bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome
Authors: De Nittis Pasquelena , Efthymiou Stephanie , Sarre Alexandre , Guex Nicolas , Chrast Jacqueline , Putoux Audrey , Sultan Tipu , Raza Alvi Javeria , ur Rahman Zia , Zafar Faisal , Rana Nuzhat , Rahman Fatima , Anwar Najwa , Maqbool Shazia , Zaki Maha S , Gleeson Joseph G , Murphy David , Galehdari Hamid , Shariati Gholamreza , Mazaheri Neda , Sedaghat Alireza ,   SYNAPS Study Group, Lesca Gaetan , Chatron Nicolas , Salpietro Vincenzo , Christoforou Marilena , Houlden Henry , Simonds William F , Pedrazzini Thierry , Maroofian Reza , Reymond Alexandre 
Published: November 2020

BackgroundPathogenic variants ofGNB5encoding the β5subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia.MethodsWe used echocardiography and telemetric ECG recordings to investigate consequences ofGnb5loss in mouse.ResultsWe delineated a key role ofGnb5in heart sinus conduction and showed thatGnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance.Gnb5−/−mice were smaller and had a smaller heart thanGnb5+/+andGnb5+/−, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR inGnb5−/−mice. In contrast,Gnb5−/−mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. HomozygousGnb5loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients.ConclusionsOur data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations inGnb5−/−mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism ofGnb5signalling in the autonomic control of the heart will pave the way for future drug screening.
Proca tubes with the flux of the longitudinal chromoelectric field and the energy flux/momentum density
Authors: Dzhunushaliev Vladimir , Folomeev Vladimir 
Published: November 2020

AbstractWe consider non-Abelian SU(3) Proca theory with a Higgs scalar field included. Cylindrically symmetric solutions describing classical tubes either with the flux of a longitudinal electric field or with the energy flux (and hence with nonzero momentum density) are obtained. It is shown that, in quantum Proca theory, there can exist tubes both with the flux of the longitudinal electric field and with the energy flux/momentum density simultaneously. An imaginary particle – Proca proton – in which ‘quarks’ are connected by tubes with nonzero momentum density is considered. It is shown that this results in the appearance of the angular momentum related to the presence of the non-Abelian electric and magnetic fields in the tube, and this angular momentum is a part of the Proca proton spin.
SCIRT lncRNA Restrains Tumorigenesis by Opposing Transcriptional Programs of Tumor-Initiating Cells
Authors: Zagorac Sladjana , de Giorgio Alex , Dabrowska Aleksandra , Kalisz Mark , Casas-Vila Nuria , Cathcart Paul , Yiu Angela , Ottaviani Silvia , Degani Neta , Lombardo Ylenia , Tweedie Alistair , Nissan Tracy , Vance Keith W. , Ulitsky Igor , Stebbing Justin , Castellano Leandro 
Published: November 2020

Abstract

In many tumors, cells transition reversibly between slow-proliferating tumor-initiating cells (TIC) and their differentiated, faster-growing progeny. Yet, how transcriptional regulation of cell-cycle and self-renewal genes is orchestrated during these conversions remains unclear. In this study, we show that as breast TIC form, a decrease in cell-cycle gene expression and increase in self-renewal gene expression are coregulated by SOX2 and EZH2, which colocalize at CpG islands. This pattern was negatively controlled by a novel long noncoding RNA (lncRNA) that we named Stem Cell Inhibitory RNA Transcript (SCIRT), which was markedly upregulated in tumorspheres but colocalized with and counteracted EZH2 and SOX2 during cell-cycle and self-renewal regulation to restrain tumorigenesis. SCIRT specifically interacted with EZH2 to increase EZH2 affinity to FOXM1 without binding the latter. In this manner, SCIRT induced transcription at cell-cycle gene promoters by recruiting FOXM1 through EZH2 to antagonize EZH2-mediated effects at target genes. Conversely, on stemness genes, FOXM1 was absent and SCIRT antagonized EZH2 and SOX2 activity, balancing toward repression. These data suggest that the interaction of an lncRNA with EZH2 can alter the affinity of EZH2 for its protein-binding partners to regulate cancer cell state transitions.

Significance:
These findings show that a novel lncRNA SCIRT counteracts breast tumorigenesis by opposing transcriptional networks associated with cell cycle and self-renewal.
See related commentary by Pardini and Dragomir, p. 535
Adding Rigor to Biomarker Evaluations—EDRN Experience
Authors: Feng Ziding , Pepe Margaret S. 
Published: November 2020

Abstract
The cancer early-detection biomarker field was, compared with the therapeutic arena, in its infancy when the Early Detection Research Network (EDRN) was initiated in 2000. The EDRN has played a crucial role in changing the culture and the ways people conduct biomarker studies. The EDRN proposed biomarker developmental guidelines and biomarker pivotal trial study design standards, created biomarker reference sets and functioned as an unbiased broker for the field, implemented the most rigorous blinding policy in the biomarker field, developed an array of statistical and computational tools for early-detection biomarker evaluations, and developed a multidisciplinary team-science approach. We reviewed these contributions made by the EDRN and their impacts on maturing the field. Future challenges and opportunities in cancer early-detection biomarker translational research are discussed, particularly in strengthening biomarker discovery pipeline and conducting more efficient biomarker validation studies.
See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”
Phase II Study of Avelumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib
Authors: Lee Dae-Won , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Yoon Jun , Yoon Jung-Hwan , Kim Tae-Yong , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Lee Youngeun , Kim Haeryoung , Lee Kyung-Hun 
Published: November 2020

Abstract

Purpose:
This study investigated the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with advanced hepatocellular carcinoma previously treated with sorafenib (NCT03389126).

Patients and Methods:
This is a single-arm, single center, phase II trial. Patients with Child-Pugh A score who had at least one measurable lesion were enrolled. Intravenous avelumab 10 mg/kg every 2 weeks was given until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to RECIST v1.1. Secondary endpoints included time to progression (TTP), overall survival (OS), disease control rate (DCR), and safety.

Results:
A total of 30 patients were enrolled. After a median follow-up of 13.9 months, 27 progression events and 20 death events occurred. There was no complete response, three (10.0%) partial responses, and 19 patients (63.3%) with stable disease. ORR was 10.0% and DCR was 73.3%. The median TTP and OS was 4.4 and 14.2 months, respectively. PD-L1 expression did not affect avelumab response. Prior duration of sorafenib treatment, when dichotomized by the median 2.7 months, was associated with treatment outcome. TTP (6.5 vs. 1.8 months, P = 0.007) and OS (19.0 vs. 7.8 months, P = 0.006) were superior in patients with longer sorafenib duration. There was tendency of higher ORR (20.0% vs. 0.0%, P = 0.22) in those with longer sorafenib duration. Avelumab was well tolerated with seven grade 3 adverse events and no grade 4 adverse events.

Conclusions:
Avelumab showed moderate efficacy and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.
One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients
Authors: Kandzari David E. , Kirtane Ajay J. , Windecker Stephan , Latib Azeem , Kedhi Elvin , Mehran Roxana , Price Matthew J. , Abizaid Alexandre , Simon Daniel I. , Worthley Stephen G. , Zaman Azfar , Choi James W. , Caputo Ronald , Kanitkar Mihir , McLaurin Brent , Potluri Srinivasa , Smith Timothy , Spriggs Douglas , Tolleson Thaddeus , Nazif Tamim , Parke Maria , Lee Lilian C. , Lung Te-Hsin , Stone Gregg W. ,   for the Onyx ONE US/Japan Investigators
Published: November 2020

Background:
Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients.

Methods:
Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention.

Results:

Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (
P
<0.001).

Conclusions:
Among HBR patients who were event free before DAPT discontinuation at 1 month, favorable safety and effectiveness through 1 year support treatment with Resolute Onyx drug-eluting stents as part of an individualized strategy for shortened DAPT duration following percutaneous coronary intervention.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier NCT03647475.
Incorporating Latent Variables Using Nonnegative Matrix Factorization Improves Risk Stratification in Brugada Syndrome
Authors: Tse Gary , Zhou Jiandong , Lee Sharen , Liu Tong , Bazoukis George , Mililis Panagiotis , Wong Ian C. K. , Chen Cheng , Xia Yunlong , Kamakura Tsukasa , Aiba Takeshi , Kusano Kengo , Zhang Qingpeng , Letsas Konstantinos P. 
Published: November 2020

Background
A combination of clinical and electrocardiographic risk factors is used for risk stratification in Brugada syndrome. In this study, we tested the hypothesis that the incorporation of latent variables between variables using nonnegative matrix factorization can improve risk stratification compared with logistic regression.

Methods and Results

This was a retrospective cohort study of patients presented with Brugada electrocardiographic patterns between 2000 and 2016 from Hong Kong, China. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation. The external validation cohort included patients from 3 countries. A total of 149 patients with Brugada syndrome (84% males, median age of presentation 50 [38–61] years) were included. Compared with the nonarrhythmic group (n=117, 79%), the spontaneous ventricular tachycardia/ ventricular fibrillation group (n=32, 21%) were more likely to suffer from syncope (69% versus 37%,
P
=0.001) and atrial fibrillation (16% versus 4%,
P
=0.023) as well as displayed longer QTc intervals (424 [399–449] versus 408 [386–425];
P
=0.020). No difference in QRS interval was observed (108 [98–114] versus 102 [95–110],
P
=0.104). Logistic regression found that syncope (odds ratio, 3.79; 95% CI, 1.64–8.74;
P
=0.002), atrial fibrillation (odds ratio, 4.15; 95% CI, 1.12–15.36;
P
=0.033), QRS duration (odds ratio, 1.03; 95% CI, 1.002–1.06;
P
=0.037) and QTc interval (odds ratio, 1.02; 95% CI, 1.01–1.03;
P
=0.009) were significant predictors of spontaneous ventricular tachycardia/ventricular fibrillation. Increasing the number of latent variables of these electrocardiographic indices incorporated from n=0 (logistic regression) to n=6 by nonnegative matrix factorization improved the area under the curve of the receiving operating characteristics curve from 0.71 to 0.80. The model improves area under the curve of external validation cohort (n=227) from 0.64 to 0.71.

Conclusions
Nonnegative matrix factorization improves the predictive performance of arrhythmic outcomes by extracting latent features between different variables.
Shared Decisions: A Qualitative Study on Clinician and Patient Perspectives on Statin Therapy and Statin‐Associated Side Effects
Authors: Ahmed Sarah T. , Akeroyd Julia M. , Mahtta Dhruv , Street Richard , Slagle Jason , Navar Ann Marie , Stone Neil J. , Ballantyne Christie M. , Petersen Laura A. , Virani Salim S. 
Published: November 2020

Background
Despite guideline recommendations and clinical trial data suggesting benefit, statin therapy use in patients with atherosclerotic cardiovascular disease remains suboptimal. The aim of this study was to understand clinician and patient views on statin therapy, statin‐associated side effects (SASEs), SASE management, and communication around statin risks and benefits.

Methods and Results
We conducted qualitative interviews of patients with atherosclerotic cardiovascular disease who had SASEs (n=17) and clinicians who regularly prescribe statins (n=20). We used directed content analysis, facilitated by Atlas.ti software, to develop and revise codebooks for clinician and patient interviews. The most relevant codes were “pile sorted” into 5 main topic domains: (1) SASEs vary in severity, duration, and time of onset; (2) communication practices by clinicians around statins and SASEs are variable and impacted by clinician time limitations and patient preconceived notions of SASEs; (3) although a “trial and error” approach to managing SASEs may be effective in allowing clinicians to keep patients with atherosclerotic cardiovascular disease on a statin, it can be frustrating for patients; (4) outside sources, such as the media, internet, social networks, and social circles, influence patients' perceptions and often impact the risk benefit discussion; and (5) a decision aid would be beneficial in facilitating clinician decision‐making around SASEs and discussion of SASEs with the patients.

Conclusions
Statin use among patients with atherosclerotic cardiovascular disease remains suboptimal because of various patient‐ and clinician‐related factors. The development of a decision aid to facilitate discussion of SASEs, clinician decision‐making, and SASE management may improve statin use in this high‐risk population.
Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
Authors: Wada Hiromichi , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , Shimizu Masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Iguchi Moritake , Masunaga Nobutoyo , Ishii Mitsuru , Yamakage Hajime , Kusakabe Toru , Yasoda Akihiro , Shimatsu Akira , Kotani Kazuhiko , Satoh‐Asahara Noriko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji ,   for the ANOX Study Investigators
Published: November 2020

Background
Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear.

Methods and Results
Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers.

Conclusions
Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.
Diet, ontogenetic changes and rhythm of feeding activities in Macrobrachium macrobrachion (Herklots, 1851) (Decapoda, Palaemonidae) in the waterbodies and rivers of Benin, West Africa
Authors: Koussovi G. , Niass F. , Allozounhoue C. J. , Dahouda M. , Bonou C. A. , Montchowui E. 
Published: November 2020

Abstract
Knowledge of the diet of Macrobrachium macrobrachion (Herklots, 1851) in its natural environment is a key factor facilitating its successful breeding. We have analysed the stomach content of 452 specimens collected from the Ouémé River Delta (ORD) (338 stomachs) and from the Mono River/Grand-Popo Lagoon complex (MGLC) (114 stomachs), from February to October 2016. The analysis enables to calculate the coefficient of vacuity for the ORD (3.50%) and for the MGLC (3.50%). The results show that M. macrobrachion has a detritivore-omnivore type of diet, feeding mainly on phytoplankton (diatoms and cyanophytes) and detritus. However, the diet of the young shrimps, composed mostly of insect larvae, differs from that of adult. In the adult M. macrobrachion, the pace of feeding activities is greatest in the morning (6.00 to 9.00 am), low in middle of the day (10.00 am to 13.00 pm), and there is a slight trophic activity between 17.00 and 22.00 pm. Outside of the above periods, i.e., from 14.00 to 16.00 pm and 23.00 pm to 5.00 am, the species is at rest. Juveniles feed at dawn. In the nighttime and at dusk, groups of shrimps of varying sizes do feed. The findings of this study suggest that live prey is the best feed for the larvae of M. macrobrachion in captivity and should be distributed preferably early in the morning.
Stygofauna of Oman, 8. The Thermosbaenacea collected during the biological groundwater survey of Oman of 1996
Authors: Wagner H. P. 
Published: November 2020

Abstract
Four species of the thermosbaenacean genus Tethysbaena Wagner, 1994 are described from Oman as T. barbatula n. sp., T. tristani n. sp., T. cryptofallax n. sp. and T. spec. from four isolated groundwater aquifers north and south of the Hajar Mountains in the north and two small isolated aquifers near Salalah and Marbat in the south. It is suggested that the speciation into these separate species is due to regressions of the Tethys Sea. The rising of dry land (mountain ridges) some time at the Oligocene-Miocene boundary would have constituted major barriers for isolated populations of the ancestral species. Not only morphological differences support the specific division into species, also the results of a DNA analysis from an earlier study by Cánovas et al. (2016) clearly support the present division into two localized, isolated species in the southern part of Oman.
The EU Response to Criminal Misuse of Cryptocurrencies: The Young, already Outdated 5th Anti-Money Laundering Directive
Authors: Covolo Valentina 
Published: November 2020

Abstract
Combatting criminal misuse of cryptocurrencies was at the core of the fatf agenda under the US Presidency, culminating in June 2019 with the thorough extension of international standards against money laundering over virtual assets’ markets. This echoed the first legislative measure regulating virtual currencies adopted by the EU a year before. Directive 2018/843, better known as the 5th Anti-Money Laundering Directive, fails however to address key technological breakthroughs and new business models, which continuously make the ever-growing and fast-paced crypto economy evolve. Against this background, the present contribution investigates shortfalls and challenges that lay ahead in the light of the new fatf Recommendations. It ultimately argues that the preventive anti-money laundering measures cannot dispense with the establishment of a cross-border integrated supervisory and enforcement system.
A note on the order of constituents in the Mehri Noun Phrase
Authors: Shlonsky Ur 
Published: November 2020

Abstract
Data elicited from native speakers of Mehri and, to a lesser extent, Jibbali—two extant Modern South Arabian languages—show that within the extended nominal phrase, the noun precedes adjectives and the numerals one and two, but follows numerals from three up. This yields the following order: Num≥3 >> Noun >> Num=1,2 >> Adjective. Demonstratives appear between the noun and the numerals one or two, Noun >> Dem >> Num=1,2 >> Adjective, but when the noun is preceded by numerals from three up, the order is Dem >> Num≥3 >> Noun >> Adjective. Following Cinque (2005), I argue that these orders can be explained by taking the constituent order derived by external merge to be Dem >> Num≥3 >> Num=1,2 >> Adjective >> Noun and having the noun (more precisely, the minimal noun phrase) move step-by-step to a position immediately above, and therefore to the left of Num=1,2. The noun cannot move above Num≥3 and since it cannot skip it, it also remains below Dem.