einer großen gesetzlichen Krankenkasse von
Beginn der Erstattungsfähigkeit im April 2017 bis Ende 2018
untersucht. Um einen Überblick über die Nutzergruppen zu
erhalten, werden zudem relevante und in den Abrechnungsdaten abbildbare
Arzt- und Patientencharakteristika (Facharztgruppe, Alter, Region)
untersucht.
Ergebnisse In den 21 Monaten des Beobachtungszeitraumes wurden
insgesamt 320 Videosprechstunden abgerechnet, wobei die Nutzungszahlen in
2018 monatlich bereits doppelt so hoch waren, wie in 2017. Insgesamt nahmen
105 verschiedene Versicherte eine Videosprechstunde in Anspruch. Diese
hatten ein Durchschnittsalter von 74,6 Jahren und kamen mit 59,8%
vorwiegend aus städtischen Regionen. Unter den insgesamt 30
Ärzten, die Videosprechstunden durchgeführt haben, stellten
die Allgemeinmediziner mit 36,7% die größte
Facharztgruppe.
Schlussfolgerung Die Untersuchung unterstreicht den geringen
Stellenwert der Online-Videosprechstunde in der ambulanten
ärztlichen Versorgung in den ersten 21 Monaten nach ihrer
Einführung. Die Ergebnisse decken sich mit den bisherigen
Erkenntnissen aus Kurzfristanalysen und demoskopischen Untersuchungen. Sie
deuten darüber hinaus auf erste Nutzungstrends hin, die es im Rahmen
einer kontinuierlichen Auseinandersetzung weiter zu untersuchen gilt. Eine
entsprechende Begleitforschung sollte den Beobachtungszeitraum fortlaufend
ausweiten und eine breitere, kassenübergreifende Datenbasis
anstreben.
Sequencing Groebke–Blackburn–Bienaymé and Aza-Michael Addition Reactions: A Modular Strategy for Accessing a Diverse Collection of Constrained Benzoxazepine and Imidazopyrazine Systems
Authors: Al-Tel Taleb H. , Srinivasulu Vunnam , Al-Marzooq Farah , Hamad Mohamad , Khanfar Monther A. , Ramanathan Mani , Soares Nelson C. 
Published: January 2021

AbstractWe present a divergent strategy that permits access to diversely functionalized benzoxazepinium scaffolds fused to various heterocycles. The described strategy features a one-pot combination of the Groebke–Blackburn–Bienaymé reaction and an aza-Michael addition. Methyl (E)-4-(2-formylphenoxy)but-2-enoate and its derivatives are utilized as central elements in this cascade. These building blocks are reacted with a variety of functionalized amino-azines and tert-butyl isocyanide under ytterbium triflate [Yb(OTf)3] catalysis. The ensuing cascade represents a rapid, modular and atom-economic process that leads to the construction of a diverse collection of constrained benzoxazepinium systems from a wide substrate scope.
Insights from In Vitro and Clinical Data to Guide Transition from the Novel P2Y12 Antagonist Selatogrel to Clopidogrel, Prasugrel, and Ticagrelor
Authors: Schilling Uta , Dingemanse Jasper , Dobrow Michael , Baumann Martine , Riederer Markus A. , Juif Pierre-Eric , Ufer Mike 
Published: January 2021

AbstractReduced pharmacodynamic (PD) effects of irreversible oral P2Y12 receptor antagonists have been reported when administered during cangrelor infusion. Therefore, the PD interaction liability of the novel P2Y12 receptor antagonist selatogrel with irreversible (i.e., clopidogrel, prasugrel) and reversible (i.e., ticagrelor) oral P2Y12 receptor antagonists was investigated in vitro and in healthy subjects. In vitro, selatogrel reduced the effects of clopidogrel and prasugrel in a concentration-dependent manner, while additive effects were observed for the combination of selatogrel and ticagrelor. Accordingly, a single-center, randomized, double-blind, two-way crossover study was conducted consisting of six groups. In each group (N = 12), an open-label loading dose of 300 or 600 mg clopidogrel, 60 mg prasugrel, or 180 mg ticagrelor was administered 30 minutes (i.e., at t
max of selatogrel) or 12 hours after a single subcutaneous dose of 16 mg selatogrel or placebo. Inhibition of platelet aggregation (IPA) was assessed at various time points up to 48 hours. Reduced IPA was determined when clopidogrel or prasugrel was administered 30 minutes after selatogrel (∼40 and 70% lower IPA, respectively, at 24 hours postdosing). However, when administering prasugrel 12 hours after selatogrel, IPA was not impacted (>90% IPA) and in the case of clopidogrel reduced effects were partially mitigated. Similar IPA was determined for ticagrelor when administered 30 minutes after selatogrel or placebo. In conclusion, reduced IPA was observed for clopidogrel and prasugrel when administered after selatogrel, which can be mitigated by applying an appropriate time interval. No PD interaction with ticagrelor was observed.
Mapping the intermedia agenda setting (IAS) literature
Authors: Su Yan , Xiao Xizhu 
Published: January 2021

Abstract
This study systematically reviewed empirical intermedia agenda setting (IAS) research published between 1997 and 2019, in terms of the level of agenda-setting, the methodologies – including the coding strategies and time-series analytical techniques – the types of media, and the flow of IAS effects. According to our results, previous IAS studies exhibited the following trends: (1) an overwhelming majority of the IAS studies was anchored by the first agenda-setting level, whilst examinations of the NAS model and multiple levels have increased in recent years; (2) excessive IAS studies performed content analyses, (3) applied manual coding strategies, (4) conducted cross-lagged correlation analyses to examine time-series effects, (5) and focused on newspapers and Twitter; (6) most IAS research confirmed the flow from one traditional media to another traditional media, whereas more recent studies also revealed the flow from traditional to emerging media, and their reciprocal relationship; (7) the majority of IAS studies confirmed the elite-to-non-elite flow of IAS effects. Based on these findings, this study encourages futures IAS researchers to attach more importance to (1) contextual diversity, (2) balanced examinations of each agenda-setting level, (3) methodological innovations, (4) technological pluralism, and (5) providing more evidence for the flow of IAS effects across different types of media.
Invited Commentary: Medicaid Policy and Pregnancy Outcomes—Toward a Reproductive Autonomy Framework
Authors: Jarlenski Marian 
Published: January 2021

AbstractThe Medicaid program covers more than 70 million people and is the largest single health insurance payer for pregnancy and delivery in the United States. In this issue of the Journal, Margerison et al. (Am J Epidemiol. 2021;190(8):1488–1498) investigate the extent to which expansion of Medicaid coverage to nonpregnant low-income adults under the Affordable Care Act may have improved prepregnancy or birth outcomes. They found that Medicaid expansions by states were not associated with changes in prepregnancy health, including smoking and obesity. Similarly, there were no changes in preterm birth or small or large size for gestational age attributable to Medicaid expansion. Results were consistent across a range of model specifications and with allowance for different lag times between Medicaid expansion and pregnancy. The results are consistent with prior research finding that pregnancy-specific Medicaid expansions did not uniformly translate to improved pregnancy and birth outcomes. Results should be interpreted in light of the limited contribution that medical services make to overall health and well-being. To reduce the high rates of adverse pregnancy and child health outcomes in the United States, Medicaid policy must move toward a reproductive autonomy framework that shifts the focus away from pregnancy-specific benefits and toward a comprehensive and patient-empowering reproductive health paradigm.
The Role of Mitochondrial Dysfunction in Preeclampsia: Causative Factor or Collateral Damage?
Authors: Smith Alex N , Wang Xi , Thomas Daniel G , Tatum Robert E , Booz George W , Cunningham Mark W 
Published: January 2021

AbstractPreeclampsia, new onset hypertension in pregnancy, affects ~5%–10% of the world’s population. Preeclampsia is the leading cause of morbidity and mortality for both the mother and fetus. As of today, there is no cure for this disease except for delivery of the fetal–placental unit. The exact causation and onset of the disease are unknown. However, recent studies have shown a strong correlation between mitochondrial dysfunction and preeclampsia. Circulating mitochondrial DNA, elevated reactive oxygen species, angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA), activated natural killer cells, and upregulated inflammatory responses all contribute to mitochondrial dysfunction and the pathophysiology of preeclampsia. This review summarizes the current literature of both experimental and clinical observations that support the hypothesis that mitochondrial dysfunction contributes to the pathophysiology of preeclampsia and may be a precursor to the disease onset. This review will also address the use of therapies to improve mitochondrial dysfunction in preeclampsia.