Academic tweeting in #ObGyn. Where do we stand?

Objective To describe the scenario of academic tweeting and utilization of Twitter by editorial board members of the leading journal in obstetrics and gynecology. Methods The Twitter presence of an editorial board members of obstetrics and gynecology journal with an impact factor greater than 4 was determined. Details of their Twitter activity, year of graduation from medical school and gender were analyzed. Median SparkScore™, an online influence measure, of journals was compared to the highest impact factor journals in medicine (New England Journal of Medicine, The Lancet, The British Medical Journal and Journal of the American Medical Association). Results In the six highest impact factor journals in obstetrics and gynecology, 92 of 240 (38.3%) editorial board members had an active Twitter account. The Twitter presence of editorial members of Obstetrics and Gynecology was statistically less when compared to all other journals (P < 0.01). The median number of tweets in the last 24 h and 7 days were 0. Median SparkScore™ for the highest impact factor obstetrics and gynecology journals (24) were lower compared to the highest impact journals in medicine (66) (P = 0.03). Conclusion Editorial board members of the six highest impact factor journals in obstetrics and gynecology are not capitalizing on the dynamic nature of Twitter and its instant convenient access from our smartphones to further academia, when compared to specialties in medicine. There is a need for increased adoption of Twitter among physician leaders in the specialty.

Updated Review and Perspective on 20S Proteasome Inhibitors in the Treatment of Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Most lung cancer patients are diagnosed at advanced stages and may benefit from pembrolizumab (anti-PD-1 antibody), cytotoxic chemotherapy and other adjuvant therapies. Despite the availability of various therapies, the response and survival rates have been low. Therefore, the study of different targets for the treatment of lung cancer has been one of the major focuses of cancer research. The ubiquitin proteasome system (UPS) is a crucial regulator of cell homeostasis and plays an essential role in the growth and development of all cells. The UPS is dysregulated in human cancer cells including lung cancer cells. Therefore, targeting UPS is potentially a selective, effective treatment for lung cancer. Bortezomib, a 20S proteasome inhibitor that is clinically approved for the management of multiple myeloma, has been studied in various preclinical and clinical models of lung cancer. Most preclinical studies have shown that a 20S proteasome inhibitor alone and its combination with other chemotherapeutic agents induce apoptosis in non-small cell lung cancer cell lines and animal models. Owing to the impressive preclinical results, many clinical trials were initiated using 20S proteasome inhibitors either as monotherapy or in combination with other conventional lung cancer therapies. Many combinational therapies of 20S PIs with conventional chemotherapy were shown to be well tolerated in clinical trials. However, there have not been any consistent data showing the beneficial effects of such proteasome inhibitor-based therapies. Low clinical efficacy of 20S PIs in lung cancer patients may be due to low drug penetration, the status of 20S proteasomes, oncogene expressions and the inherited or acquired resistance. Potential mechanisms of PI resistance or low or no clinical activity in lung cancer cells might include alteration of apoptotic proteins, overexpression or alteration of ß5 subunit, or upregulation of heat shock proteins. Various cutting-edge strategies to counter this resistance or improve 20S PIs' efficacy in lung cancer cells have been reviewed which include novel combination therapies, new drug delivery systems, development of more potent PIs, and targeting different sites of the UPS. A better understanding of PI resistance mechanisms in lung cancer cells can help improve current clinical treatment strategies and clinical outcomes.

Small molecules as antagonists of co-inhibitory pathways for cancer immunotherapy: a patent review (2018-2019).

INTRODUCTION: Therapeutic antibodies blocking co-inhibitory pathways do not attack tumor cells directly, but instead bind to their targeted proteins and mobilize the immune system to eradicate tumors. However, only a small fraction of patients with certain cancer types can benefit from the antibodies. Additionally, antibodies have shown serious immune-related adverse events in certain patients. Small-molecule antagonists may be a complementary and potentially synergistic approach to antibodies for patients with various cancers. AREAS COVERED: The authors review the small molecules as antagonists of co-inhibitory pathway proteins, summarize their preliminary SARs, discuss biochemistry assays used in patents for the development of small molecules as novel antagonists. EXPERT OPINION: The disclosed pharmacophores of small molecules as co-inhibitory pathway antagonists are represented by biphenyl derivatives, biaryl derivatives, teraryl derivatives, quateraryl derivatives, and oxadiazole/thiadiazole derivatives. However, these antagonists are still inferior to therapeutic antibodies in their inhibitory activities due to relatively flat of human co-inhibitory pathways proteins. Allosteric modulators may be an alternative approach. The more safety and efficacy evaluation trials of small-molecule antagonists targeting co-inhibitory pathways should be performed to demonstrate the proof-of-principle that small-molecule antagonists can result in sustained safety and antitumor response in the near future.