"Internet Gaming Disorder" in China: Biomedical Sickness or Sociological Badness?

Trent M. Bax SAGE 2015 SAGE Open Vol.10 No.1

Quantitative Residue-Specific Protein Backbone Torsion Angle Dynamics from Concerted Measurement of ³<i>J</i> Couplings

Lee, Jung Ho,Li, Fang,Grishaev, Alexander,Bax, Ad American Chemical Society 2015 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.137 No.4

<P>Three-bond <SUP>3</SUP><I>J</I><SUB>C′C′</SUB> and <SUP>3</SUP><I>J</I><SUB>HNHα</SUB> couplings in peptides and proteins are functions of the intervening backbone torsion angle ϕ. In well-ordered regions, <SUP>3</SUP><I>J</I><SUB>HNHα</SUB> is tightly correlated with <SUP>3</SUP><I>J</I><SUB>C′C′</SUB>, but the presence of large ϕ angle fluctuations differentially affects the two types of couplings. Assuming the ϕ angles follow a Gaussian distribution, the width of this distribution can be extracted from <SUP>3</SUP><I>J</I><SUB>C′C′</SUB> and <SUP>3</SUP><I>J</I><SUB>HNHα</SUB>, as demonstrated for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins, slow transverse relaxation permits measurement of <SUP>3</SUP><I>J</I><SUB>C′C′</SUB> and <SUP>3</SUP><I>J</I><SUB>HNH</SUB> couplings at very high precision, and impact of factors other than the intervening torsion angle on <SUP>3</SUP><I>J</I> will be minimal, making these couplings exceptionally valuable structural reporters. Analysis of α-synuclein yields rather homogeneous widths of 69 ± 6° for the ϕ angle distributions and <SUP>3</SUP><I>J</I><SUB>C′C′</SUB> values that agree well with those of a recent maximum entropy analysis of chemical shifts, <I>J</I> couplings, and <SUP>1</SUP>H–<SUP>1</SUP>H NOEs. Data are consistent with a modest (≤30%) population of the polyproline II region.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2015/jacsat.2015.137.issue-4/ja512593s/production/images/medium/ja-2014-12593s_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja512593s'>ACS Electronic Supporting Info</A></P>

Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

Chang, Hyuk-Jae,Lin, Fay Y.,Lee, Sang-Eun,Andreini, Daniele,Bax, Jeroen,Cademartiri, Filippo,Chinnaiyan, Kavitha,Chow, Benjamin J.W.,Conte, Edoardo,Cury, Ricardo C.,Feuchtner, Gudrun,Hadamitzky, Marti Elsevier 2018 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY - Vol.71 No.22

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden.</P> <P><B>Objectives</B></P> <P>The purpose of this study was to identify atherosclerotic features associated with precursors of ACS.</P> <P><B>Methods</B></P> <P>We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs).</P> <P><B>Results</B></P> <P>We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm<SUP>3</SUP> fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm<SUP>3</SUP> necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.</P> <P><B>Conclusions</B></P> <P>Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.</P> <P><B>Central Illustration</B></P> <P>[DISPLAY OMISSION]</P>

MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data

Mantsyzov, Alexey B.,Shen, Yang,Lee, Jung Ho,Hummer, Gerhard,Bax, Ad Springer-Verlag 2015 Journal of biomolecular NMR Vol.63 No.1

<P>MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver that generates residue-by-residue Ramachandran map distributions for disordered proteins or disordered regions in proteins on the basis of experimental NMR parameters. As input data, the program currently utilizes up to 12 different parameters. These include three different types of short-range NOEs, three types of backbone chemical shifts ((15)N, (13)C(관), and (13)C'), six types of J couplings ((3)JHNH관, (3)JC'C', (3)JC'H관, (1)JH관C관, (2)JC관N and (1)JC관N), as well as the (15)N-relaxation derived J(0) spectral density. The Ramachandran map distributions are reported in terms of populations of their 15°??????15° voxels, and an adjustable maximum entropy weight factor is available to ensure that the obtained distributions will not deviate more from a newly derived coil library distribution than required to account for the experimental data. MERA output includes the agreement between each input parameter and its distribution-derived value. As an application, we demonstrate performance of the program for several residues in the intrinsically disordered protein 관-synuclein, as well as for several static and dynamic residues in the folded protein GB3.</P>

Prognostic value of chronic total occlusions detected on coronary computed tomographic angiography

Opolski, Maksymilian P,Gransar, Heidi,Lu, Yao,Achenbach, Stephan,Al-Mallah, Mouaz H,Andreini, Daniele,Bax, Jeroen J,Berman, Daniel S,Budoff, Matthew J,Cademartiri, Filippo,Callister, Tracy Q,Chang, Hy BMJ Group 2019 Heart Vol.105 No.3

<P><B>Objective</B></P><P>Data describing clinical relevance of chronic total occlusion (CTO) identified by coronary CT angiography (CCTA) have not been reported to date. We investigated the prognosis of CTO on CCTA.</P><P><B>Methods</B></P><P>We identified 22 828 patients without prior known coronary artery disease (CAD), who were followed for a median of 26 months. Based on CCTA, coronary lesions were graded as normal (no atherosclerosis), non-obstructive (1%–49%), moderate-to-severe (50%–99%) or totally occluded (100%). All-cause mortality, and major adverse cardiac events defined as mortality, non-fatal myocardial infarction and late coronary revascularisation (≥90 days after CCTA) were assessed.</P><P><B>Results</B></P><P>The distribution of patients with normal coronaries, non-obstructive CAD, moderate-to-severe CAD and CTO was 10 034 (44%), 7965 (34.9%), 4598 (20.1%) and 231 (1%), respectively. The mortality rate per 1000 person-years of CTO patients was non-significantly different from patients with moderate-to-severe CAD (22.95; 95% CI 12.71 to 41.45 vs 14.46; 95% CI 12.34 to 16.94; p=0.163), and significantly higher than of those with normal coronaries and non-obstructive CAD (p<0.001 for both). Among 14 382 individuals with follow-up for the composite end point, patients with CTO had a higher rate of events than those with moderate-to-severe CAD (106.56; 95% CI 76.51 to 148.42 vs 65.45; 95% CI 58.01 to 73.84, p=0.009). This difference was primarily driven by an increase in late revascularisations in CTO patients (27 of 35 events). After multivariable adjustment, compared with individuals with normal coronaries, the presence of CTO conferred the highest risk for adverse cardiac events (14.54; 95% CI 9.11 to 23.20, p<0.001).</P><P><B>Conclusions</B></P><P>The detection of CTO on non-invasive CCTA is associated with increased rate of late revascularisation but similar 2-year mortality as compared with moderate-to-severe CAD.</P><P><B>Trial registration number</B></P><P> NCT01443637.</P>