Deep learning models have achieved high performance on many tasks, and thus have been applied to many security-critical scenarios. For example, deep learning-based face recognition systems have been used to authenticate users to access many security-sensitive applications like payment apps. Such usages of deep learning systems provide the adversaries with sufficient incentives to perform attacks against these systems for their adversarial purposes.

Background/Aims: The overexpression of ATP-Binding Cassette (ABC) transporters has known to be one of the major obstacles impeding the success of chemotherapy in drug resistant cancers. In this study, we evaluated voruciclib, a CDK 4/6 inhibitor, for its chemo-sensitizing activity in ABCB1- and ABCG2- overexpressing cells. Methods: Cytotoxicity and reversal effect of voruciclib was determined by MTT assay. The intracellular accumulation and efflux of ABCB1 and ABCG2 substrates were measured by scintillation counter. The effects on expression and intracellular localization of ABCB1 and ABCG2 proteins were determined by Western blotting and immunofluorescence, respectively. Vanadate-sensitive ATPase assay was done to determine the effect of voruciclib on the ATPase activity of ABCB1 and ABCG2. Flow cytometric analysis was done to determine the effect of voruciclib on apoptosis of ABCB1 and ABCG2-overexpressing cells and docking analysis was done to determine the interaction of voruciclib with ABCB1 and ACBG2 protein. Results: Voruciclib significantly potentiated the effect of paclitaxel and doxorubicin in ABCB1-overexpressing cells, as well as mitoxantrone and SN-38 in ABCG2-overexpressing cells. Voruciclib moderately sensitized ABCC10- overexpressing cells to paclitaxel, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, voruciclib increased the intracellular accumulation and decreased the efflux of substrate anti-cancer drugs from ABCB1- or ABCG2-overexpressing cells. However, voruciclib did not alter the expression or the sub-cellular localization of ABCB1 or ABCG2. Voruciclib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner. Lastly, voruciclib exhibited a drug-induced apoptotic effect in ABCB1- or ABCG2- overexpressing cells. Conclusion: Voruciclib is currently a phase I clinical trial drug. Our findings strongly support its potential use in combination with conventional anti-cancer drugs for cancer chemotherapy.

ObjectiveCurrent anticonvulsant screening programs are based on seizures evoked in normal animals. One‐third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high‐throughput in vitro models to low‐throughput in vivo models.MethodsEpileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure‐like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings.ResultsWe screened 407 compound‐concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy.InterpretationThe use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure‐like activity and seizure‐induced cell death can be easily quantified with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to find an anticonvulsant that would be missed by screening in acute models.

Short- and long-term readmission rates in a safety net setting are high. The 30-day rates in this study are higher than historically reported. This data sets baseline rates for 90-day and 1-year readmission for future analyses. Although the majority of short-term readmissions are related to the index procedure, long-term readmission rates are more frequently related to systemic comorbidities. Targeted patient interventions aimed at preventing the most common reasons for readmission may improve readmission rates, particularly among patients with nonprivate insurance. However, other risk factors, such as tibial target, may not be modifiable and a higher readmission rate may need to be accepted in this population.

While topotecan (TPT) is a first- and second-line chemotherapeutic drug in treating lung cancer, the development of drug resistance in tumors still reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of topotecan resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in topotecan-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143. The NCI-H460/TPT10 cell line and its parental cell line can be useful for drug screening and developing targeted strategies to overcome ABCG2-mediated MDR in NSCLC.

A text simplification system is developed that accepts as input a document written for college reading level, and converts it to high school reading level text using techniques in natural language processing. The achieved level of lexical and syntactic simplifications is dependent on the lexical and syntactic information stored in the system's knowledge sources. These knowledge sources can be updated when necessary, thus allowing the system to support varying input and output reading levels. Test results show that simplification can increase the reading ease score from as low as 2.5% to as high as 296%. Results also show that only 70% of the generated easier-to-read text will have a reading ease score higher than the original input sentence.

Infrainguinal arterial occlusive disease can lead to potentially disabling and limb-threatening conditions. Revascularization may be indicated for claudication, rest pain, or tissue loss. Although endovascular interventions are becoming more prevalent, open surgeries such as endarterectomy and bypass are still needed and performed regularly. Open reconstruction has been associated with postoperative morbidity, both at the local and at the systemic levels. Local complications include surgical site infections (SSIs 0–5.3%), graft failure (12–60%), and amputation (5.7–27%), and more systemic issues include cardiac (2.6–18.4%), respiratory (2.5%), renal (4%), neurovascular (1.5%), and thromboembolic (0.2–1%) complications. While such outcomes present an additional challenge to the postoperative management of surgical patients, it may be possible to minimize their occurrence through careful risk stratification and preoperative assessment. Therefore, individualized selection of candidates for open repair requires weighing the need for intervention against the likelihood of adverse outcomes based on preoperative risk factors. This review provides an overview of open reconstruction, focusing on identifying the clinical indications for surgery and perioperative morbidity and mortality.

In the Vascular Quality Initiative, as ambulatory status declines, perioperative morbidity and mortality increase. Impaired ambulatory patients are more likely to receive PVI than LEB for the treatment of CLI, although even among nonambulatory patients, there are still a significant number who receive LEB.