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Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENT Astrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.

When receiving machine learning services from the cloud, the provider doesnot need to receive all features; in fact, only a subset of the features arenecessary for the target prediction task. Discerning this subset is the keyproblem of this work. We formulate this problem as a gradient-basedperturbation maximization method that discovers this subset in the inputfeature space with respect to the functionality of the prediction model used bythe provider. After identifying the subset, our framework, Cloak, suppressesthe rest of the features using utility-preserving constant values that arediscovered through a separate gradient-based optimization process. We show thatCloak does not necessarily require collaboration from the service providerbeyond its normal service, and can be applied in scenarios where we only haveblack-box access to the service provider's model. We theoretically guaranteethat Cloak's optimizations reduce the upper bound of the Mutual Information(MI) between the data and the sifted representations that are sent out.Experimental results show that Cloak reduces the mutual information between theinput and the sifted representations by 85.01% with only a negligible reductionin utility (1.42%). In addition, we show that Cloak greatly diminishesadversaries' ability to learn and infer non-conducive features.

A wide variety of deep neural applications increasingly rely on the cloud toperform their compute-heavy inference. This common practice requires sendingprivate and privileged data over the network to remote servers, exposing it tothe service provider and potentially compromising its privacy. Even if theprovider is trusted, the data can still be vulnerable over communicationchannels or via side-channel attacks in the cloud. To that end, this paper aimsto reduce the information content of the communicated data with as little aspossible compromise on the inference accuracy by making the sent data noisy. Anundisciplined addition of noise can significantly reduce the accuracy ofinference, rendering the service unusable. To address this challenge, thispaper devises Shredder, an end-to-end framework, that, without altering thetopology or the weights of a pre-trained network, learns additive noisedistributions that significantly reduce the information content of communicateddata while maintaining the inference accuracy. The key idea is finding theadditive noise distributions by casting it as a disjoint offline learningprocess with a loss function that strikes a balance between accuracy andinformation degradation. The loss function also exposes a knob for adisciplined and controlled asymmetric trade-off between privacy and accuracy.Experimentation with six real-world DNNs from text processing and imageclassification shows that Shredder reduces the mutual information between theinput and the communicated data to the cloud by 74.70% compared to the originalexecution while only sacrificing 1.58% loss in accuracy. On average, Shredderalso offers a speedup of 1.79x over Wi-Fi and 2.17x over LTE compared tocloud-only execution when using an off-the-shelf mobile GPU (Tegra X2) on theedge.

Objective Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair. Methods The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined. Results Three hundred and thirty-four (334) cases were included. Intraoperative CSF leak was encountered in 116 cases (34.7%), and postoperative CSF leak occurred only once (0.3%) early in the series. Seventy intraoperative CSF leaks were successfully repaired with an epidural interlay alone, including 13 high-flow leaks. Our rate of fat graft use (1.2%), nasoseptal flap (3.0%), and lumbar drain placement (6.6%) in the second half of the series showed a significant decline compared with the first half, indicating increased reliance on the interlay graft over time. Our 65% functional macroadenoma remission rate compares favorably with large historical series. Conclusion Simple sellar repair using an epidural interlay graft is highly effective in preventing postoperative CSF leaks, including cases of high-flow intraoperative leaks. More complex repair techniques are reserved for select high-risk cases or those with inadequate sellar bony ledges. With this technique, there has been no postoperative CSF leak at our institution in over 300 consecutive transsphenoidal pituitary surgeries. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of zoledronic acid (ZA) and antibacterial CM11 peptide on the osteoinduction and antibacterial properties of bioactive glass (BG). The bioactive glass/gelatin (BG/Gel) composite was synthesized using the sol-gel method. The 2-x minimum inhibitory concentration of the peptide and 4.00 mg mL-1 of ZA were added to the BG/Gel during fabrication. The BG/Gel composite morphological and structural characteristics and antibacterial activities were analyzed using Fourier transform infra-red spectroscopy, scanning electron microscopy and disk diffusion test, respectively. The release of the peptide and ZA from BG/Gel was measured using ultra-violet spectroscopy. After 14 days, the effects of the peptide/ZA-containing BG/Gel (PZ-BG/Gel) on the growth and differentiation of mesenchymal stem cells were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide, calcium and alkaline phosphatase assays, immunocytochemical staining for osteocalcin (OCN) and realtime polymerase chain reaction for OCN, type I collagen, bone morphogenetic protein 2 and Runtrelated transcription factor-2 genes. The disk diffusion test showed the anti-microbial activity of the scaffold against multi-drug-resistant isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Analyses showed a significantly higher level of stem cells differentiation into the osteogenic cells in PZ-BG/Gel scaffold compared to BG/Gel scaffold alone. Accordingly, osteoblast markers were significantly increased in comparison with the control. In conclusion, the osteoinduction and antibacterial properties of BG-based scaffold can be improved using ZA and CM11. [ABSTRACT FROM AUTHOR]