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A primary challenge in single-cell RNA sequencing (scRNA-seq) studies comes from the massive amount of data and the excess noise level. To address this challenge, we introduce an analysis framework, named single-cell Decomposition using Hierarchical Autoencoder (scDHA), that reliably extracts representative information of each cell. The scDHA pipeline consists of two core modules. The first module is a non-negative kernel autoencoder able to remove genes or components that have insignificant contributions to the part-based representation of the data. The second module is a stacked Bayesian autoencoder that projects the data onto a low-dimensional space (compressed). To diminish the tendency to overfit of neural networks, we repeatedly perturb the compressed space to learn a more generalized representation of the data. In an extensive analysis, we demonstrate that scDHA outperforms state-of-the-art techniques in many research sub-fields of scRNA-seq analysis, including cell segregation through unsupervised learning, visualization of transcriptome landscape, cell classification, and pseudo-time inference. Accurate analysis of single-cell RNA sequencing (scRNA-seq) data is affected by issues including technical noise and high dropout rate. Here, the authors develop a hierarchical autoencoder, scDHA, which outperforms existing methods in scRNA-seq analyses such as cell segregation and classification.

Background: Nowadays the food production, supply and consumption chain represent a major cause of ecological pressure on the natural environment, and diet links worldwide human health with environmental sustainability. Food policy, dietary guidelines and food security strategies need to evolve from the limited historical approach, mainly focused on nutrients and health, to a new one considering the environmental, socio-economic and cultural impact—and thus the sustainability—of diets. Objective: To present an updated version of the Mediterranean Diet Pyramid (MDP) to reflect multiple environmental concerns. Methods: We performed a revision and restructuring of the MDP to incorporate more recent findings on the sustainability and environmental impact of the Mediterranean Diet pattern, as well as its associations with nutrition and health. For each level of the MDP we provided a third dimension featuring the corresponding environmental aspects related to it. Conclusions: The new environmental dimension of the MDP enhances food intake recommendations addressing both health and environmental issues. Compared to the previous 2011 version, it emphasizes more strongly a lower consumption of red meat and bovine dairy products, and a higher consumption of legumes and locally grown eco-friendly plant foods as much as possible.

Background Lombardy was the first European region most severely affected by the coronavirus disease 2019 pandemic in the spring of 2020. During that period, a substantial increase in socioeconomic inequality in total mortality was observed. This study aims to evaluate mortality data in the region up to September 2023 to verify whether the increased disparities between the poorest and the wealthiest municipalities persisted in the subsequent phases of the pandemic. Methods This study analyzed mortality data from January 2019 to September 2023 in Lombardy's municipalities by month and pandemic phases characterized by the predominance of the different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Municipalities were grouped according to the average income or pension of their residents. Age-standardized mortality rates (ASMRs) and the ASMR ratio between the poorest and the wealthiest municipalities were compared throughout the study period. Results In the pre-pandemic period (January 2019 - February 2020), the ASMR ratio at all ages between the poorest and the wealthiest municipalities fluctuated between 1.12 [95% confidence interval (CI): 1.07–1.16] and 1.29 (95% CI: 1.25–1.34). In March 2020, the ASMR ratio increased to 1.49 (95% CI: 1.45–1.52 95%) and returned to values registered before the pandemic thereafter. A similar pattern was observed in the analysis of mortality ≥ 65, using the average pension for group municipalities. Conclusions During the dramatic circumstances that the region faced in March 2020, pre-existing socioeconomic inequalities substantially widened. With the reorganization of the health system and the availability of vaccines, these disparities returned to the levels recorded before the pandemic.

The present overview of ovarian cancer epidemiology summarizes the main results for a network of case–control studies in Italy and from the Collaborative Group on Epidemiological Studies of Ovarian Cancer. There are consistent inverse relations between parity, oral contraceptive use and the risk of ovarian cancer. For other menstrual and hormonal factors (i.e. early age at menarche and late menopause), there are established associations, but of limited impact on ovarian cancer incidence on a population level. Serous and endometrioid ovarian cancers (but not mucinous or clear cell types) are related to current and recent use of hormone replacement therapy in menopause. There are no strong associations with alcohol and tobacco overall, but a direct link for tobacco with (borderline) mucinous cancers, of limited impact, however, on overall ovarian cancer mortality. There are direct associations of ovarian cancer risk with height and BMI, as well as possible relations with selected dietary factors – in the absence, however, of consistent findings – and a possible inverse association with physical activity. There is a strong association with a family history of ovarian cancer (and a few selected other neoplasms, including colorectum and endometrium). Recognized risk factors explain only a limited proportion of ovarian cancer cases on a population level. A key reason for the recent favourable trends of ovarian cancer incidence and mortality in several high-income countries is the widespread use of oral contraceptive in the generations born after 1930.

Published meta-analyses indicate significant but inconsistent incident type-2 diabetes (T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is now over a decade ago that a published meta-analysis used a predefined standard to identify valid studies. Considering valid studies only, and using random effects dose–response meta-analysis (DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relations would support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit >1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). The combined T2D–GI RR was 1.27 (1.15–1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that for the T2D–GL RR was 1.26 (1.15–1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet. The corresponding global DRM using restricted cubic splines were 1.87 (1.56–2.25) (p < 0.001, n = 10) and 1.89 (1.66–2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000 kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GL were robustly associated with incident T2D. Together with mechanistic and other data, this supports that consideration should be given to these dietary risk factors in nutrition advice. Concerning the public health relevance at the global level, our evidence indicates that GI and GL are substantial food markers predicting the development of T2D worldwide, for persons of European ancestry and of East Asian ancestry.

Abstract Background Advances in technologies, occupational hygiene and increased surveillance have reduced the excess mortality previously found in the construction industry. This study is aimed to evaluate cause-specific mortality in a recent cohort of construction workers. Methods We carried out a record-linkage cohort study based on the 2011 Italian census and the mortality archives (2012–2015), including 1 068 653 construction workers. We estimated mortality rate ratios (MRR) using Poisson regression models including terms for age and geographic area. Results Compared with non-manual workers, construction workers showed an excess mortality from all causes (MRR: 1.34), all neoplasms (MRR: 1.30), head and neck (MRR: 2.05), stomach (MRR: 1.56), liver (MRR: 1.62), lung (MRR: 1.80), prostate (MRR: 1.24) and bladder (MRR: 1.60) cancers, respiratory (MRR: 1.41) and liver (MRR: 1.79) diseases, all external causes (MRR: 1.87), falls (MRR: 2.87) and suicide (MRR: 1.58). Compared with manual workers in other industries, construction workers showed excess mortality from prostate (MRR: 1.27) and non-melanoma skin cancers (MRR: 1.95), all external causes (MRR: 1.14), falls (MRR: 1.94) and suicide (MRR: 1.18). Most of this excess mortality disappeared after adjusting for education, with the exception of prostate and non-melanoma skin cancers, all external causes, falls and suicide. Conclusions Construction workers are at high risk of dying from external causes, while the excess mortality found for several cancers, liver and respiratory diseases may be at least partially due to the high prevalence of low education and unfavorable lifestyle factors. The excess mortality from prostate cancer requires further evaluations.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) introduced in 2007, and updated in 2018, nutrition-related recommendations for cancer prevention. Previous studies generally reported inverse associations of breast cancer with the 2007 recommendations, while no study has yet evaluated the association with the 2018 guidelines. We investigated the association between adherence to the 2018 WCRF/AICR recommendations and breast cancer risk in a case–control study from Italy and Switzerland (1991–2008) including 3034 incident histologically-confirmed breast cancer cases and 3392 hospital controls. Adherence to the 2018 guidelines was summarized through a score incorporating eight recommendations (body fatness, physical activity, consumption of wholegrains/vegetables/fruit/beans, “fast foods” and other processed foods high in fat, starches, or sugars, red/processed meat, sugar-sweetened drinks, alcohol, breastfeeding), with higher scores indicating higher adherence. Odds ratios (OR) were estimated using multiple logistic regression models. We also conducted a meta-analysis including 15 additional studies using random-effects models. In our case–control study, adherence to the 2018 WCRF/AICR guidelines was inversely associated with breast cancer, with ORs of 0.60 (95% confidence interval (CI), 0.51–0.70) for a score ≥5.5 vs. ≤4.25, and of 0.83 (95% CI, 0.79–0.88) for a 1-point increment. In our study, 25% of breast cancers were attributable to low-to-moderate guideline adherence. In the meta-analysis, the pooled relative risks (RRs) were 0.73 (95% CI, 0.65–0.82, p heterogeneity among studies < 0.001) for the highest vs. the lowest WCRF/AICR score category, and 0.91 (95% CI, 0.88–0.94, p heterogeneity < 0.001) for a 1-point increment. This work provides quantitative evidence that higher adherence to the WCRF/AICR recommendations reduces the risk of breast cancer, thus opening perspectives for prevention.

Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case–control study (1992–2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium–low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55–0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56–1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60–1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28–0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention.

[...]the median age at death of patients who died and tested positive for SARS-CoV-2 infection was 82 years; 95% of them had at least one comorbidity, and 60% had at least three comorbidities before being infected. [...]total mortality in Italy showed that the COVID-19 pandemic had severely hit the country in the month of March, 2020, but there was a remarkable attenuation of the excess mortality in April and a lack of excess deaths in May. [...]total mortality is a key indicator of the COVID-19 effect; the excess total mortality in March and April, 2020, in Italy was substantial (ie, a total of over 45 000 deaths), corresponding to an overall excess about 60% greater than the number of officially registered COVID-19 deaths; there was a substantial under-registration of COVID-19 deaths in March, 2020, and a smaller under-registration in April, 2020; there was no residual excess total mortality in May, 2020, when COVID-19 deaths were probably over-registered.

While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill’s criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost–benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.