Waddellkrebs9042

A palladium-catalyzed Heck reaction between 2-oxyacrylates and aryl bromides was developed, where DavePhos was a unique ligand that efficiently promoted the reaction. The products, 2-oxycinnamates, served as excellent precursors, providing synthetically useful monoaryl pyruvates or ortho ester-protected monoaryl pyruvates depending on the nature of the 2-oxy group. The formation of such ortho esters via alkoxide addition is novel, and computational studies identified a plausible mechanism with an oxyallyl zwitterion as the key intermediate.The first atroposelective aminocatalytic methodology for the construction of C-N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C-N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C-N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C3 - and N1 -sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C-N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.Layered two-dimensional dichalcogenides are potential candidates for post-silicon electronics. Here, we report insightfully experimental and theoretical studies on the fundamental Coulomb screening and scattering effects in these correlated systems, in response to the changes of three crucial Coulomb factors, including electric permittivity, interaction distance, and density of Coulomb impurities. We systematically collect and analyze the trends of electron mobility with respect to the above factors, realized by synergic modulations on channel thicknesses and gating modes in dual-gated MoS2 transistors with asymmetric dielectric cleanliness. Strict configurative form factors are developed to capture the subtle parametric changes across dimensional crossover. A full diagram of the carrier scattering mechanisms, in particular on the pronounced Coulomb scattering, is unfolded. Moreover, we clarify the presence of up to 40% discrepancy in mobility by considering the permittivity modification across dimensional crossover. The understanding is useful for exploiting atomically thin body transistors for advanced electronics.The Cu(OTf)2/NBS-mediated tandem reaction of 1-cinnamyl alcohol-o-carboranes for the synthesis of C-alkenyl-o-carboranes has been developed. Mechanism studies demonstrated that the Cu(OTf)2-promoted ring opening of oxetane with electron-rich arenes as soft nucleophiles was involved and was the key step for the transformation. This work provided an alternative strategy for the synthesis of C-alkenyl-o-carboranes, which has an important reference for the synthesis of o-carborane derivatives with diversity.

The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy.

A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval.

A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases.

In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.

In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.

MRI is commonly accepted as the gold standard imaging technique for identification of isolated discoligamentous injury to the cervical spine. Widening of the anterior disc space (ADW) has been suggested as signs of injury to the anterior longitudinal ligament (ALL). see more The purpose of this study aimed to assess the accuracy of ADW reported on CT as a sign of ligamentous injury compared.

The study was performed at a level 1 trauma centre. All patients over a 5-year period from 1 January 2015 to 31 January 2019 who underwent a cervical CT scan for the indication of trauma and who subsequently received a cervical spine MRI during the same admission were included if no fracture was found on the initial CT. Demographic data were collected along with mechanism of injury and time period between CT and MRI. Presence or absence of subjective CT-ADW along with presence or absence of ALL injury on MRI was recorded by retrospective review of the radiology reports. Sensitivity, specificity and positive and negative predictive values were then calculated.

Over a 5-year period, 1,305 patients fulfilled the study criteria. CT-ADW had a sensitivity, specificity and positive predictive value of 8.2% (95% CI 2.7-18.1%), 96.2% (95% CI 95.3-97.4%) and 10.2% (95% CI 3.4-22.2%) respectively.

Subjective CT-ADW is a poor predictor of ALL injury as assessed by MRI and should not be relied upon in isolation to diagnose ligamentous injury of the cervical spine in the setting of trauma.

Subjective CT-ADW is a poor predictor of ALL injury as assessed by MRI and should not be relied upon in isolation to diagnose ligamentous injury of the cervical spine in the setting of trauma.

The purpose of this study was to investigate better radiological prognostic factors in clinical T1 pure-solid non-small cell lung cancer (NSCLC).

This study enrolled 284 patients with clinical T1 solid NSCLC who underwent anatomical lung resection. The Cox proportional hazard model was used to evaluate the prognostic impact of tumor volume doubling time (VDT) at disease-free survival (DFS) and cancer-specific survival (CSS).

The median VDT was 347 days. Age (hazard ratio (HR) = 1.04; 95% confidence interval (CI), 1.01-1.07) and standardized uptake value max (SUVmax) (>6.0) (HR = 2.61; 95% CI, 1.52-4.66) were identified as significantly independent worse prognostic factors for DFS in a multivariable analysis without VDT. Furthermore, a multivariable analysis without SUVmax identified age (HR = 1.06; 95% CI, 1.03-1.09), CEA (>5.0 ng/ml) (HR = 2.34; 95% CI, 1.30-4.02), tumor diameter on CT (>2.0 cm) (HR = 1.91; 95% CI, 1.18-3.13), and VDT (HR = 4.03; 95% CI, 2.41-6.93) as significantly independent worse prognostic factors for DFS.

The VDT value could be a useful prognostic factor in clinical T1 solid NSCLC.

The VDT value could be a useful prognostic factor in clinical T1 solid NSCLC.The photophysical characterization of two dyes used as scintillators, crystalline para-terphenyl and EJ-276, a plastic heavily doped with 2,5-diphenyloxazole (DPO), was investigated with steady-state absorption, time-resolved emission, and transient absorption at room and cryogenic temperatures. Application of time-gated emission spectroscopy allowed for the measurement of phosphorescence spectra and their temporal dynamics. The photophysical properties of plastic-embedded DPO are not substantially altered compared to those previously determined for this dye in solvents. Notably, the amount of delayed fluorescence is always greater than that of phosphorescence. However, our study of crystalline para-terphenyl suggests that a second phase called β (perhaps comprising more planar molecules) functions as a triplet trap and decreases the amount of delayed fluorescence relative to phosphorescence. While the "main form" of para-terphenyl dominates absorption, the emissive properties (fluorescence, phosphorescence, and delayed fluorescence) are dominated by the β-phase. Studies of the para-terphenyl crystal performed with femtosecond time-resolved transient absorption demonstrate that excitation from the main form of the para-terphenyl crystal is promptly transferred to the β-phase with a time constant of roughly 300 ps. This work provides insight into the photophysical properties of two scintillators utilized to differentiate γ-ray- and neutron-induced signals.

Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression.

Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD

) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype.

Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.

Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.