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To examine the effectiveness of a nicotine patch worn for four weeks before a quit attempt.


The study of systems with fractional charges and spins has become an extremely important tool to understand errors in approximate electronic structure methods, particularly in the context of density functional theory. Meanwhile, similar studies with wavefunction (WF)-based methods beyond second-order perturbation theory have been lacking. In this contribution, we study the performance of different coupled cluster (CC) and many-body perturbation theory (MBPT)-based methods for fractional charges. The use of the conventional and renormalized formulations of fractional-charge MBPT is discussed. The fractional spin behavior of the coupled cluster doubles (CCD) method is also investigated. Overall, all tested WF methods show very promising performance for the fractional charge problem. CCD is also quite accurate for the fractional spin problem in He+ across most of the range, although it breaks down to near Hartree-Fock quality in the strongly correlated limit. Beyond the study of fractional charge and spin curves, the implementation of CC methods with fractional occupation numbers offers a promising route to treating problems with multi-reference character in a single-reference framework.


It is not yet established the advantages between amphotericin B lipid complex (ABLC) and liposomal (L-AmB) in patients with invasive fungal infections refractory to usual doses of conventional AmB (d-AmB), previous renal impairment, or unacceptable d-AmB renal toxicity. This systematic review aims to compare ABLC and L-AmB effectiveness and safety outcomes in these subgroups of patients.


Multi-omics studies promise the improved characterization of biological processes across molecular layers. However, methods for the unsupervised integration of the resulting heterogeneous data sets are lacking. We present Multi-Omics Factor Analysis (MOFA), a computational method for discovering the principal sources of variation in multi-omics data sets. MOFA infers a set of (hidden) factors that capture biological and technical sources of variability. It disentangles axes of heterogeneity that are shared across multiple modalities and those specific to individual data modalities. The learnt factors enable a variety of downstream analyses, including identification of sample subgroups, data imputation and the detection of outlier samples. We applied MOFA to a cohort of 200 patient samples of chronic lymphocytic leukaemia, profiled for somatic mutations, RNA expression, DNA methylation and ex vivo drug responses. MOFA identified major dimensions of disease heterogeneity, including immunoglobulin heavy-chain variable region status, trisomy of chromosome 12 and previously underappreciated drivers, such as response to oxidative stress. In a second application, we used MOFA to analyse single-cell multi-omics data, identifying coordinated transcriptional and epigenetic changes along cell differentiation.


To examine the effect on the trade in opioids through online illicit markets (“cryptomarkets”) of the US Drug Enforcement Administration’s ruling in 2014 to reschedule hydrocodone combination products.


The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model-guided framework to predict higher-dimensional consortia from time-resolved measurements of lower-order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi-species community dynamics, as opposed to higher-order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history-dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human-associated intestinal species and illuminated design principles of microbial communities.


To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia.


To evaluate the effectiveness of telephone health coaching delivered by a nurse to support self management in a primary care population with mild symptoms of chronic obstructive pulmonary disease (COPD).


Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson’s trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ(2)=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ(2)=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion: Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.


Objective: To observe the effects of recombinant adenovirus with human thioredoxin (hTRX) on the inflammatory response in mice with viral myocarditis and explore the related mechanism. Methods: Sixty Balb/c male mice were randomly divided into control group, myocarditis group, and hTRX group according to the random number table (n=20 each group). The myocarditis group and hTRX group were injected with 100 TCID(50) Coxackie virus B3 (0.1 ml) in the abdomen and control group were injected with saline. Two days before the viral injection, the hTRX group were injected with recombinant adenovirus vector coding the human thioredoxin gene by pericardial puncture and the control group and myocarditis group were injected with recombinant adenovirus vector without coding gene by pericardial puncture, all these mice were killed and hearts were removed 7 days later. The morphology of myocardial tissue in each group was detected by HE staining and the ultrastructure changes by electron microscope. The protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and NF-κB were detected by ELISA and Western blot. Immunohistochemical staining was performed to observe the protein expression levels of thioredoxin. Results: Necrosis of myocardial cells and a small amount of cell infiltration were found in the myocarditis group and necrosis and cell infiltration were significantly reduced in the hTRX group and no myocardial lesion was found in control group on HE stained sections. Electron microscope examination evidenced cell swelling and dissolved myofilament, vacuoles degeneration in mitochondria in the myocarditis group. These changes were significantly reduced in the hTRX group. There was no myocardial lesion in control group. The protein expression of TNF-α, IL-1β and NF-κB were significantly upregulated in myocarditis group than in control group (all P<0.01). The protein expression of TNF-α, IL-1β and NF-κB were significantly downregulated in hTRX group than in myocarditis group (all P<0.01). Immunohistochemical staining showed that protein expression of hTRX was higher in hTRX group than in myocarditis group (P<0.01). Conclusion: Recombinant adenovirus hTRX can attenuate cardiac injury in mice with acute myocarditis via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-1β and NF-κB.