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Conductivity and alignment of scaffolds are two primary factors influencing the efficacy of nerve repair. Herein, conductive composite fibers composed of poly(ɛ-caprolactone) (PCL) and carbon nanotubes (CNTs) with different orientation degrees are prepared by electrospinning at various rotational speeds (0, 500, 1000, and 2000 rpm), and meanwhile the synergistic promotion mechanism of aligned topography and electrical stimulation on neural regeneration is fully demonstrated. Under an optimized rotational speed of 1000 rpm, the electrospun PCL fiber exhibits orientated structure at macroscopic (mean deviation angle = 2.78°) or microscopic crystal scale (orientation degree = 0.73), decreased contact angle of 99.2° ± 4.9°, and sufficient tensile strength in both perpendicular and parallel directions to fiber axis (1.13 ± 0.15 and 5.06 ± 0.98 MPa). CNTs are introduced into the aligned fiber for further improving conductivity (15.69-178.63 S m-1 ), which is beneficial to the oriented growth of neural cells in vitro as well as the regeneration of injured sciatic nerves in vivo. On the basis of robust cell induction behavior, optimum sciatic nerve function index, and enhanced remyelination/axonal regeneration, such conductive PCL/CNTs composite fiber with optimized fiber alignment may serve as instructive candidates for promoting the scaffold- and cell-based strategies for neural repair.Germline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome, a cancer predisposition disorder inherited in an autosomal dominant pattern associated with a high risk of malignancy, including early-onset breast cancers, sarcomas, adrenocortical carcinomas, and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants is associated with reduced cancer-related mortality. Accurate and consistent classification of germline variants across clinical and research laboratories is important to ensure appropriate cancer surveillance recommendations. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were developed for 20 ACMG/AMP criteria, while nine were deemed not applicable. The original strength level for the 10 criteria was also adjusted due to current evidence. this website Use of TP53-specific guidelines and sharing of clinical data among experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% compared with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.Porous crystals with well-defined active metal centers on the pore surface have high potential as heterogeneous metal catalysts. We have recently demonstrated that a porous molecular crystal, metal-macrocycle framework (MMF), catalyzes olefin migration reactions by photoactivation of its PdII Cl2 moieties exposed on the crystalline channel surface. Herein we report a mechanistic study of the photoinduced olefin migration reactions at the PdII active centers of MMF. Several experiments, including a deuterium scrambling study, revealed that olefin migration is catalyzed via an alkyl mechanism by in situ generated Pd-H species on the channel surface during photoirradiation. This proposed mechanism was further supported by DFT and ONIOM calculations.Lung transplant referral guidelines for individuals with cystic fibrosis (CF) were published recently. Most of the recommendations focus on the specific indications and barriers to transplantation in adults with CF. Although the number of children with CF and end-stage lung disease continues to decrease, the specific issues related to pediatric patients merit further elucidation. We address each recommendation from the recent publication with a pediatric perspective. Furthermore, we note some significant differences between the practice and policy related to lung transplantation between Canada and the United States.Recent advances in 3D bioprinting allow for generating intricate structures with dimensions relevant for human tissue, but suitable bioinks for producing translationally relevant tissue with complex geometries remain unidentified. Here, a tissue-specific hybrid bioink is described, composed of a natural polymer, alginate, reinforced with extracellular matrix derived from decellularized tissue (rECM). rECM has rheological and gelation properties beneficial for 3D bioprinting while retaining biologically inductive properties supporting tissue maturation ex vivo and in vivo. These bioinks are shear thinning, resist cell sedimentation, improve viability of multiple cell types, and enhance mechanical stability in hydrogels derived from them. 3D printed constructs generated from rECM bioinks suppress the foreign body response, are pro-angiogenic and support recipient-derived de novo blood vessel formation across the entire graft thickness in a murine model of transplant immunosuppression. Their proof-of-principle for generating human tissue is demonstrated by 3D bioprinting human airways composed of regionally specified primary human airway epithelial progenitor and smooth muscle cells. Airway lumens remained patent with viable cells for one month in vitro with evidence of differentiation into mature epithelial cell types found in native human airways. rECM bioinks are a promising new approach for generating functional human tissue using 3D bioprinting.Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81-0.93], p less then .0001), similar graft survival, lower MELD at transplant (p less then .04), shorter waiting time (p less then .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p less then .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.Binary transition metal fluorides are textbook examples combining complex electronic features with most fundamental molecular structures. High-valent nickel fluorides are among the strongest known fluorinating and oxidizing agents, but there is a lack of experimental structural and spectroscopic investigations on molecular NiF3 or NiF4 . Apart from their demanding synthesis, also their quantum-chemical description is difficult due to their open shell nature and low-lying excited electronic states. Distorted tetrahedral NiF4 (D2d ) and trigonal planar NiF3 (D3h ) molecules were produced by thermal evaporation and laser ablation of nickel atoms in a fluorine/noble gas mixture and spectroscopically identified by a joint matrix-isolation and quantum-chemical study. Their vibrational band positions provide detailed insights into their molecular structures.Obstructive sleep apnea (OSA) may lead to increased circulating concentrations of inflammatory biomarkers and treatment may change these. We aimed to assess the effect of oral appliance (OA) therapy on inflammatory biomarkers in a randomised controlled pilot trial. A total of 71 patients with OSA and systemic hypertension were randomly allocated to an active, mandible protruded (OAa) or a passive, mandible non-protruded device (OAp) treatment. Serum concentrations of the inflammatory biomarkers white blood cells, high-sensitivity C-reactive protein, interleukin 6, interleukin 10, and tumour necrosis factor-α were measured at baseline and after 3 months of OA treatment. The differences between treatment groups in biomarker concentration change during the treatment were presented as the Vargha and Delaney effect size and evaluated with the Wilcoxon-Mann-Whitney test. This effect size expresses the probability of a higher value in a random participant from one group compared with a random patient from the other group, and a value of 0.5 means stochastically equal groups. link2 After 3 months of treatment, there was a significant reduction of the apnea-hypopnea index in the OAa group compared with the OAp group (effect size 0.258, 95% confidence interval 0.146-0.386, p less then .001). There were no significant differences between the groups in any of the inflammatory markers' concentration changes during the treatment period (effect sizes between 0.488 and 0.524; all p values ≥.737). Thus, OA treatment for 3 months did not affect circulating concentrations of some common inflammatory markers in patients with OSA and systemic hypertension.Cocaine-dependent (CD) individuals demonstrate significant anxiety and dysphoria during withdrawal, a negative emotional state that may perpetuate drug seeking and consumption. An extensive body of work has focused on characterizing reward circuit dysfunction, but relatively little is known about the pain circuit during cocaine withdrawal. In an earlier study, we highlighted how cue-elicited functional connectivity between the periaqueductal gray (PAG), a subcortical hub of the pain circuit, and ventromedial prefrontal cortex supports tonic craving in recently abstinent CD. The functional organization of the brain can be characterized by intrinsic connectivities, and it is highly likely that the resting state functional connectivity (rsFC) of the PAG may also be altered in association with cocaine use variables. Here, we examined this issue in 52 CD and 52 healthy control (HC) participants. Imaging data were processed with published routines, and the findings were evaluated with a corrected threshold. link3 In a covariance analysis, CD as compared with HC showed higher PAG rsFC with the hypothalamus, dorsomedial prefrontal, and inferior parietal cortices. Further, these connectivities were correlated negatively with tonic cocaine craving and recent cocaine use, respectively. Higher hypothalamic and frontoparietal rsFC with the PAG may reflect a compensatory process to regulate craving and compulsive drug use. The findings provide additional evidence in humans implicating the PAG circuit and may help research of the role of negative reinforcement in sustaining habitual drug use in cocaine addiction.

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