Biomechanical evaluation of three surgical scenarios of posterior lumbar interbody fusion by finite element analysis

BACKGROUND: For the treatment of low back pain, the following three scenarios of posterior lumbar interbody fusion (PLIF) were usually used, i.e., PLIF procedure with autogenous iliac bone (PAIB model), PLIF with cages made of PEEK (PCP model) or titanium (Ti) (PCT model) materiel. But the benefits or adverse effects among the three surgical scenarios were still not fully understood. METHOD: Finite element analysis (FEA), as an efficient tool for the analysis of lumbar diseases, was used to establish a three-dimensional nonlinear L1-S1 FE model (intact model) with the ligaments of solid elements. Then it was modified to simulate the three scenarios of PLIF. 10 Nm moments with 400 N preload were applied to the upper L1 vertebral body under the loading conditions of extension, flexion, lateral bending and torsion, respectively. RESULTS: Different mechanical parameters were calculated to evaluate the differences among the three surgical models. The lowest stresses on the bone grafts and the greatest stresses on endplate were found in the PCT model. The PCP model obtained considerable stresses on the bone grafts and less stresses on ligaments. But the changes of stresses on the adjacent discs and endplate were minimal in the PAIB model. CONCLUSIONS: The PCT model was inferior to the other two models. Both the PCP and PAIB models had their own relative merits. The findings provide theoretical basis for the choice of a suitable surgical scenario for different patients

The relationship between BSP mRNA expression and 25(OH)D/OPG in peripheral blood of newly diagnosed T2DM patients with different bone mass

Introduction: The objective of the study was to detect the levels of osteoprotegerin (OPG) and 25-hydroxyvitamin D [25(OH)D], as well as the expression of bone sialoprotein (BSP) mRNA, in the peripheral blood of patients with newly diagnosed type 2 diabetes mellitus (T2DM) under different bone mass conditions, and to explore its role and significance in the development process of T2DM combined with osteoporosis (OP). Material and methods: A total of 225 patients hospitalised in the Endocrinology Department and General Department from May 2017 to May 2018 were enrolled and categorised into five groups: the pure T2DM group (group A, 45 patients), the bone mass reduction group (group B, 45 patients), the T2DM + bone mass reduction group (group C, 45 patients), the OP group (group D, 45 patients), and the T2DM + OP group (group E, 45 patients); meanwhile, age-matched healthy subjects undergoing physical examination in our hospital were collected as the normal control group (group NC, 45 cases). Logistic regression analysis was used to analyse the influencing factors of bone mass in patients with T2DM. Results: Compared with group B, the expression levels of glycated haemoglobin (HbA1c), 25(OH)D, N-terminal propeptide of type I procollagen (PINP), fasting plasma glucose (FPG), fasting plasma insulin (FINS), high-density lipoprotein cholesterol (HDL-C), and BSP mRNA were significantly increased while OPG and b-collagen degradation products (b-CTX) were significantly decreased in group A. Conclusion: The expression of BSP mRNA and the decrease of 25(OH)D and OPG in peripheral blood may participate in the development of diabetes and osteoporosis

A Single {frame}

1 volume, 6 pages. Numbered edition of 12 copies. printed in Caslon Old Style on French paper with watercolor and lino-cuts --colophon. .. [Produced] spring 2019 [for] Art 136: The Artist\u27s Book course, taught by Tia Blassingame --colophon. Combines handset letterpress, linocuts, watercolor, papercutting and an interactive element to express the significance of self. --Scripts Press.https://digitalcommons.risd.edu/specialcollections_artistsbooks/1194/thumbnail.jp

The Janus Interface: How Fine-Tuning in Large Language Models Amplifies the Privacy Risks

The era post-2018 marked the advent of Large Language Models (LLMs), with innovations such as OpenAI's ChatGPT showcasing prodigious linguistic prowess. As the industry galloped toward augmenting model parameters and capitalizing on vast swaths of human language data, security and privacy challenges also emerged. Foremost among these is the potential inadvertent accrual of Personal Identifiable Information (PII) during web-based data acquisition, posing risks of unintended PII disclosure. While strategies like RLHF during training and Catastrophic Forgetting have been marshaled to control the risk of privacy infringements, recent advancements in LLMs, epitomized by OpenAI's fine-tuning interface for GPT-3.5, have reignited concerns. One may ask: can the fine-tuning of LLMs precipitate the leakage of personal information embedded within training datasets? This paper reports the first endeavor to seek the answer to the question, particularly our discovery of a new LLM exploitation avenue, called the Janus attack. In the attack, one can construct a PII association task, whereby an LLM is fine-tuned using a minuscule PII dataset, to potentially reinstate and reveal concealed PIIs. Our findings indicate that, with a trivial fine-tuning outlay, LLMs such as GPT-3.5 can transition from being impermeable to PII extraction to a state where they divulge a substantial proportion of concealed PII. This research, through its deep dive into the Janus attack vector, underscores the imperative of navigating the intricate interplay between LLM utility and privacy preservation

Exosomal cell-to-cell transmission of alpha synuclein oligomers

Background: Aggregation of alpha-synuclein (αsyn) and resulting cytotoxicity is a hallmark of sporadic and familial Parkinson’s disease (PD) as well as dementia with Lewy bodies, with recent evidence implicating oligomeric and pre-fibrillar forms of αsyn as the pathogenic species. Recent in vitro studies support the idea of transcellular spread of extracellular, secreted αsyn across membranes. The aim of this study is to characterize the transcellular spread of αsyn oligomers and determine their extracellular location. Results: Using a novel protein fragment complementation assay where αsyn is fused to non-bioluminescent amino-or carboxy-terminus fragments of humanized Gaussia Luciferase we demonstrate here that αsyn oligomers can be found in at least two extracellular fractions: either associated with exosomes or free. Exosome-associated αsyn oligomers are more likely to be taken up by recipient cells and can induce more toxicity compared to free αsyn oligomers. Specifically, we determine that αsyn oligomers are present on both the outside as well as inside of exosomes. Notably, the pathway of secretion of αsyn oligomers is strongly influenced by autophagic activity. Conclusions: Our data suggest that αsyn may be secreted via different secretory pathways. We hypothesize that exosome-mediated release of αsyn oligomers is a mechanism whereby cells clear toxic αsyn oligomers when autophagic mechanisms fail to be sufficient. Preventing the early events in αsyn exosomal release and uptake by inducing autophagy may be a novel approach to halt disease spreading in PD and other synucleinopathies

Direct detection of alpha synuclein oligomers in vivo

Background: Rat models of Parkinson’s disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo. Results: Viral coinjection resulted in widespread VenusYFP signal within the nigrostriatal pathway, including cell bodies in the substantia nigra and synaptic accumulation in striatal terminals, suggestive of in vivo alpha-synuclein oligomers formation. Transduced rats showed alpha-synuclein induced dopaminergic neuron loss in the substantia nigra, the appearance of dystrophic neurites, and gliosis in the striatum. Moreover, we have applied in vivo imaging techniques in the living mouse to directly image alpha-synuclein oligomers in the cortex. Conclusion: We have developed a unique animal model that provides a tool for the Parkinson’s disease research community with which to directly detect alpha- synuclein oligomers in vivo and screen therapeutic approaches targeting alpha-synuclein oligomers

Identification and Characterization of \u3cem\u3eOGG1\u3c/em\u3e Mutations in Patients with Alzheimer\u27s Disease

Patients with Alzheimer\u27s disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no alterations were detected in any control samples, four AD patients exhibited mutations in OGG1, two carried a common single base (C796) deletion that alters the carboxyl terminal sequence of OGG1, and the other two had nucleotide alterations leading to single amino acid substitutions. In vitro biochemical assays revealed that the protein encoded by the C796-deleted OGG1 completely lost its 8-oxoG glycosylase activity, and that the two single residue-substituted OGG1 proteins showed a significant reduction in the glycosylase activity. These results were consistent with the fact that nuclear extracts derived from a limited number of AD patients with OGG1 mutations exhibited greatly reduced 8-oxoG glycosylase activity compared with age-matched controls and AD patients without OGG1 alterations. Our findings suggest that defects in OGG1 may be important in the pathogenesis of AD in a significant fraction of AD patients and provide new insight into the molecular basis for the disease

Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing

Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method—multiple annealing and looping-based amplification cycles—to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.Chemistry and Chemical Biolog

Sterically Induced Binding Selectivity of Single m-Terphenyl Isocyanide Ligands

Sterically encumbering m-terphenyl isocyanides are a class of metal-binding group that foster low-coordinate metal-center environments in coordination chemistry by exerting considerable intermolecular steric pressures between neighboring ligands. In the context of metal surfaces, the encumbering steric properties of the m-terphenyl isocyanides are shown to weaken the interaction between the metal-binding group and a planar substrate, leading to a preference for molecular adsorption at sites with convex curvature, such as the step edges and herringbone elbow sites on Au(111). Here, we investigate the site-selective binding of individual m-terphenyl isocyanide ligands on a Au(111) surface through scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy (IETS). The site-dependent steric pressure alters the vibrational fingerprint of the m-terphenyl isocyanides, which is characterized with single-molecule precision through joint experimental and theoretical approaches. This study for the first time provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual m-terphenyl isocyanide ligands, thereby highlighting the potential to control the physical and chemical properties of metal surfaces through tailored ligand design