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Additional file 1: Figure S1. Generation of the atherosclerosis-prone hepatocyte-specific Ncor1 knockout mouse model. Figure S2. Validation of the hepatocyte-specific Ncor1 knockout mouse model. Figure S3. Food intake. 24 hours average food intake in L-Ncor1Hep+/+ and L-Ncor1Hep-/-mice. n = 11 L-Ncor1Hep+/+; n = 12 L-Ncor1Hep-/-. Figure S4. Hepatocyte-specific Ncor1 knockouts display a trend for increased plasma cholesterol and triglyceride levels. A Plasma total cholesterol concentrations in L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice n = 6 L-Ncor1Hep+/+; n = 9 L-Ncor1Hep-/-. B TC levels in lipoprotein subfractions of L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 6 L-Ncor1Hep+/+; n = 8 L-Ncor1Hep-/-. C TC levels in lipoprotein subfractions of L-Ncor1Hep+/+mice fed HCD or chow diets. Pooled samples of 5–7 mice per diet group. D TC levels in lipoprotein subfractions of L-Ncor1Hep-/-mice fed HCD or chow diets. Pooled samples of 5–7 mice per diet group. Figure S5. Hepatocyte Ncor1 deficiency alters biliary bile acid composition. Percentage of CA- and CDCA-derived bile acids in bile collected through cannulation in L-Ncor1Hep+/+ (WT) and L-Ncor1Hep-/- (KO) mice n = 11 L-Ncor1Hep+/+; n = 11 L-Ncor1Hep-/-. *p < 0.001 relative to L-Ncor1Hep+/+. Figure S6. Total fecal bile acid excretion. L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 12 L-Ncor1Hep+/+; n = 10 L-Ncor1Hep-/-. Figure S7. Relative expression of transcripts at the indicated times points: 24h (Zeitgeber ZT 17), 8h (ZT 1) and 16h (ZT 9). L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 3 L-Ncor1Hep+/+; n = 3 L-Ncor1Hep-/-.

Clelia Madeddu,1 Manuela Neri,2 Elisabetta Sanna,2 Sara Oppi,3 Antonio Macciò2 1Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 2Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy; 3Hematology and Transplant Center, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, ItalyCorrespondence: Antonio Macci&#x00F2A. Businco Hospital, ARNAS G. Brotzu, via Jenner, Cagliari, 09100, ItalyTel +390706754228Email antoniomaccio56@gmail.comAbstract: Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients.Keywords: hemoglobin, cancer-related anemia, chemotherapy-induced anemia, energy metabolism, inflammation, iron homeostasis, erythropoietin, interleukin-6

Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. This chronic immunometabolic disease evolves during decades in humans and encompasses different organs and immune cell types, as well as local and systemic processes that promote the progression of the disease. The most frequently used animal model to study these atherogenic processes and inter-organ crosstalk in a short time frame are genetically modified mouse models. Some models have been used throughout the last decades, and some others been developed recently. These models have important differences in cholesterol and lipoprotein metabolism, reverse cholesterol transport pathway, obesity and diabetes as well as inflammatory processes. Therefore, the disease develops and progresses differently in the various mouse models. Since atherosclerosis is a multifaceted disease and many processes contribute to its progression, the choice of the right mouse model is important to study specific aspects of the disease. We will describe the different mouse models and provide a roadmap to facilitate current and future atherosclerosis researchers to choose the right model depending on their scientific question.

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613 ), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.