Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs

Enhancing the lateral-flow immunoassay for viral detection using an aqueous two-phase micellar system

Availability of a rapid, accurate, and reliable point-of-care (POC) device for detection of infectious agents and pandemic pathogens, such as swine-origin influenza A (H1N1) virus, is crucial for effective patient management and outbreak prevention. Due to its ease of use, rapid processing, and minimal power and laboratory equipment requirements, the lateral-flow (immuno)assay (LFA) has gained much attention in recent years as a possible solution. However, since the sensitivity of LFA has been shown to be inferior to that of the gold standards of pathogen detection, namely cell culture and real-time PCR, LFA remains an ineffective POC assay for preventing pandemic outbreaks. A practical solution for increasing the sensitivity of LFA is to concentrate the target agent in a solution prior to the detection step. In this study, an aqueous two-phase micellar system comprised of the nonionic surfactant Triton X-114 was investigated for concentrating a model virus, namely bacteriophage M13 (M13), prior to LFA. The volume ratio of the two coexisting micellar phases was manipulated to concentrate M13 in the top, micelle-poor phase. The concentration step effectively improved the M13 detection limit of the assay by tenfold from 5 × 108 plaque forming units (pfu)/mL to 5 × 107 pfu/mL. In the future, the volume ratio can be further manipulated to yield a greater concentration of a target virus and further decrease the detection limits of the LFA. Figure A schematic representation of concentrating viruses with an aqueous two-phase micellar system containing Triton X-114 surfactant prior to the detection of the virus through the lateral-flow immunoassa

Methyl 1-(7-acetamido-5,8-dimeth­oxy­quinolin-2-yl)-4-methyl-β-carboline-3-carboxyl­ate

The title compound, C27H24N4O5, is an inter­mediate in the synthesis of lavendamycin via a ruthenium-catalysed [2 + 2 + 2] cyclo­addition. An intra­molecular hydrogen-bond bridge from the carboline to the quinoline stabilizes a highly planar geometry [maximum deviation = 0.065 (6) Å] for the two rigid units. This hydrogen-bond-stabilized coplanarity has a very close analogy in the structure of the anti­tumor anti­biotic streptonigrin in the solid state and in solution. Inter­molecular hydrogen-bond bridges of amides groups along the a axis and π–π stacking inter­actions [centroid–centroid distance = 3.665 (9) Å] connect mol­ecules arranged in a parallel manner

Drop in the hard pulsed fraction and a candidate cyclotron line in IGR J16320-4751 seen by NuSTAR

We report on a timing and spectral analysis of a 50-ks NuSTAR observation of IGR J16320-4751 (= AX J1631.9-4752); a high-mass X-ray binary hosting a slowly-rotating neutron star. In this observation from 2015, the spin period was 1,308.8+/-0.4 s giving a period derivative dP/dt ~ 2E-8 s s-1 when compared with the period measured in 2004. In addition, the pulsed fraction decreased as a function of energy, as opposed to the constant trend that was seen previously. This suggests a change in the accretion geometry of the system during the intervening 11 years. The phase-averaged spectra were fit with the typical model for accreting pulsars: a power law with an exponential cutoff. This left positive residuals at 6.4 keV attributable to the known iron K-alpha line, as well as negative residuals around 14 keV from a candidate cyclotron line detected at a significance of 5-sigma. We found no significant differences in the spectral parameters across the spin period, other than the expected changes in flux and component normalizations. A flare lasting around 5 ks was captured during the first half of the observation where the X-ray emission hardened and the local column density decreased. Finally, the binary orbital period was refined to 8.9912+/-0.0078 d thanks to Swift/BAT monitoring data from 2005-2022.Comment: 17 pages, 11 figures, Referee-revised version accepted for publication in the Astrophysical Journa

Membrane lipid and expression responses of Saccharolobus islandicus REY15A to acid and cold stress

Archaea adjust the number of cyclopentane rings in their glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids as a homeostatic response to environmental stressors such as temperature, pH, and energy availability shifts. However, archaeal expression patterns that correspond with changes in GDGT composition are less understood. Here we characterize the acid and cold stress responses of the thermoacidophilic crenarchaeon Saccharolobus islandicus REY15A using growth rates, core GDGT lipid profiles, transcriptomics and proteomics. We show that both stressors result in impaired growth, lower average GDGT cyclization, and differences in gene and protein expression. Transcription data revealed differential expression of the GDGT ring synthase grsB in response to both acid stress and cold stress. Although the GDGT ring synthase encoded by grsB forms highly cyclized GDGTs with ≥5 ring moieties, S. islandicus grsB upregulation under acidic pH conditions did not correspond with increased abundances of highly cyclized GDGTs. Our observations highlight the inability to predict GDGT changes from transcription data alone. Broader analysis of transcriptomic data revealed that S. islandicus differentially expresses many of the same transcripts in response to both acid and cold stress. These included upregulation of several biosynthetic pathways and downregulation of oxidative phosphorylation and motility. Transcript responses specific to either of the two stressors tested here included upregulation of genes related to proton pumping and molecular turnover in acid stress conditions and upregulation of transposases in cold stress conditions. Overall, our study provides a comprehensive understanding of the GDGT modifications and differential expression characteristic of the acid stress and cold stress responses in S. islandicus

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review

Radioligand therapy with Lutetium-177 (177Lu)-Prostate-specific membrane antigen (PSMA) has shown to prolong survival in metastatic castration resistant prostate cancer (mCRPC). One of the major challenges for clinicians in the future is to select those patients who would benefit most from this therapy to position it in the treatment landscape of mCRPC. This, in turn, will lead to the delivery of personalized therapies. In this narrative review article we summarize recent studies investigating both predictive and prognostic clinical, imaging-based, and molecular biomarkers to predict treatment response to 177Lu-PSMA-617 radioligand therapy with the aim of identifying men who should be considered for this approach. Of note, the evidence on the role of biomarkers currently relies on small retrospective trials and their validation in larger prospective cohorts is necessary before these results can be translated in the clinical practice

New Physics Models of Direct CP Violation in Charm Decays

In view of the recent LHCb measurement of Delta A_CP, the difference between the time-integrated CP asymmetries in D --> K+K- and D --> pi+pi- decays, we perform a comparative study of the possible impact of New Physics degrees of freedom on the direct CP asymmetries in singly Cabibbo suppressed D meson decays. We systematically discuss scenarios with a minimal set of new degrees of freedom that have renormalizable couplings to the SM particles and that are heavy enough such that their effects on the D meson decays can be described by local operators. We take into account both constraints from low energy flavor observables, in particular D0-D0bar mixing, and from direct searches. While models that explain the large measured value for Delta A_CP with chirally enhanced chromomagnetic penguins are least constrained, we identify a few viable models that contribute to the D meson decays at tree level or through loop induced QCD penguins. We emphasize that such models motivate direct searches at the LHC.Comment: 24 pages, 13 figures. v2: typos corrected, reference added, published versio

The fractional amplitude of low-frequency fluctuations signals related to amyloid uptake in high-risk populations—A pilot fMRI study

BackgroundPatients with type 2 diabetes mellitus (T2DM) and subjective cognitive decline (SCD) have a higher risk to develop Alzheimer's Disease (AD). Resting-state-functional magnetic resonance imaging (rs-fMRI) was used to document neurological involvement in the two groups from the aspect of brain dysfunction. Accumulation of amyloid-β (Aβ) starts decades ago before the onset of clinical symptoms and may already have been associated with brain function in high-risk populations. However, this study aims to compare the patterns of fractional amplitude of low-frequency fluctuations (fALFF) maps between cognitively normal high-risk groups (SCD and T2DM) and healthy elderly and evaluate the association between regional amyloid deposition and local fALFF signals in certain cortical regions.Materials and methodsA total of 18 T2DM, 11 SCD, and 18 healthy elderlies were included in this study. The differences in the fALFF maps were compared between HC and high-risk groups. Regional amyloid deposition and local fALFF signals were obtained and further correlated in two high-risk groups.ResultsCompared to HC, the altered fALFF signals of regions were shown in SCD such as the left posterior cerebellum, left putamen, and cingulate gyrus. The T2DM group illustrated altered neural activity in the superior temporal gyrus, supplementary motor area, and precentral gyrus. The correlation between fALFF signals and amyloid deposition was negative in the left anterior cingulate cortex for both groups. In the T2DM group, a positive correlation was shown in the right occipital lobe and left mesial temporal lobe.ConclusionThe altered fALFF signals were demonstrated in high-risk groups compared to HC. Very early amyloid deposition in SCD and T2DM groups was observed to affect the neural activity mainly involved in the default mode network (DMN)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin