Assessing the risk of vaccine-driven virulence evolution in SARS-CoV-2

The evolution of SARS-CoV-2 virulence, or lethality, threatens to exacerbate the burden of COVID-19 on society. How might COVID-19 vaccines alter selection for increased SARS-CoV-2 virulence? Framing current evidence surrounding SARS-CoV-2 biology and COVID-19 vaccines in the context of evolutionary theory indicates that prospects for virulence evolution remain uncertain. However, differential effects of vaccinal immunity on transmission and disease severity between respiratory compartments could select for increased virulence. To bound expectations for this outcome, we analyse an evo-epidemiological model. Synthesizing model predictions with vaccine efficacy data, we conclude that while vaccine-driven virulence remains a theoretical possibility, the risk is low if vaccines provide sustained robust protection against infection. Furthermore, we found that any increases in transmission concomitant with increases in virulence would be unlikely to threaten prospects for herd immunity in a highly immunized population. Given that virulence evolution would nevertheless impact unvaccinated individuals and populations with low vaccination rates, it is important to achieve high vaccination rates worldwide and ensure that vaccinal immunity provides robust protection against both infection and disease, potentially through the use of booster doses.

A review of the rational and current evidence on colchicine for COVID-19

: The current coronavirus disease (COVID-19) pandemic has affected about 247 million individuals around the world. Despite the extensive research efforts, there are currently few therapeutic options that offer direct clinical benefits for COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly high owing to the high viral transmission in several countries and the rise of various mutations in the SARS-CoV-2. One of the currently available and widely used drugs that combine both anti-inflammatory and immunomodulatory actions is colchicine, which has been proposed as a possible treatment option for COVID-19. Colchicine still did not get much attention from the medical and scientific communities despite its anti-inflammatory and immunomodulatory mechanisms of action and its positive preliminary data from early trials. This literature review article provides the scientific rationale for repurposing colchicine as a potential therapeutic of COVID-19. Further, we summarize its mechanisms of action and possible roles in COVID-19 patients. Finally, we supplement this review with a summary of the doses, side effects, and the early efficacy data from clinical trials to date. Despite the early promising findings from multiple observational and clinical trials about the potential of Colchicine in COVID-19, data from the RECOVERY trial, the largest COVID-19 RCT in the world, showed no evidence of clinical benefits in mortality, hospital stays, or disease progression (n=11340 patients). However, multiple other smaller clinical trials showed significant clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence. At the present, the drug should not be used except for investigational purposes.

Effect of perceived product innovativeness on consumers' product attribute preferences: The mediating role of self-efficacy

On the basis of the structural alignment model, we conducted two experiments to examine the effect of consumers' perceived product innovativeness on their product attribute preferences, and to test the mediating role of self-efficacy. Data were obtained from 263 participants, and the results showed that consumers paid more attention to alignable (vs. nonalignable) attributes when purchasing new products with low (vs. high) perceived innovativeness. Our results enrich previous findings on product innovativeness and the structural alignment model, and provide practical suggestions for enterprises to develop effective marketing strategies for new products.

An Embedded Multiscale Modelling to Guide Control and Elimination of Paratuberculosis in Ruminants

In recent years, multiscale modelling approach has begun to receive an overwhelming appreciation as an appropriate technique to characterize the complexity of infectious disease systems. In this study, we develop an embedded multiscale model of paratuberculosis in ruminants at host level that integrates the within-host scale and the between-host. A key feature of embedded multiscale models developed at host level of organization of an infectious disease system is that the within-host scale and the between-host scale influence each other in a reciprocal (i.e., both) way through superinfection, that is, through repeated infection before the host recovers from the initial infectious episode. This key feature is demonstrated in this study through a multiscale model of paratuberculosis in ruminants. The results of this study, through numerical analysis of the multiscale model, show that superinfection influences the dynamics of paratuberculosis only at the start of the infection, while the MAP bacteria replication continuously influences paratuberculosis dynamics throughout the infection until the host recovers from the initial infectious episode. This is largely because the replication of MAP bacteria at the within-host scale sustains the dynamics of paratuberculosis at this scale domain. We further use the embedded multiscale model developed in this study to evaluate the comparative effectiveness of paratuberculosis health interventions that influence the disease dynamics at different scales from efficacy data.

Place of CDK 4/6 and PARP inhibitors in the modern treatment approach of HER2-negative breast cancer

Three educational and discussion events with 35 key specialists from federal and regional cancer centers representing 7 federal districts were organized by Pfizer with the support of TS Oncology. The events were organized on the basis of the "OncoForum" platform (virtual platform developed and operated by TS Oncology). Experts shared their opinion on CDK4/6 inhibitors and PARP inhibitors place in the optimal therapy strategy for patients with HR+/HER2- metastatic breast cancer (mBC) and BRCA-associated HER2- mBC in Russia. This review presents results of the discussions on practical aspects of defining the optimal profiles of patients with HR+/HER2- mBC and BRCA-associated HER2- mBC for using CDK4/6 inhibitors and PARP inhibitors, evaluating the efficacy data and toxicity profiles for each of the CDK4/6 inhibitors and PARP inhibitors, as well as market access specifities for CDK4/6 inhibitors to patients with HR+/HER2- mBC and PARP inhibitors to patients with gBRCA-associated HER2- mBC in different regions of the Russian Federation.

Quantifying the level of Emotional intelligence and Self Efficacy

Considering the increasing no of universities, the present study was carried out to quantify the level of emotional intelligence and self efficacy. Data was collected via well-established questionnaire from 96 faculty members of both Public and private sector universities located in Khyber Pukhtoonkhwa. Results indicate the difference of emotional intelligence and self efficacy in both the sector.

NCOG-14. REAL-WORLD RETROSPECTIVE ANALYSIS OF TUMOR TREATING FIELDS IN THE TREATMENT OF HIGH-GRADE GLIOMA BASED ON CHINESE POPULATION

OBJECTIVES Tumor Treating Fields (TTFields) has been approved for the treatment of newly diagnosed and relapsed glioblastoma（GBM）in China in 2020. Only few TTFields data in Asia patients were reported. This retrospective analysis is aimed at investigating the efficacy, safety and the potential relationship with biomarkers of TTFields treatment in the real-world clinical practice of the Chinese glioma population. METHODS High-grade glioma patients who were under TTFields treatment from May 2019 to May 2021 in Shanghai Huashan Hospital were analyzed, including baseline data, efficacy data and incidence of adverse events. RESULTS Eighty-two patients (median age 51.0 [26.0 - 47.0] years) with high-grade glioma were enrolled, including 60 newly diagnosed GBM, 16 recurrent GBM, and 6 WHO grade III gliomas. The median time was 9.9 (4.6-15.7) months for follow-ups, median time for TTFields treatment was 4.3(1.1-20.35) months. The median compliance rate was 90% (40%-97%). For newly diagnosed GBM (n=60) and recurrent GBM (n=16), the 6-month PFS rate were 78.4% (95%CI: 63.9-87.6) and 46.7% (95%CI: 21.2- 67.8) respectively. The 10-month OS rate were 86.3% (95%CI: 69.6- 94.2) and 60.0% (95%CI: 12.6- 88.2) respectively. The 6-month PFS rate in the IDHw/TERTm population was 69.9% (95%CI: 45.9-84.9) and 78.3% (95%CI: 46.5-92.5) in the IDHw/TERTw patients with newly diagnosed GBM. 59(72%) patients had skin-related adverse reactions, and majority are grade 1-2 (grade 1-2, 69.5%; grade 3, 2.5%). CONCLUSIONS This is the 1st retrospective analysis done using TTFields in the treatment of high-grade gliomas in the Chinese population with the largest sample size. From our short follow up, TTFields appears good efficacy among GBM patients. The incidence of skin adverse reactions is higher comparable to published data, but mainly consisted of grade1-2. Long-term efficacy data need to be further followed-up.