Combination Therapy with Immune Checkpoint Inhibitors and Histone Deacetylase Inhibitors or Alkylating Agents.

Purpose: Immune checkpoint inhibitors (CPIs) have been widely adopted in a number of early and advanced malignancies. Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) have been suggested to potentiate the actions of CPIs on tumor cells. We conducted a comprehensive literature review to explore the potential synergistic activity between CPIs, AAs, and HDACis. Patients and Methods: Clinical and non-clinical studies describing outcomes in patients with cancer receiving CPIs and either concomitant or sequential (pre- or post-CPI) AAs or HDACis were identified in PubMed using pre-defined search strings. Manual searches of key oncology congresses were similarly performed. All relevant articles and abstracts were manually screened for relevance, classified according to the specific anticancer agents used (CPIs, AAs, or HDACis), tumor entity, and whether treatment was concomitant or sequential. Results: Overall, 227 unique clinical studies across a range of tumor types, both solid tumors and hematological malignancies, were identified. One hundred and fifty-nine publications on Phase I and II clinical studies together with 41 publications on Phase III studies were examined. The most commonly investigated tumor types were melanoma, triple-negative breast cancer, non-small cell lung cancer, and Hodgkin lymphoma. The randomized clinical studies identified, all of which reported on the combination of a CPI with an AA, demonstrated superior outcomes in the combination arm compared with CPI or AA monotherapy. Similarly, combination therapy with CPIs and HDACis demonstrated promising activity. Conclusion: Sequential or concomitant administration of a CPI with an AA or an HDACi may improve outcomes for patients with a range of tumor types. There is a rationale to support further investigation into the potential for synergy between CPIs, alkylating agents and/or HDACis in both the non-clinical and clinical settings.

People being treated for cancer will often receive more than one drug at a time, and the concept of combining cancer drugs is frequently investigated as a potential opportunity to improve outcomes for patients. We reviewed the published literature for clinical trials and work undertaken in laboratories to explore whether combining targeted agents that stop cancer cells from multiplying (known as checkpoint inhibitors) with traditional chemotherapy that kills cancer cells could be a useful approach. We looked at evidence in publications where checkpoint inhibitors were used at the same time as chemotherapy, or given immediately before or after chemotherapy. The most important evidence came from clinical trials where outcomes for patients receiving combinations of treatment were directly compared with those from patients receiving a single treatment. These studies showed superior outcomes for patients who were treated with a combination of cancer drugs compared with patients receiving monotherapy. We also found evidence that adding another class of cancer drug, called histone deacetylase inhibitors, might sensitize tumors to checkpoint inhibitors. These findings provide a rationale for examining alkylating agents and/or histone deacetylase inhibitors combined with checkpoint inhibitors.

Exploring social media technologies for novice EFL school teachers to collaborate and communicate: A case in the Czech Republic.

With an increasing number of international schools, traditional EFL teaching methods may not satisfy students' needs. This study aims to investigate perceptions of social media technologies (e.g., Web 2.0) and willingness to adopt such technologies to collaborate and communicate in multicultural classrooms among novice EFL schoolteachers in the Czech Republic. The participants were 100 novice EFL schoolteachers in Prague and the South Moravian regions of the Czech Republic. The study used a mixed research method consisting of a survey (stage 1) and a semi-structured interview (stage 2). The survey examined the participants' appraisal and concerns of using social media technologies to collaborate and to communicate as well as the level of willingness to use social media technologies. A hierarchical cluster analysis using participants' responses regarding their attitudes and behavioural tendency towards using Web 2.0 social media technologies in language classrooms identified three clusters of teachers. The teachers who were most likely to adopt social Web 2.0 technologies were those who had the highest ratings on both appraisals and concerns regarding the use of social media in language classrooms. The results from the semi-structured interviews were consistent with those from the survey. Together, the results from the two stages demonstrated that most pre-service teachers favoured using Web 2.0 technology for collaboration and communication among colleagues and stakeholders in a broader community, but they displayed contrasting levels of appraisal of and concerns towards using social media technologies. Participants believed that this might be due to their different levels of ICT proficiency, workload, and working environment. The political and practical implications in K-12 education in the Czech context are also discussed.

The declining occurrence of moose (Alces alces) at the southernmost edge of its range raise conservation concerns.

The border region between Austria, the Czech Republic, and Germany harbors the most south-western occurrence of moose in continental Europe. The population originated in Poland, where moose survived, immigrated from former Soviet Union or were reintroduced after the Second World War expanded west- and southwards. In recent years, the distribution of the nonetheless small Central European population seems to have declined, necessitating an evaluation of its current status. In this study, existing datasets of moose observations from 1958 to 2019 collected in the three countries were combined to create a database totaling 771 records (observations and deaths). The database was then used to analyze the following: (a) changes in moose distribution, (b) the most important mortality factors, and (c) the availability of suitable habitat as determined using a maximum entropy approach. The results showed a progressive increase in the number of moose observations after 1958, with peaks in the 1990s and around 2010, followed by a relatively steep drop after 2013. Mortality within the moose population was mostly due to human interactions, including 13 deadly wildlife-vehicle collisions, particularly on minor roads, and four animals that were either legally culled or poached. Our habitat model suggested that higher altitudes (ca. 700-1,000 m a.s.l.), especially those offering wetlands, broad-leaved forests and natural grasslands, are the preferred habitats of moose whereas steep slopes and areas of human activity are avoided. The habitat model also revealed the availability of large core areas of suitable habitat beyond the current distribution, suggesting that habitat was not the limiting factor explaining the moose distribution in the study area. Our findings call for immediate transboundary conservation measures to sustain the moose population, such as those aimed at preventing wildlife-vehicle collisions and illegal killings. Infrastructure planning and development activities must take into account the habitat requirements of moose.