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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., COVID-19; University students; Professional career; Online education; Bangladesh

The Sundarbans, the largest mangrove forest of the world, delivers countless ecosystem services for the local livelihoods and the national economy, and contribute positively to the global environment. The forest resource-dependent communities (FRDCs) of the Sundarbans, including fishermen, crabbers, honey hunters, nipa leaf collectors and many others, are depending directly on the ecosystem and resources of the Sundarbans. The livelihood of FRDCs of the Sundarbans, however, is threatened incessantly by various climatic and non-climatic environmental changes. This study aims to identify the indicators of climate change-induced livelihood vulnerabilities of FRDCs of the Sundarbans. Climate change poses a major threat to the livelihoods of FRDCs by damaging forest health, which in turn reduces the productivity of forest resources. Thus, the FRDCs experience a dramatic change in income and employment opportunities. The FRDCs are compelled to change occupations to adjust to emerging situations. For example, nipa leaf collectors or honey hunters may involve in fishing, which would lead to overexploitation of fishing resources, and inadvertently affecting the ecosystem and the livelihood of the FRDCs. Incapable of dealing with precarious conditions, some may leave their primary occupation and migrate to nearby urban centers, thus intensifying the urban problems. Therefore, essential management plans and policies should be taken by the concerned authority involving both development partners and grass-root stakeholders. The directives should attempt to minimize the effect of climate change on the livelihoods of the FRDCs and to improve the benefits of the ecosystem services for the sustainable environmental and socioeconomic development.

The outbreak of the coronavirus disease (COVID-19) has affected and virtually changed the life and livelihoods of people across the world, and the forest resource-dependent communities (FRDCs) in the Sundarbans of Bangladesh are no exception. Aiming at identifying the changes in the livelihood and healthcare-seeking behavior of FRDCs during COVID-19, an in-depth interview approach was adopted. The FRDCs, including fishermen, crabbers, honey hunters, and nipa leaf (i.e., Golpata) collectors, have been experiencing an unprecedented event as the government-imposed sanctions on entering the Sundarbans - the only source of income in many cases. Left without any other source of income, some of them were engaged in illegal resource extraction, while most of the people of FRDCs have either remained unemployed or borrowed money at high interest to maintain the family. The financially marginalized FRDCs, thus, have no alternative but to seek medical assistance from the quacks or pharmacies. Without the collaborative interventions of the government and its development partners, the FRDCs are not going to change their fate from the ‘extremely poor.’

The coastal areas of Bangladesh are often hit by climate induced Cyclones which have devastating effects on livelihood of people. The aim of the study was to understand the long-term occupational effect of climate change induced cyclone on farmers in the coastal area. To address the objective of the study various qualitative methods such as in-depth interviews, focus group discussion and key informant interview were employed for data collection in 2020. The study was conducted in Kamarkhola union under Dacope upazila of Khulna district in Bangladesh. The study reveals that due to cyclone farmers faced various degrees of difficulties to maintain their livelihood in the post-disaster period. Cyclone Aila caused damage to the embankment in the area as a result many agricultural land experienced waterlogging for more than three years. Consequently farmers could not produce crops and created long-term unemployment of the agriculture depended households. Regular flooding of agricultural land decreased fertility of land because of increased salinity and siltation on top of the land. Therefore, the crops production reduced significantly when the farmers resumed cultivating. To cope with this situation, many marginal farmers and agricultural labourers have changed their occupation and are working as day labourers. Some of them also have migrated to neighbouring cities in search of work. To reduce the vulnerabilities, the farmers have suggested for implementation of a long-term disaster recovery plan by the government.

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-β 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-β blockade to enhance responses to immune-checkpoint blockade., Changes in ECM are of predictive value in pancreatic and colorectal cancer prognosis. Here, the authors perform a pan-cancer analysis and find a subset of ECM genes that is linked to TGF-β signalling signature and is correlated with immunotherapy failure.

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 α5β1 and αvβ6 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.

The ability to disseminate, invade and successfully colonise other tissues is a critical hallmark of cancer that involves remodelling of the extracellular matrix (ECM) laid down by fibroblasts 1. Moreover, Cancer-Associated-Fibroblasts (CAFs) produce key growth factors and cytokines as components of the ECM that fuel tumour growth, metastasis and chemoresistance, and immune response 2-4. ECM changes also predict prognosis in pancreatic 5 and colorectal cancers 6,7. Here, we examine the landscape of ECM-gene dysregulation pan-cancer and find that a subset of ECM genes is (i) dysregulated specifically in cancer, (ii) adversely prognostic, (iii) linked to TGF-beta signalling and transcription in Cancer-Associated-Fibroblasts, (iv) enriched in immunologically active cancers, and (v) predicts responses to Immune checkpoint blockade better than mutation burden, cytolytic activity, or an interferon signature, thus identifying a novel mechanism of immune evasion for patient stratification in precision immunotherapy and pharmacological modulation.

Background One of the key hallmarks of cancer is metastasis, which involves extensive extracellular matrix remodelling to permit extravasation from the primary tumour site before colonisation of distant sites. In this study, we defined the landscape of ECM-associated transcriptional dysregulation and performed in-silico associative analyses in terms of multiple -omics platforms, cellular composition and immunological parameters. Methods We defined the landscape of ECM gene dysregulation by integrating curated Gene Ontology ECM genes with genes differentially expressed between cancer and normal tissues from TCGA. ssGSEA scores for this set were then correlated with purity (ABSOLUTE), tested for stromal association using microdissected tumours and MethylCIBERSORT, and neoepitope counts derived using Topiary. Single-cell RNAseq data was used to validate CAF-origin. Linear models were used to identify transcriptomic, proteomic and genomic correlates, and finally, RNAseq data from three cohorts of PD1-blockade treated patients and 0.632 bootstrap evaluation of logistic regression or Random Forest models based on ECM genes, Cytolytic Activity, Mutational burden or their combinations was performed. Results A core set of 58 ECM genes is dysregulated and significantly enriched amongst genes differentially expressed between cancer and normal tissues pan-cancer. Those upregulated in cancers were found to be a negative prognostic factor pan-cancer and through integrative analysis of microdissected samples, deconvolution and single-cell RNAseq, were found to originate in Cancer Associated Fibroblasts. Transcriptome, proteome and genomics analyses implicated TGF-beta as a driver of this ECM-dysregulation signature and most notably, this programme was associated with heavily-mutated, neoantigen-high, CD8 high cancers, M1-macrophage-skewed tumours suggesting a role as a putative adaptation permitting immune evasion. Indeed, ECM dysregulation scores were significantly better predictors of response to PD1-blockade in pretreatment biopsies compared to cytolytic activity, an interferon gene signature, and mutational-burden, while TGF-beta expression alone was not, implicating a key role for CAF-specific ECM gene dysregulation in immune evasion. Conclusion A TGF-beta associated, CAF-derived signature of ECM-gene dysregulation broadly in operation across cancer types constitutes an immune evasion mechanism that indicates refractoriness to PD1-blockade. Citation Format: Ankur Ravinarayana Chakravarthy, Lubaba Khan, Nathan P. Bensler, Pinaki Bose, Daniel Diniz De Carvalho. A TGF-beta linked ECM-dysregulation programme in CAFs drives immune evasion and immunotherapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-362.