Livelihood challenges and healthcare-seeking behavior of fishermen amidst the COVID-19 pandemic in the Sundarbans mangrove forest of Bangladesh.

The outbreak of coronavirus disease (COVID-19) has posed significant challenges to human wellbeing and survival, particularly among groups of people such as the Sundarbans mangrove forest resource-dependent communities (SMFRDCs), and especially the fishermen in these communities, in developing countries like Bangladesh. It is therefore essential to explore the livelihood conditions, health status and care-seeking behavior of the fishermen in these communities during the ongoing pandemic. This study was carried out by applying mixed methods, including interviews and focus group discussion (FGD), in the three sub-districts of Khulna, Satkhira, and Bagerhat, which are in the southwestern region adjacent to the Sundarbans mangrove forest (SMF) of Bangladesh. Quantitative data were collected from 76 fishermen through telephone interviews, while 24 fishermen participated in three distinct focus group discussions. The findings suggest that the fishermen have experienced a reduction of income, as they have been barred from entering the SMF during the pandemic, which has gradually affected their number of trips to and stays at the forest as well as their catch of fisheries resources. The decline in demand in both regional and international markets has left the fishermen with only a handful of alternative ways to adjust to these unprecedented circumstances, such as borrowing money, selling household assets, and in some extreme cases marrying off young children to reduce the financial burden, as many are now jobless. Their financial hardship during the pandemic has affected their households' capacity to afford basic household necessities, including food, fuel, education, and health expenses. Subsequently, when these fishermen suffer ailments such as fever, cough, headache, and cold - the general symptoms of COVID-19 - they cannot seek medical assistance from trained doctors. Their financial constraints have compelled them to rely on indigenous knowledge, in particular village quack doctors, or in some cases to seek help from local pharmacies for modern medicine. Thus, the government should provide financial support and strengthen the local market value chain so that disadvantaged fishermen in SMFRDCs can adopt alternative livelihood opportunities. Furthermore, longitudinal research on the impacts of COVID-19 on livelihood, local adaptation strategies, health status, and care-seeking behavior is also strongly recommended.

Prolonged lockdown and academic uncertainties in Bangladesh: A qualitative investigation during the COVID-19 pandemic.

The erratic nature of the novel coronavirus disease (COVID-19) forced the Bangladeshi government to shut down all the educational institutions since March 18, 2020. This prolonged closure not only detached the students from their study but also increased anxiety among them regarding their future academic as well as professional careers. The present study aimed to explore the perception and understanding of the students and teachers regarding the impact of COVID-19 on the academic life and career pursuit of university students in Bangladesh. With a semi-structured interview schedule, data for this qualitative study were collected from 8 purposively selected participants, using telephone interviews, affiliated with a public university in Bangladesh. Students argued that the extended closure is responsible for the delayed graduation of the senior students, thereby, mounting mental stress and frustration among them. The informants unequivocally opposed the online education platform, as a solution for the ongoing gap, due to scarcity of the resources, and unequal accesses and opportunities for all. It has been suggested that the education gap can be reduced by shortening the term, curtailing the preparatory leave, and taking extra classes over the weekends when the universities re-open together with enforced collective health hygiene.

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.

Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.

TGF-ß-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure.

The extracellular matrix (ECM) is a key determinant of cancer progression and prognosis. Here we report findings from one of the largest pan-cancer analyses of ECM gene dysregulation in cancer. We define a distinct set of ECM genes upregulated in cancer (C-ECM) and linked to worse prognosis. We found that the C-ECM transcriptional programme dysregulation is correlated with the activation of TGF-ß signalling in cancer-associated fibroblasts and is linked to immunosuppression in otherwise immunologically active tumours. Cancers that activate this programme carry distinct genomic profiles, such as BRAF, SMAD4 and TP53 mutations and MYC amplification. Finally, we show that this signature is a predictor of the failure of PD-1 blockade and outperforms previously-proposed biomarkers. Thus, our findings identify a distinct transcriptional pattern of ECM genes in operation across cancers that may be potentially targeted, pending preclinical validation, using TGF-ß blockade to enhance responses to immune-checkpoint blockade.

Brain tumor-initiating cells export tenascin-C associated with exosomes to suppress T cell activity.

The dismal prognosis of glioblastoma is attributed in part to the existence of stem-like brain tumor-initiating cells (BTICs) that are highly radio- and chemo-resistant. New approaches such as therapies that reprogram compromised immune cells against BTICs are needed. Effective immunotherapies in glioblastoma, however, remain elusive unless the mechanisms of immunosuppression by the tumor are better understood. Here, we describe that while the conditioned media of activated T lymphocytes reduce the growth capacity of BTICs, this growth suppression was abrogated in live co-culture of BTICs with T cells. We present evidence that BTICs produce the extracellular matrix protein tenascin-C (TNC) to inhibit T cell activity in live co-culture. In human glioblastoma brain specimens, TNC was widely deposited in the vicinity of T cells. Mechanistically, TNC inhibited T cell proliferation through interaction with α5ß1 and αvß6 integrins on T lymphocytes associated with reduced mTOR signaling. Strikingly, TNC was exported out of BTICs associated with exosomes, and TNC-depleted exosomes suppressed T cell responses to a significantly lesser extent than control. Finally, we found that circulating exosomes from glioblastoma patients contained more TNC and T cell-suppressive activity than those from control individuals. Taken together, our study establishes a novel immunosuppressive role for TNC associated with BTIC-secreted exosomes to affect local and distal T lymphocyte immunity.