bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial
GNAQ
p.R183Q Increases ANGPT2 (Angiopoietin-2) and Drives Formation of Enlarged Blood Vessels
Authors: Huang Lan , Bichsel Colette , Norris Alexis L. , Thorpe Jeremy , Pevsner Jonathan , Alexandrescu Sanda , Pinto Anna , Zurakowski David , Kleiman Robin J. , Sahin Mustafa , Greene Arin K. , Bischoff Joyce 
Published: October 2021

Objective:

Capillary malformation (CM) occurs sporadically and is associated with Sturge-Weber syndrome. The somatic mosaic mutation in
GNAQ
(c.548G>A, p.R183Q) is enriched in endothelial cells (ECs) in skin CM and Sturge-Weber syndrome brain CM. Our goal was to investigate how the mutant Gαq (G-protein αq subunit) alters EC signaling and disrupts capillary morphogenesis.

Approach and Results:

We used lentiviral constructs to express p.R183Q or wild-type
GNAQ
in normal human endothelial colony forming cells (EC-R183Q and EC-WT, respectively). EC-R183Q constitutively activated PLC (phospholipase C) β3, a downstream effector of Gαq. Activated PLCβ3 was also detected in human CM tissue sections. Bulk RNA sequencing analyses of mutant versus wild-type EC indicated constitutive activation of PKC (protein kinase C), NF-κB (nuclear factor kappa B) and calcineurin signaling in EC-R183Q. Increased expression of downstream targets in these pathways, ANGPT2 (angiopoietin-2) and DSCR (Down syndrome critical region protein) 1.4 were confirmed by quantitative PCR and immunostaining of human CM tissue sections. The Gαq inhibitor YM-254890 as well as siRNA targeted to PLCβ3 reduced mRNA expression levels of these targets in EC-R183Q while the pan-PKC inhibitor AEB071 reduced ANGPT2 but not DSCR1.4. EC-R183Q formed enlarged blood vessels in mice, reminiscent of those found in human CM. shRNA knockdown of ANGPT2 in EC-R183Q normalized the enlarged vessels to sizes comparable those formed by EC-WT.

Conclusions:
Gαq-R183Q, when expressed in ECs, establishes constitutively active PLCβ3 signaling that leads to increased ANGPT2 and a proangiogenic, proinflammatory phenotype. EC-R183Q are sufficient to form enlarged CM-like vessels in mice, and suppression of ANGPT2 prevents the enlargement. Our study provides the first evidence that endothelial Gαq-R183Q is causative for CM and identifies ANGPT2 as a contributor to CM vascular phenotype.
On Stepping Stones and Other Calamities of Marxist Historiography
Authors: Gerstenberger Heide 
Published: October 2021

Abstract
Historical research is always in danger of being made use of for explaining and illustrating instead of testing one’s theoretical conceptions. Since Marxist historical research has certainly not been exempt from this temptation, one has to start any debate about Marxist historiography with the demand to accord empirical research the chance to shake even the cornerstones of one’s own theoretical conceptions. In a paper that has triggered off a new discussion on ‘Political Marxism’, Samuel Knafo and Benno Teschke insist on such a practice. In what follows I try to position the ongoing discussion in the wider context of theoretical concepts of Marxist historiography.
The Networked Diplomacy of Informal International Institutions
Authors: Manulak Michael W. 
Published: October 2021

Abstract
The rise of informal international institutions has been one of the most significant developments in institutional design and choice since the 1990s. While states have increasingly opted for informal governance, little is known about the character of intergovernmental relations in these settings. Scholars, for instance, debate whether great powers dominate such institutions, or whether influence can be exercised by a wider array of players. Drawing from the author’s experience as a government representative within the Proliferation Security Initiative, a leading informal institution, this article provides a theory-driven analysis of intergovernmental interactions within such bodies. It demonstrates that diplomacy within informal institutions tends to assume a decentralized, networked quality that favors actors positioned at the center of intergovernmental networks. In doing so, the article highlights clear means through which central network positions confer influence. The article also sheds new light on the Proliferation Security Initiative and on counterproliferation cooperation more generally.
Ripe for Resolution
Authors: Hinz Kristina , Herz Monica , Siman Maira 
Published: October 2021

Abstract
This article discusses how the institutionalization of international mediation practices and its growing relevance since the end of the Cold War coincided with the formation of an epistemic community that shares common practices for a third party. This community focuses on core concepts that structure mediation practices such as efficiency, rationality, and the management of time and information. The article analyzes the consolidation of this community through the circulation of knowledge among scholars and practitioners. In particular, it highlights the place of the concept of ripeness, developed by Ira William Zartman, in stabilizing a division between a moment of conflict and a moment of nonconflict; and it discusses the place of the UN system in its dissemination among mediation practitioners. The article argues that the project-oriented understanding of mediation practices that arises from these shared conceptions contributes to an insulation of these practices from broader views of conflict within international politics.
Political implications of compassion in Mencius
Authors: Arunkhajornsak Sarinya 
Published: October 2021

AbstractThis paper examines Mencius’ view on compassion in the political realm by proposing that Mencius defends compassionate governance by reconciling the two extremes of Yangist self-love and Mohist universal love. This paper proposes a reading of two famous stories, namely, the story of a young child on the verge of falling into a well, and the story of King Xuan of Qi sparing an ox as paradigmatic cases for understanding Mencius’ account of compassion in the political realm. This paper argues that Mencius succeeds in his defense of governance with compassion against the other two extremes of self-love and altruism. To provide an argument for compatibility with egoism or self-love, this paper offers an analysis of Mencius’ idea of the ruler sharing pleasure with his people instead of denying pleasure for himself. In this sense, a good ruler does not need to sacrifice his self-interest. To counter the demand of universal love of the Mohists, Mencius develops a position that the Confucian ideal ruler, while not sacrificing his self-interests, those interests need to be guided and directed by a proper process of moral cultivation of his compassionate heart so that he can readily share his pleasures with all the peoples in his kingdom. These readings indicate Mencius’ expanded argument for political implications of compassion in the moral universe of the Confucian school.
Hypothetical molecular interconnection between type 2 diabetes and dyslexia
Authors: Bülbül Tuğba , Baharlooie Maryam , Safaeinejad Zahra , Gure Ali Osmay , Ghaedi Kamran 
Published: October 2021

Abstract
Background
Dyslexia is one of the most common learning disabilities, especially among children. Type 2 diabetes is a metabolic disorder that affects a large population globally, with metabolic disorders. There have been several genes that are identified as causes of Dyslexia, and in recent studies, it has been found out that some of those genes are also involved in several metabolic pathways. For several years, it has been known that type 2 diabetes causes several neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Furthermore, in several studies, it was suggested that type 2 diabetes also has some associations with learning disabilities. This raises the question of whether “Is there a connection between type 2 diabetes and dyslexia?”. In this study, this question is elaborated by linking their developmental processes via bioinformatics analysis about these two diseases individually and collectively.

Result
The literature review for dyslexia and type two diabetes was completed. As the result of this literature review, the genes that are associated to type 2 diabetes and dyslexia were identified. The biological pathways of dyslexia, and dyslexia associated genes, type 2 diabetes, and type 2 diabetes associated genes were identified. The association of these genes, regarding to their association with pathways were analysed, and using STRING database the gene associations were analysed and identified.

Conclusion
The findings of this research included the interaction analysis via gene association, co-expression and protein–protein interaction. These findings clarified the interconnection between dyslexia and type 2 diabetes in molecular level and it will be the beginning of an answer regarding to the relationship between T2D and dyslexia. Finally, by improving the understanding this paper aims to open the way for the possible future approach to examine this hypothesis.
Decreased estimated glomerular filtration rate predicts long-term recurrence after catheter ablation of atrial fibrillation in mild to moderate renal insufficiency
Authors: Zheng Jing , Zu Deling , Cheng Keyun , Xia Yunlong , Dong Yingxue , Gao Zhenyan 
Published: October 2021

Abstract
Background
Catheter ablation is an established therapy for atrial fibrillation (AF), but recurrence after ablation remains a great challenge. Additionally, little is known about the effect of renal function on the efficiency of AF ablation. This study aimed to evaluate the predictors of the prognosis of catheter ablation for AF, especially the effect of renal function.

Methods
A total of 306 drug-refractory symptomatic patients with AF who underwent first-time catheter ablation were enrolled in the present study. Individuals underwent circumferential pulmonary vein isolation for paroxysmal AF and stepwise ablation for persistent AF.

Results
The follow-up time was 27.2 ± 19.5 months, 202 patients (66.01%) were free of atrial tachyarrhythmia (non-recurrence group), and the other 104 patients experienced recurrence (recurrence group). The recurrence group had a larger left atrial diameter (LAD) and left atrial volume (LAV), a higher LAV index (LAVI) (both, p < 0.01), and a lower estimated glomerular filtration rate (eGFR) (53.5 ± 14.4 vs. 65.5 ± 13.3 ml/min/1.732, p < 0.001) and creatinine clearance rate (CCr) (85.2 ± 26.1 vs. 101.5 ± 29.4 ml/min, p < 0.05). Multivariate logistic regression indicated both eGFR (p = 0.002) and LAVI (p < 0.001) as independent associated factors for long-term recurrence after single catheter ablation; multivariate Cox proportional hazard regression with backward feature selection identified both eGFR (HR: 0.93, 95% CI: 0.91–0.95, p < 0.001) and LAVI (HR: 1.32, 95% CI: 1.25–1.40, p < 0.001) as independent prognostic factors for recurrence when adjusting other clinical variables.

Conclusions
Decreased eGFR and elevated LAVI may facilitate the long-term recurrence of atrial tachyarrhythmia after catheter ablation for AF.
Physicians’ experiences, attitudes, and beliefs towards medical cannabis: a systematic literature review
Authors: Rønne Sabrina Trappaud , Rosenbæk Frederik , Pedersen Line Bjørnskov , Waldorff Frans Boch , Nielsen Jesper Bo , Riisgaard Helle , Søndergaard Jens 
Published: October 2021

Abstract
Background
An increasing number of countries legalise the use of medical cannabis or allow it for a narrow range of medical conditions. Physicians, and often the patients’ general practitioner, play a major role in implementing this policy. Many of them, however, perceive a lack of evidence-based knowledge and are not confident with providing patients with medical cannabis. The objectives of this review are to synthesise findings about hospital physicians’ and GPs’ experiences, attitudes, and beliefs towards the use of medical cannabis with the purpose of identifying barriers and facilitators towards providing it to their patients.

Methods
Peer-reviewed articles addressing hospital physicians’ and GPs’ experiences, attitudes, and beliefs towards the use of medical cannabis were searched systematically in PubMed, Scopus, EMBASE, and the Cochrane Library.

Results
Twenty-one articles were included from five different countries in which the medical cannabis laws varied. The studied physicians experienced frequent inquiries about medical cannabis from their patients (49–95%), and between 10 and 95% of the physicians were willing to prescribe and/or provide it to the patients, depending on setting, specialty and experience among the physicians. This review found that physicians experienced in prescribing medical cannabis were more convinced of its benefits and less worried about adverse effects than non-experienced physicians. However, physicians specialized in addiction treatment and certain relevant indication areas seemed more sceptical compared to physicians in general. Nevertheless, physicians generally experienced a lack of knowledge of clinical effects including both beneficial and adverse effects.

Conclusion
This review indicates that GPs and hospital physicians from various specialties frequently experience patient demands for medical cannabis and to some degree show openness to using it, although there was a wide gap between studies in terms of willingness to provide. Hospital physicians and GPs’ experienced in prescribing are more convinced of effects and less worried of adverse effects. However, most physicians experience a lack of knowledge of beneficial effects, adverse effects and of how to advise patients, which may comprise barriers towards prescribing. More research, including larger studies with cohort designs and qualitative studies, is needed to further examine facilitators and barriers to physicians’ prescribing practices.
Regional and income disparities in treatment and drug adherence of patients with dyslipidemia: a retrospective cohort study in South Korea, 2003–2015
Authors: Han Kyu-Tae , Choi Dong-Woo , Kim Seungju 
Published: October 2021

Abstract
Backgrounds
Health disparities represent a major public health problem that needs to be addressed, and a variety of factors, including geographical location and income, can contribute to these disparities. Although previous studies have suggested that health differs by region and income, evidence on the difference in treatment rate is relatively insufficient. To identify differences in prescription rates by region and income in patients with dyslipidemia.

Methods
Using data from the National Health Insurance Service senior cohort, we included older adults who were diagnosed with dyslipidemia in Korea from 2003 to 2015. Overall prescription rate was determined for patients with dyslipidemia. In addition, medication possession ratio and a defined daily dose were analyzed in patients who were prescribed statins. A generalized estimating equation Poisson model was used to assess differences in prescription rates.

Results
Patients living in rural areas (Chungcheong-do, Jeolla-do, and Gyeongsang-do) had a significantly higher prescription rate than those in metropolitan cities. Unlike the prescription rate, the drug adherence was significantly higher in Seoul, Gyeonggi-do, and Gangwon-do but lower in Jeolla-do and Gyeongsang-do than in metropolitan cities. Patients with low income had lower prescription rates than those with high income, but this difference was not statistically significant.

Conclusion
Our findings demonstrate differences in the treatment rates of patients with dyslipidemia by region and income. Appropriate interventions are needed in vulnerable regions and groups to increase the treatment rate for patients with dyslipidemia.
Clinical features and prognosis of paediatric rhabdomyosarcoma with bone marrow metastasis: a single Centre experiences in China
Authors: Huang Cheng , Jian Binglin , Su Yan , Xu Na , Yu Tong , He Lejian , Zhang Xue , Liu Yi , Jin Mei , Ma Xiaoli 
Published: October 2021

Abstract
Background
The aim of this study was to summarize the clinical characteristics, therapeutic effects and prognosis of patients with rhabdomyosarcoma (RMS) and bone marrow metastasis, improve the understanding of this disease.

Method
This was a single-institution retrospective study involving the children with RMS, who presented with bone marrow metastasis at initial presentation to our hospital between 1st, Jan, 2006 and 31st, Dec,2019. Follow-up concluded on 31st, Dec, 2020 and the clinical data were collected and analysed.

Result
Between 1st Jan 2006 and 31st Dec 2019, 13 eligible patients presented to our hospital, including 10 males and 3 females, these eligible patients accounted for 4.5% of all RMS patients. The median age at onset was 5.6 years (range 1.7-14 years). The patients not only had unfavourable primary sites, but also had multiple metastases. The bone marrow aspirate samples of the patients comprised 8-95% blast-like cells. Nine of 13 patients were misdiagnosed with haematological malignancies or other solid tumours. With respect to histology, four of 13 children were classified as embryonal RMS and nine as alveolar RMS. Eleven patients underwent PAX-FOXO1 fusion testing; eight had the POX- FOXO1 fusion gene. Immunohistochemically(IHC) analysis revealed that the tumour cells were positive for Desmin, Vimentin, Myo-D1 and Myogenin. More importantly, the patients had extremely poor prognoses, the median EFS was 12.0 months (range 3-28.3 months) and the median OS was 27.0 months (range6-46.2 months).

Conclusion
This study demonstrates that children with RMS and bone marrow metastasis usually exhibit atypical primary sites and multiple metastases, with presentation mimicking haematological malignancies or other solid tumors at initial presentation. Pathology and IHC analysis combined with POX-FOXO1 fusion gene detections can effectively confirm the diagnosis. These patients are more likely to relapse or progress during early treatment and are prone to intracranial metastasis. While multidisciplinary therapy combined with Temozolomide may prevent it, further prospective research is required to evaluate the therapeutic effects.
Recurrent sick leave after COVID-19: investigating the first wave of the pandemic in a comprehensive Swedish registry-based study
Authors: Palstam Annie , Westerlind Emma , Sunnerhagen Katharina S. , Persson Hanna C. 
Published: October 2021

Abstract
Background
Sick-leave due to COVID-19 vary in length and might lead to re-current episodes. The aim was to investigate recurrent sick leave due to COVID-19 during the first wave.

Methods
This is a registry-based cohort study. The study comprises all people with sickness benefit due to COVID-19 in Sweden in March 1–August 31, 2020. Data from the Swedish Social Insurance Agency, the Swedish National Board of Health and Welfare, and Statistics Sweden were merged.

Results
Within the follow-up period of 4 months, 11,955 people were subject to sickness benefit due to COVID-19, whereof 242 people (2.0%) took recurrent sick leave due to COVID-19, and of those 136 (56.2%) remained on sick leave at the end of follow-up. People with recurrent sick leave were older, more often women, and more likely to have been on sick leave prior to the COVID-19 pandemic.

Conclusion
A group of people presented with recurrent sick leave due to COVID-19. For half of them, the second sick leave lasted throughout the follow-up. People with recurrent sick leave differ in several aspects from those with shorter sick leave. To capture long-term sick-leave patterns due to COVID-19, a longer period of follow-up is needed.
Effect of microthread design on the preservation of marginal bone around immediately placed implants: a 5-years prospective cohort study
Authors: Aslroosta Hoori , Akbari Solmaz , Naddafpour Nima , Adnaninia Seyed Taha , Khorsand Afshin , Namadmalian Esfahani Niusha 
Published: October 2021

Abstract
Background
This study aimed to evaluate the effect of the microthread design at the implant neck on the preservation of marginal bone around immediately-placed implants in a 5-year follow up.

Methods
Thirty patients received 41 immediately placed implants which were randomly assigned to treatment groups with microthreaded implants (test group, n = 22) or threaded implants (control group, n = 19). Clinical and radiographic analyses were carried out after 1 and5 years. Plaque index, bleeding on probing, suppuration, probing depth and marginal bone loss were subject to evaluations. The results were analyzed with the T-test, Fisher’s exact test and Mann–Whitney U test.

Results
No implants failed; thirty-five implants (in 27 patients); 21 microthreaded and 14 threaded implants; completed the 5 year follow up. The mean values of the marginal bone loss in microthreaded and threaded groups were 1.12 ± 0.95 mm and 0.87 ± 0.78 mm, respectively during an observation period of 70.9 ± 10.4 months; the differences in marginal bone loss and other pre-implant parameters were not significant between groups (P > 0.05).

Conclusion
Both implant designs showed acceptable results in terms of the clinical parameters and marginal bone level. Within the limitation of this study, the results did not demonstrate any superiority of the microthread design compared to threaded one in marginal bone preservation around immediately placed implants over 5 years of loading.
Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients
Authors: Chou Ruey-Hsing , Wu Po-Shan , Wang Shen-Chih , Wu Cheng-Hsueh , Lu Shu-Fen , Lien Ru-Yu , Tsai Yi-Lin , Lu Ya-Wen , Kuo Ming-Ren , Guo Jiun-Yu , Chou Ruey-Yi , Huang Po-Hsun , Lin Shing-Jong 
Published: October 2021

Abstract
Background
Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU).

Methods
Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG).

Results
Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 μmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 μmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21–5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status.

Conclusion
Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.