Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation.

Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation.

A novel multi-view deep learning approach for BI-RADS and density assessment of mammograms.

Advanced deep learning (DL) algorithms may predict the patient's risk of developing breast cancer based on the Breast Imaging Reporting and Data System (BI-RADS) and density standards. Recent studies have suggested that the combination of multi-view analysis improved the overall breast exam classification. In this paper, we propose a novel multi-view DL approach for BI-RADS and density assessment of mammograms. The proposed approach first deploys deep convolutional networks for feature extraction on each view separately. The extracted features are then stacked and fed into a Light Gradient Boosting Machine (LightGBM) classifier to predict BI-RADS and density scores. We conduct extensive experiments on both the internal mammography dataset and the public dataset Digital Database for Screening Mammogra-phy (DDSM). The experimental results demonstrate that the proposed approach outperforms the single-view classification approach on two benchmark datasets by huge F1-score margins (+5% on the internal dataset and +10% on the DDSM dataset). These results highlight the vital role of combining multi-view information to improve the performance of breast cancer risk prediction.

Comparison of Submental Blood Collection with the Retroorbital and Submandibular Methods in Mice (Mus musculus).

Nonterminal blood sample collection of sufficient volume and quality for research is complicated in mice due to their small size and anatomy. Large (>100 µL) nonterminal volumes of unhemolyzed or unclotted blood currently are typically collected from the retroorbital sinus or submandibular plexus. We developed a third method-submental blood collection-which is similar in execution to the submandibular method but with minor changes in animal restraint and collection location. Compared with other techniques, submental collection is easier to perform due to the direct visibility of the target vessels, which are located in a sparsely furred region. Compared with the submandibular method, the submental method did not differ regarding weight change and clotting score but significantly decreased hemolysis and increased the overall number of high-quality samples. The submental method was performed with smaller lancets for the majority of the bleeds, yet resulted in fewer repeat collection attempts, fewer insufficient samples, and less extraneous blood loss and was qualitatively less traumatic. Compared with the retroorbital technique, the submental method was similar regarding weight change but decreased hemolysis, clotting, and the number of overall high-quality samples; however the retroorbital method resulted in significantly fewer incidents of insufficient sample collection. Extraneous blood loss was roughly equivalent between the submental and retroorbital methods. We conclude that the submental method is an acceptable venipuncture technique for obtaining large, nonterminal volumes of blood from mice.

Unexpected thrombocytopenia and anemia in cynomolgus monkeys induced by a therapeutic human monoclonal antibody.

Cynomolgus monkeys dosed with a therapeutic monoclonal antibody (mAbY.1) at ≥ 50 mg/kg had unexpected acute thrombocytopenia (nadir ~3,000 platelets/µl), sometimes with decreases in red cell mass. Increased activated macrophages, mitotic figures, and erythrophagocytosis were observed in the spleen. Binding of mAbY.1 to cynomolgus peripheral blood cells could not be detected in vitro. mAbY.1 induced phagocytosis of platelets by peripheral blood monocytes from cynomolgus monkeys, but not from humans. mAbs sharing the same constant domain (Fc) sequences, but differing from mAbY.1 in their variable domains, bound competitively to and had similar biological activity against the intended target. None of these antibodies had hematologic liabilities in vitro or in vivo. Neither the F(ab')2 portion of mAbY.1 nor the F(ab')2 portion on an aglycosylated Fc (IgG1) framework caused phagocytosis of platelets in vitro. These data suggest that the hematologic effects of mAbY.1 in cynomolgus monkeys likely occurred through an off-target mechanism, shown to be driven by 1 to 3 amino acid differences in the light chain. The hematologic effects made mAbY.1 an unsuitable candidate for further development as a therapeutic agent. This example demonstrates that nonclinical safety studies may be essential for understanding off-target effects of mAbs prior to clinical trials.

Differential inhibitory effects of carbon tetrachloride on the hepatic plasma membrane, mitochondrial and endoplasmic reticular calcium transport systems: implications to hepatotoxicity.

Mitochondrial, endoplasmic reticular and plasma membrane fractions were isolated by a new method from control male Fischer 344 rats and rats given CCl4 by gavage. After 1 h of CCl4 treatment, rats were in glucose and pancreatic hormone balance but plasma levels of T3 and T4 were decreased 29 and 22%, respectively. After 24 hours of CCl4 treatment, rats were: hypoglycaemic and insulin and glucagon levels were increased 33- and 35-fold, respectively; total T4 levels were decreased 62%; while total T3 levels were normalized. In liver fractions from CCl4-treated rats, 1 h after CCl4 administration: (i) calcium binding was decreased 65% in the mitochondrial fraction, 66% in the endoplasmic reticular fraction and 46% in the plasma membrane fraction; (ii) calcium uptake was decreased 59% in the mitochondrial fraction, 46% in the endoplasmic reticular fraction and 37% in the plasma membrane fraction. After 24 h of CCl4 administration: (i) calcium binding was decreased 57% in the mitochondrial fraction, 50% in the endoplasmic reticular fraction and 71% in the plasma membrane fraction; (ii). calcium uptake was decreased 55% in the mitochondrial fraction, 17% in the endoplasmic reticular fraction and 53% in the plasma membrane fraction. In vitro studies indicated the plasma membrane calcium transport system to be rapidly (within a minute) and strongly (>90%) inhibited by CCl4. We conclude that CCl4 produces a differential inhibitory effect on the hepatocyte calcium pumps that are implicated with hepatocellular damage.