This paper aims to investigate the association between perceived production risk of horticultural farms and access to finance from different finance providers. The collection of data was conducted ...among 434 farmers in Indonesia particularly farmers produced mango, mangosteen, chili and red onion. Production risk was measured by the coefficient of variation, skewness, kurtosis and the 25.sup.th percentile. Depending on the risk measure, a lower production risk was found for commercial credit from banks and flexible payments of inputs to kiosks. Conversely, we did not find any lower production risk associated with finance provided by farmers' associations and other sources such as family and friends. Results of this study are useful for policy makers, finance providers and supply chain actors in agriculture. For policy makers, the results of this study can help in designing policy to enhance farmers' access to finance, whereas finance providers and supply chain actors, such as traders, obtain insight into whether their financial provisions effectively reduce production risk.
The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. ...However, this observation does not exclude the existence of neoantigen-specific T cells in colorectal cancers with low mutation burden and the exploitation of their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous neoantigen-specific T cell responses could also be observed in patients diagnosed with mismatch repair-proficient colorectal cancers.
Whole-exome and transcriptome sequencing were performed on cancer and normal tissues from seven colorectal cancer patients diagnosed with mismatch repair-proficient tumors to detect putative neoantigens. Corresponding neo-epitopes were synthesized and tested for recognition by in vitro expanded T cells that were isolated from tumor tissues (tumor-infiltrating lymphocytes) and from peripheral mononuclear blood cells stimulated with tumor material.
Neoantigen-specific T cell reactivity was detected to several neo-epitopes in the tumor-infiltrating lymphocytes of three patients while their respective cancers expressed 15, 21, and 30 non-synonymous variants. Cell sorting of tumor-infiltrating lymphocytes based on the co-expression of CD39 and CD103 pinpointed the presence of neoantigen-specific T cells in the CD39
CD103
T cell subset. Strikingly, the tumors containing neoantigen-reactive TIL were classified as consensus molecular subtype 4 (CMS4), which is associated with TGF-β pathway activation and worse clinical outcome.
We have detected neoantigen-targeted reactivity by autologous T cells in mismatch repair-proficient colorectal cancers of the CMS4 subtype. These findings warrant the development of specific immunotherapeutic strategies that selectively boost the activity of neoantigen-specific T cells and target the TGF-β pathway to reinforce T cell reactivity in this patient group.
Aims/hypothesis
Biomarkers of endothelial dysfunction and low-grade inflammation are important in the pathogenesis of CVD and can potentially be modified by physical activity and sedentary behaviour. ...Effects of physical activity on biomarkers of endothelial dysfunction may be especially prominent in type 2 diabetes.
Methods
In the population-based Maastricht Study (
n
= 2363, 51.5% male, 28.3% type 2 diabetes, 15.1% prediabetes defined as impaired glucose tolerance and impaired fasting glucose), we determined biomarkers of endothelial dysfunction and low-grade inflammation, and combined
z
scores were calculated. Physical activity and sedentary behaviour were measured by activPAL. Linear regression analyses were used with adjustment for demographic, lifestyle and cardiovascular risk factors.
Results
The association between total, light, moderate-to-vigorous and vigorous intensity physical activity and sedentary time on the one hand and biomarkers of endothelial dysfunction on the other were generally significant and were consistently stronger in prediabetes and type 2 diabetes as compared with normal glucose metabolism status (
p
for interaction <0.05). Associations between physical activity and sedentary behaviour on the one hand and low-grade inflammation on the other were also significant and were similar in individuals with and without (pre)diabetes (
p
for interaction >0.05).
Conclusions/interpretation
Physical activity and sedentary behaviour are associated with biomarkers of endothelial dysfunction and low-grade inflammation. For biomarkers of endothelial dysfunction, associations between physical activity and sedentary behaviour were consistently stronger in (pre)diabetes than in normal glucose metabolism. Whether increasing physical activity or decreasing sedentary time can positively influence biomarkers of endothelial dysfunction in individuals with prediabetes and type 2 diabetes requires further study.
Graphical abstract
The nuclear protein high-mobility group box 1 (HMGB1) can be passively released by necrotic cells or secreted actively by several cell types to regulate immune and inflammatory responses, as well as ...tissue remodeling. We herein aimed to characterize the effect of insulin resistance on HMGB1 in adipose tissue and to examine its potential role as a metabolic regulator in β-pancreatic cells.
Plasma HMGB1 concentration and adipose HMGB1 expression were assessed in relation to obesity and insulin resistance. Cultured adipocytes from lean and obese patients were used to investigate the intracellular distribution and factors regulating HMGB1 release, as well as to test its effects on adipogenesis and lipid metabolism. A regulatory role for HMGB1 in insulin secretion was also investigated.
Circulating HMGB1 was positively associated with body mass index, while adipose HMGB1 mRNA levels correlated with the expression of inflammatory markers. Insulin resistance modified the intracellular distribution of HMGB1 in human adipocytes, with HMGB1 being predominantly nuclear in lean and obese normoglycemic individuals while localized to the cytosol in obese patients with type 2 diabetes. Adipocytes from lean individuals exposed to conditioned media from lipopolysaccharide-stimulated macrophages induced HMGB1 redistribution to the cytoplasm and release. HMGB1 treatment had no effect on differentiation and lipid metabolism in adipocytes. However, HMGB1, whose circulating levels correlated with postload insulin concentration, increased both insulin release and intracellular Ca(2+) concentration in INS-1 cells.
These findings show, for the first time, that HMGB1 expression and release by human adipocytes is altered by inflammatory conditions as those imposed by obesity and insulin resistance. Our data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion of β-pancreatic cells.
Epidemiological evidence regarding the relationship between fructose intake and intrahepatic lipid (IHL) content is inconclusive. We, therefore, assessed the relationship between different sources of ...fructose and IHL at the population level.
We used cross-sectional data from The Maastricht Study, a population-based cohort study (n = 3,981; mean ± SD age: 60 ± 9 years; 50% women). We assessed the relationship between fructose intake (assessed with a food-frequency questionnaire)-total and derived from fruit, fruit juice, and sugar-sweetened beverages (SSB)-and IHL (quantified with 3T Dixon MRI) with adjustment for age, sex, type 2 diabetes, education, smoking status, physical activity, and intakes of total energy, alcohol, saturated fat, protein, vitamin E, and dietary fiber.
Energy-adjusted total fructose intake and energy-adjusted fructose from fruit were not associated with IHL in the fully adjusted models (P = 0.647 and P = 0.767). In contrast, energy-adjusted intake of fructose from fruit juice and SSB was associated with higher IHL in the fully adjusted models (P = 0.019 and P = 0.009). Individuals in the highest tertile of energy-adjusted intake of fructose from fruit juice and SSB had a 1.04-fold (95% CI 0.99; 1.11) and 1.09-fold (95% CI 1.03; 1.16) higher IHL, respectively, in comparison with the lowest tertile in the fully adjusted models. Finally, the association for fructose from fruit juice was stronger in individuals with type 2 diabetes (P for interaction = 0.071).
Fructose from fruit juice and SSB is independently associated with higher IHL. These cross-sectional findings contribute to current knowledge in support of measures to reduce the intake of fructose-containing beverages as a means to prevent nonalcoholic fatty liver disease at the population level.
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•Pecan nutshell could be used as carbon source for production of BC by G. entanii.•Cellulose produced by G. entanii had high purity.•BC production by G. entanii using pecan nutshell ...is the first report.•Data obtained can be useful for the synthesis of methylcellulose from other BC.
Pecan nutshell is an abundant waste with a high content of carbohydrates. According to its chemical composition, pecan nutshell could be used as carbon source for Gluconacetobacter entanii, a bacterium that produces cellulose with high purity and nanometric characteristics. Bacterial cellulose (BC) was obtained from a static culture medium using pecan nutshell as carbon source and saccharose as control. Results showed that the pecan nutshell could be used as carbon source for production of BC. The cellulose yield ranged around 2.816 ± 0.040 g/L for 28 days. The morphological, structural and chemical properties of the cellulose produced were similar to those reported for others BC. The spectroscopic characterization indicated the chemical functionalization of BC and the reduction of its crystallinity. The production of BC with G. entanii using pecan nutshell as carbon source, is the first report. The BC could have potential use in chemical functionalization and in the preparation of biocomposites.
A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in ...patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC.
Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence.
We discovered that a previously unappreciated innate lymphocyte population (Lin
CD7
CD127
CD56
CD45RO
) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103
CD69
) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR
CD38
PD-1
) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes.
This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.
OBJECTIVES: To investigate whether higher circulating levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), and α1‐antichymotrypsin (ACT) are associated with worse cognitive function and decline ...in old age.
DESIGN: Two independent population‐based cohort studies.
SETTING: The Rotterdam Study (mean follow‐up 4.6 years) and the Leiden 85‐plus Study (maximal follow‐up 5 years).
PARTICIPANTS: Three thousand eight hundred seventy‐four individuals, mean age 72, from the Rotterdam Study, and 491 individuals, all aged 85, from the Leiden 85‐plus Study.
MEASUREMENTS: Both studies assessed global cognition, executive function, and memory. Linear regression analyses were used in the current study to investigate the associations between inflammatory markers and cognitive function and decline.
RESULTS: In the Rotterdam Study, higher levels of CRP and IL‐6 were cross‐sectionally associated with worse global cognition and executive function (P<.05). ACT was not associated with cognitive function. In the Leiden 85‐plus Study, estimates were similar for CRP, although not statistically significant. Higher IL‐6 levels were related to a steeper annual decline in memory function in the longitudinal analysis in the Leiden 85‐plus Study (P<.05). The effect of higher IL‐6 levels on global and memory function decline was stronger in apolipoprotein E (APOE) ɛ4 carriers (P‐interaction=.01) than in those who were not (P‐interaction=.05). In the Rotterdam Study, higher IL‐6 levels were related to a steeper annual decline in global cognition in APOE ɛ4 carriers only.
CONCLUSION: Systemic markers of inflammation are only moderately associated with cognitive function and decline and tend to be stronger in carriers of the APOE ɛ4 allele. Systemic markers of inflammation are not suitable for risk stratification.
The subjective experiences were assessed of cochlear implant (CI) users either wearing or not wearing a hearing aid (HA) at the contralateral ear.
Unilateral CI-recipients were asked to fill out a ...set of daily-life questionnaires on bimodal HA use, hearing disability, hearing handicap and general quality of life.
Twenty-six CI-recipients who regularly use a contralateral HA (bimodal group) and twenty-two CI-recipients who do not use a HA in the contralateral ear (unilateral group).
Comparisons between both groups (bimodal versus unilateral) showed no difference in self-rated disability, hearing handicap or general quality of life. However within the group of bimodal listeners, participants did report a benefit of bimodal hearing ability in various daily life listening situations.
Bimodal benefit in daily life can consistently be experienced and reported within the group of bimodal users.
Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center ...B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
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