LANDING WITH A SUPINATED ANKLE JOINT COULD INCITE AN INVERSION SPRAIN INJURY

Ankle sprain injury mechanism has been recently analysed quantitatively. This study further investigated if a supinated ankle joint at landing is an aetiology of the injury. One inversion ankle sprain case from a previous study was selected, and the video sequences of two similar play movements performed by the same athlete without injury were collected and analysed by a model-based image-matching motion analysis method. The ankle joint orientations at the moment of landing in these three cases were compared. Results showed that the ankle joint was in a supination orientation with a combined 14 degrees inversion and 16 degrees plantarflexion at landing, while it was neutral in the inversion/eversion plane and dorsiflexed to 10-21 degrees in the non-injury cases. The supination ankle joint at landing was suggested to be the inciting event of the injury

Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment—twodimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSCderived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECMpromoted increased expression of calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC-derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment

Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized protooncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake

Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities

[[abstract]]Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual sodium channels remain to be studied. The role of zebrafish Nav1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown. MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Nav1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Nav1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Nav1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3 suggest that the function of Nav1.6 sodium channels is essential on the normal early embryonic locomotor activities.[[notice]]補正完畢[[journaltype]]國

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Preoperative predictors for residual tumor after surgery in patients with ovarian carcinoma

Objectives: Suboptimal debulking (>1 cm residual tumor) results in poor survival rates for patients with an advanced stage of ovarian cancer. The purpose of this study was to develop a prediction model, based on simple preoperative parameters, for patients with an advanced stage of ovarian cancer who are at risk of suboptimal cytoreduction despite maximal surgical effort. Methods: Retrospective analysis of 187 consecutive patients with a suspected clinical diagnosis of advanced-stage ovarian cancer undergoing upfront debulking between January 1998 and December 2003. Preoperative parameters were Karnofsky performance status, ascites and serum concentrations of CA 125, hemoglobin, albumin, LDH and blood platelets. The main outcome parameter was residual tumor >1 cm. Univariate and multivariate logistic regression was employed for testing possible prediction models. A clinically applicable graphic model (nomogram) for this prediction was to be developed. Results: Serum concentrations of CA 125 and blood platelets in the group with residual tumor >1 cm were higher in comparison to the optimally cytoreduced group (p 1 cm based on serum levels of CA 125 and albumin was established. Conclusion: Postoperative residual tumor despite maximal surgical effort can be predicted by preoperative CA 125 and serum albumin levels. With a nomogram based on these two parameters, probability of postoperative residual tumor in each individual patient can be predicted. This proposed nomogram may be valuable in daily routine practice for counseling and to select treatment modality. Copyrigh

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy