Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments

Purpose: Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. Methods: Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb’s method. The anatomy of the adjacent discs was observed histologically. Results: DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. Conclusions: Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.postprin

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Janus monolayers of transition metal dichalcogenides.

Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements

Bayesian Spatio-Temporal Modeling of Schistosoma japonicum Prevalence Data in the Absence of a Diagnostic ‘Gold’ Standard

Schistosomiasis is a serious public health problem in the People's Republic of China and elsewhere, and mapping of risk areas is important for guiding control interventions. Here, a 10-year surveillance database from Dangtu County in the southeastern part of the People's Republic of China was utilized for modeling the spatial and temporal distribution of infections in relation to environmental features and socioeconomic factors. Disease surveillance was done on the basis of a serological test, and we explicitly considered the imperfect sensitivity and specificity of the test when modeling the ‘true’ infection prevalence of Schistosoma japonicum. We then produced a risk map for S. japonicum transmission, which can assist decision making for local control interventions. Our work emphasizes the importance of accounting for the uncertainty in the diagnosis of schistosomiasis, and the potential of predicting the spatial and temporal distribution of the disease when using a Bayesian modeling framework. Our study can therefore serve as a template for future risk profiling of neglected tropical diseases studies, particularly when exploring spatial and temporal disease patterns in relation to environmental and socioeconomic factors, and how to account for the influence of diagnostic uncertainty

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Tools to Support Policy Decisions Related to Treatment Strategies and Surveillance of Schistosomiasis Japonica towards Elimination

Immunodiagnostic assays are widely applied in the field to control schistosomiasis in P.R. China as the prevalence and infection intensity of schistosome infections decrease. Field evaluations are urgently needed before they can be adopted to support policy decisions of the national programme for the control and elimination of schistosomiasis in P.R. China. We carried out a large scale cross-sectional survey in field settings with different transmission situations to validate immunodiagnostic tools that can be used to formulate new schistosomiasis elimination strategy in P.R. China. Regarding stool examination as gold reference, the validity and screening efficacy of each immunodiagnostic kit were calculated and compared with each other. The association of the prevalence of schistosomiasis and antibody positive rates determined by immunoassays were analyzed using Pearson's correlation coefficient values. The study indicates that which test to use with the elimination strategy is dependent on the purpose of testing, the endemic status of community and the resources available. And more sensitive methods need to be explored and used to target infected individuals for treatment or to eliminate schistosomiasis

ALMaQUEST. IV. The ALMA-MaNGA QUEnching and STar Formation (ALMaQUEST) Survey

The ALMaQUEST (ALMA-MaNGA QUEnching and STar formation) survey is a program with spatially-resolved $^{12}$CO(1-0) measurements obtained with the Atacama Large Millimeter Array (ALMA) for 46 galaxies selected from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) DR15 optical integral-field spectroscopic survey. The aim of the ALMaQUEST survey is to investigate the dependence of star formation activity on the cold molecular gas content at kpc scales in nearby galaxies. The sample consists of galaxies spanning a wide range in specific star formation rate (sSFR), including starburst (SB), main-sequence (MS), and green valley (GV) galaxies. In this paper, we present the sample selection and characteristics of the ALMA observations, and showcase some of the key results enabled by the combination of spatially-matched stellar populations and gas measurements. Considering the global (aperture-matched) stellar mass, molecular gas mass, and star formation rate of the sample, we find that the sSFR depends on both the star formation efficiency (SFE) and the molecular gas fraction ($f_{\rm H_{2}}$), although the correlation with the latter is slightly weaker. Furthermore, the dependence of sSFR on the molecular gas content (SFE or $f_{\rm H_{2}}$) is stronger than that on either the atomic gas fraction or the molecular-to-atomic gas fraction, albeit with the small HI sample size. On kpc scales, the variations in both SFE and $f_{\rm H_{2}}$ within individual galaxies can be as large as 1-2 dex thereby demonstrating that the availability of spatially-resolved observations is essential to understand the details of both star formation and quenching processes.STFC ER