This is a case example on the concept of personalized precision medicine in a surgical setting and demonstrates how 3D-printed, patient-specific implants may bring individualized solutions to rare problems wherein restoration of the specific anatomy of each patient is a key prognostic factor.

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The recent finding that reprogrammed human pluripotent stem cells can be derived by nuclear transfer into human oocytes as well as by induced expression of defined factors has revitalized the debate on whether one approach might be advantageous over the other. Here we compare the genetic and epigenetic integrity of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal, and adult origin. The two cell types showed similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs had comparable numbers of de novo coding mutations, but significantly more than parthenogenetic ESCs. As iPSCs, NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of derivation approach.

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Phosphorylation is an important type of protein post-translational modification. Identification of possible phosphorylation sites of a protein is important for understanding its functions. Unbiased screening for phosphorylation sites by in vitro or in vivo experiments is time consuming and expensive; in silico prediction can provide functional candidates and help narrow down the experimental efforts. Most of the existing prediction algorithms take only the polypeptide sequence around the phosphorylation sites into consideration. However, protein phosphorylation is a very complex biological process in vivo. The polypeptide sequences around the potential sites are not sufficient to determine the phosphorylation status of those residues. In the current work, we integrated various data sources such as protein functional domains, protein subcellular location and protein-protein interactions, along with the polypeptide sequences to predict protein phosphorylation sites. The heterogeneous information significantly boosted the prediction accuracy for some kinase families. To demonstrate potential application of our method, we scanned a set of human proteins and predicted putative phosphorylation sites for Cyclin-dependent kinases, Casein kinase 2, Glycogen synthase kinase 3, Mitogen-activated protein kinases, protein kinase A, and protein kinase C families (avaiable at http://cmbi.bjmu.edu.cn/huphospho). The predicted phosphorylation sites can serve as candidates for further experimental validation. Our strategy may also be applicable for the in silico identification of other post-translational modification substrates.

Sustainable release of vancomycin from micro-arc oxidised 3D-printed porous Ti6A14V for treating MRSA bone infection and enhancing osteogenesis.

Background: Reconstruction following resection of the primary tumors of the upper cervical spine is challenging, and conventional internal implants develop complications in this region. 3D printing, also known as additive manufacturing, can produce patient-specific porous implants in a particular shape for bone defect reconstruction. This study aimed to describe the clinical outcomes of upper cervical spine reconstruction using customized 3D-printed vertebral body in 9 patients with primary tumors involving C2.Methods: Patients with primary tumors involving C2 who were treated in our institution between July 2014 and November 2018 were enrolled. A two-stage intralesional spondylectomy was performed using the posterior-anterior approach. Anterior reconstruction was accomplished using a customized 3D-printed vertebral body, which was fabricated by successive layering of melted titanium alloy powder using electron beam melting. No bone graft was used.Results: Nine patients (2 males and 7 females) were included in the study with a mean age of 31.4 years (12 to 59 years). Seven patients demonstrated tumors located in C2 and 2 showed involvement of C2 and C3. During a mean follow-up of 28.6 months (range, 12-42 months), 1 patient died of systemic metastasis and 1 had local tumor recurrence, the other 7 patients were alive and functional in their daily living until the last follow-up without evidence of disease. The 3D-printed vertebral bodies were all stable with no sign of displacement or subsidence, evidence of implant osseointegration was observed on the imaging studies. For the posterior instrumentation systems, no screw loosening or rod breakage was found.Conclusions: Spinal reconstruction in the upper cervical region using customized 3D-printed vertebral body is reliable. The tailored shape matching with the contact surfaces and the porous structure conductive to osseointegration provide both short-and long-term stability to the implant.

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