Network-based drug repurposing for HPV-associated cervical cancer.

In women, cervical cancer (CC) is the fourth most common cancer around the world with average cases of 604,000 and 342,000 deaths per year. Approximately 50% of high-grade CC are attributed to human papillomavirus (HPV) types 16 and 18. Chances of CC in HPV-positive patients are 6 times more than HPV-negative patients which demands timely and effective treatment. Repurposing of drugs is considered a viable approach to drug discovery which makes use of existing drugs, thus potentially reducing the time and costs associated with de-novo drug discovery. In this study, we present an integrative drug repurposing framework based on a systems biology-enabled network medicine platform. First, we built an HPV-induced CC protein interaction network named HPV2C following the CC signatures defined by the omics dataset, obtained from GEO database. Second, the drug target interaction (DTI) data obtained from DrugBank, and related databases was used to model the DTI network followed by drug target network proximity analysis of HPV-host associated key targets and DTIs in the human protein interactome. This analysis identified 142 potential anti-HPV repurposable drugs to target HPV induced CC pathways. Third, as per the literature survey 51 of the predicted drugs are already used for CC and 33 of the remaining drugs have anti-viral activity. Gene set enrichment analysis of potential drugs in drug-gene signatures and in HPV-induced CC-specific transcriptomic data in human cell lines additionally validated the predictions. Finally, 13 drug combinations were found using a network based on overlapping exposure. To summarize, the study provides effective network-based technique to quickly identify suitable repurposable drugs and drug combinations that target HPV-associated CC.

A Highly Sensitive and Flexible Capacitive Pressure Sensor Based on Alignment Airgap Dielectric.

Flexible capacitive pressure sensors with a simple structure and low power consumption are attracting attention, owing to their wide range of applications in wearable electronic devices. However, it is difficult to manufacture pressure sensors with high sensitivity, wide detection range, and low detection limits. We developed a highly sensitive and flexible capacitive pressure sensor based on the porous Ecoflex, which has an aligned airgap structure and can be manufactured by simply using a mold and a micro-needle. The existence of precisely aligned airgap structures significantly improved the sensor sensitivity compared to other dielectric structures without airgaps. The proposed capacitive pressure sensor with an alignment airgap structure supports a wide range of working pressures (20-100 kPa), quick response time (≈100 ms), high operational stability, and low-pressure detection limit (20 Pa). Moreover, we also studied the application of pulse wave monitoring in wearable sensors, exhibiting excellent performance in wearable devices that detect pulse waves before and after exercise. The proposed pressure sensor is applicable in electronic skin and wearable medical assistive devices owing to its excellent functional features.

Omni Directional Multimaterial Soft Cylindrical Actuator and Its Application as a Steerable Catheter.

Soft actuators with complex range of motion lead to strong interest in applying devices like biomedical catheters and steerable soft pipe inspectors. To facilitate the use of soft actuators in devices where controlled, complex, precise, and fast motion is required, a structurally controlled Omni directional soft cylindrical actuator is fabricated in a modular way using multilayer composite of polylactic acid based conductive Graphene, shape memory polymer, shape memory alloy, and polyurethane. Multiple fabrication techniques are discussed step by step that mainly include fused deposition modeling based 3D printing, dip coating, and UV curing. A mathematical control model is used to generate patterned electrical signals for the Omni directional deformations. Characterizations like structural control, bending, recovery, path, and thermal effect are carried out with and without load (10 g) to verify the new cylindrical design concept. Finally, the application of Omni directional actuator as a steerable catheter is explored by fabricating a scaled version of carotid artery through 3D printing using a semitransparent material.

A diagnostic algorithm to serologically differentiate West Nile virus from Japanese encephalitis virus infections and its validation in field surveillance of poultry and horses.

The detection of West Nile virus (WNV) in areas endemic for Japanese encephalitis virus (JEV) is complicated by the extensive serological cross-reactivity between the two viruses. A testing algorithm was developed and employed for the detection of anti-WNV antibody in areas endemic for JEV. Using this differentiation algorithm, a serological survey of poultry (2004 through 2009) and horses (2007 through 2009) was performed. Among 2681 poultry sera, 125 samples were interpreted as being positive for antibodies against JEV, and 14 were suspected to be positive for antibodies against undetermined flaviviruses other than WNV and JEV. Of the 2601 horse sera tested, a total of 1914 (73.6%) were positive to the initial screening test. Of these positive sera, 132 sera (5.1%) had been collected from horses that had been imported from the United States, where WNV is endemic. These horses had WNV vaccination records, and no significant pattern of increasing titer was observed in paired sera tests. Of the remaining 1782 positive sera 1468 sera (56.4%) were also found to contain anti-JEV antibodies, and were interpreted to be JEV-specific antibodies by the differentiation algorithm developed in this study. The remaining 314 horses (12.1%) for which a fourfold difference in neutralizing antibody titer could not be demonstrated, were determined to contain an antibody against an unknown (unidentified or undetermined) flavivirus. No evidence of WNV infections were found during the period of this study.

Serosurveillance for Japanese encephalitis, Akabane, and Aino viruses for Thoroughbred horses in Korea.

Recent global warming trends may have a significant impact on vector-borne viral diseases, possibly affecting vector population dynamics and disease transmission. This study measured levels of hemagglutination-inhibition (HI) antibodies against Japanese encephalitis virus (JEV) and neutralizing antibodies against Akabane virus (AKAV) and Aino virus (AINV) for Thoroughbred horses in Korea. Blood samples were collected from 989 racehorses in several provinces, between October 2005 and March 2007. Sera were tested using either an HI assay or a virus neutralization test. Approximately half (49.7%; 492/989) of the horses tested were antibody-positive for JEV. The HI titer against JEV was significantly correlated with racehorse age (p < 0.05). Horses with an HI antibody titer of 1 : 160 or higher accounted for 3.9% of the animals tested, indicating that vectors transmitting arthropod- borne viruses bit relatively few horses. In contrast, 3.8% (19/497) and 19.5% (97/497) of horse sera collected in March 2007 were positive against AKAV and AINV, respectively. The presence of antibodies against AKAV and AINV may indicate the multiplication of AKAV and AINV in these horses.

Factors concerning early embryonic death in thoroughbred mares in South Korea.

A total of 384 Thoroughbred mares were investigated to determine and evaluate the features of early embryonic death at nine equine farms on Jeju Island, South Korea, from 2001 to 2003. Overall, 771 matings for 384 mares resulted in 376 pregnancies 15 days after ovulation. Subsequently, 12.2% (46/376) of these early conceptuses were lost within 45 days after ovulation. Furthermore, about three quarters of the 46 embryonic deaths occurred between 16 and 25 days after ovulation. The incidence of embryonic death was highest in the barren (17.2%), more than 15 years old (15.4%), and more than 10 parities (18.2%) groups compared with the other groups (9.1-16.9%). Mares mated in March, April, and during the first estrus postpartum had higher embryonic death rates, (19.6%, 17.2%, and 24.6%, respectively). Mares with abnormal fluid and cysts in the uterus (18.0%) or multiple embryonic vesicles (23.1%) had higher embryonic death rates than those with normal uterine conditions (9.8%) or single embryonic vesicles (10.5%). The condition of mares, such as breeding condition and the environment of the embryo or fetus, are the major factors in relation to occurrence of early embryonic death.