We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Fast radio bursts (FRBs) are millisecond-duration radio transients
of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star ...magnetospheres
or relativistic shocks far from the central energy source
. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters
or variable polarization angles in some other apparently one-off events
. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.
The response to lithium for the treatment of bipolar disease is variable. This genetic study showed a strong association between variants in
GADL1
and response to treatment in Han Chinese patients ...with bipolar I disease.
Bipolar disorder is a disabling mental illness that is characterized by episodes of both elevated or irritable mood and depression.
1
,
2
Currently, lithium is the first-line choice for maintenance treatment of bipolar disorder and reduces the risks of relapse and suicide.
3
–
5
Approximately 80% of patients with bipolar I disorder who are treated with lithium over the long term have at least a partial response,
6
and 30% have an excellent response
7
,
8
with complete remission of symptoms observed in populations of patients of European descent.
Clinical predictors of a good response to lithium treatment have been reported, such as age . . .
Summary
Is gout a risk factor for future osteoporosis? This large population-based study comprising two matched groups of individuals with and without gout demonstrates that patients with gout have a ...20% increase in the risk of developing osteoporosis in future through an 8-year follow-up.
Introduction
To examine if gout is associated with an increased risk of osteoporosis.
Methods
We conducted a nationwide population-based retrospective matched-cohort study. Two matched cohorts (
n
= 36,458 with gout and 71,602 without gout) assembled and recruited from the Longitudinal Health Insurance Dataset containing 1 million subjects. Exclusion criteria were missing data, age < 20 years, short follow-up period, and pre-existing osteoporosis. Both cohorts were followed up until incident osteoporosis, death, or the end of the study. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for socioeconomic proxy, geographical difference, glucocorticoid and allopurinol exposure, various prespecified medical conditions, and comorbidities.
Results
Men comprised 72.8% of the cohorts. With a follow-up of 183,729 and 359,900 person-years for the gout and non-gout cohorts, 517 and 811 incidents of osteoporosis occurred, respectively, after excluding osteoporosis incidents in the first 3 years of follow-up. The cumulative incidence of osteoporosis was statistically higher in the gout cohort than in the non-gout cohort, at 3.3 versus 2.1% (
P
= 0.0036, log-rank). Our Cox model showed a 1.2-fold increase in the incidence of osteoporosis in the gout cohort, with an aHR of 1.2 (95% confidence interval, 1.06–1.35).
Conclusions
This first population-based epidemiologic study supports the hypothesis that compared with individuals without gout; those with gout have a modest increase in the risk of developing osteoporosis in future.
The authors examine the impact that oxygenated volatile organic compounds have on air quality and climate. Topics discussed include ozonolysis of halides at the Sea surface and halogenation of ...dissolved organic matter (DOM) by radical and nonradical RHS.
Summary
Background Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking.
Objectives To provide a meta‐analysis evidence‐based ...examination of IVIg efficacy against TEN.
Methods A systematic review and meta‐analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high‐dose and low‐dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg.
Results Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19·9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1·00 95% confidence interval (CI) 0·58–1·75; P = 0·99. The pooled OR for mortality in patients treated with high‐dose IVIg vs. supportive care was 0·63 (95% CI 0·27–1·44; P = 0·27). Adults treated with high‐dose IVIg exhibited significantly lower mortality than those treated with low‐dose IVIg (18·9% vs. 50%, respectively; P = 0·022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0·494; 95% CI 0·106–2·300; P = 0·369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21·6%; P = 0·001).
Conclusions Although high‐dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.
See also the Commentary by Walsh and Creamer
Background and purpose
Physical activity is associated with a reduced incidence of first‐time stroke. However, few studies have examined the effect of pre‐stroke physical activity on post‐stroke ...complications and clinical outcomes.
Methods
A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre‐stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure‐time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups.
Results
The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post‐stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post‐stroke.
Conclusion
Dedicated leisure‐time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post‐stroke complications, lower mortality and better outcomes.
Abstract
Motivation
Sequence-based protein–protein interaction (PPI) prediction represents a fundamental computational biology problem. To address this problem, extensive research efforts have been ...made to extract predefined features from the sequences. Based on these features, statistical algorithms are learned to classify the PPIs. However, such explicit features are usually costly to extract, and typically have limited coverage on the PPI information.
Results
We present an end-to-end framework, PIPR (Protein–Protein Interaction Prediction Based on Siamese Residual RCNN), for PPI predictions using only the protein sequences. PIPR incorporates a deep residual recurrent convolutional neural network in the Siamese architecture, which leverages both robust local features and contextualized information, which are significant for capturing the mutual influence of proteins sequences. PIPR relieves the data pre-processing efforts that are required by other systems, and generalizes well to different application scenarios. Experimental evaluations show that PIPR outperforms various state-of-the-art systems on the binary PPI prediction problem. Moreover, it shows a promising performance on more challenging problems of interaction type prediction and binding affinity estimation, where existing approaches fall short.
Availability and implementation
The implementation is available at https://github.com/muhaochen/seq_ppi.git.
Supplementary information
Supplementary data are available at Bioinformatics online.
Summary
Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The ...TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.
Introduction
Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae.
Methods
We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS.
Results
A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (
p
< 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity.
Conclusion
Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.
The first self-consistent simulations of electron acceleration during magnetic reconnection in a macroscale system are presented. Consistent with solar flare observations, the spectra of energetic ...electrons take the form of power laws that extend more than two decades in energy. The drive mechanism for these nonthermal electrons is Fermi reflection in growing and merging magnetic flux ropes. A strong guide field suppresses the production of nonthermal electrons by weakening the Fermi drive mechanism. For a weak guide field the total energy content of nonthermal electrons dominates that of the hot thermal electrons even though their number density remains small. Our results are benchmarked with the hard x-ray, radio, and extreme ultraviolet observations of the X8.2-class solar flare on September 10, 2017.
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