Additional file 2: Clip 2. of Transient global ventricular dysfunction in an adolescent affected by pancreatic adenocarcinoma

Exam performed on May 23rd. Improvement in left ventricular function is observed, with mild diffuse hypokinesia and normal left ventricular geometry. (AVI 6992 kb

Lycoris sanguinea Maxim.

原著和名: キツネノカミソリ科名: ヒガンバナ科 = Amaryllidaceae採集地: 千葉県 四街道市 物井 (下総 四街道市 物井)採集日: 1983/3/20採集者: 萩庭丈壽整理番号: JH033663国立科学博物館整理番号: TNS-VS-98366

Flow-chart of HCMV-specific T-cell response.

<p>Immune control of HCMV infection in the 131 young patients enrolled in the study. During follow-up, 12/42 HCMV-seronegative and 89/89 HCMV-seropositive patients developed HCMV infection/immunity, for a total of 101 patients. Forty-three patients required pre-emptive therapy to control HCMV infection prior to development of specific immunity. Six patients died for underlying disease relapse. Of the 93 remaining patients, 88 (95%) were protected, while 5 (5%) were treated with additional courses of pre-emptive therapy because the steroid therapy employed for treating GvHD promoted reactivation of viral infection, with a viral load in blood reaching the established cutoff.</p

Probability of survival, transplant-related mortality and GvHD in the HSCT studied population.

<p>(A) event-free survival (EFS), (B) overall survival (OS): no significant difference was found by the log-rank test. (C) Transplantation–related mortality (TRM), and (D) acute and chronic GvHD were expressed as cumulative incidence, taking into account the appropriate competing risks: no difference was found by the Gray test. HCMV-seropositive and HCMV-seronegative young HSCT recipients are reported separately.</p

Characteristics of the 131 patients analyzed.

<p>TBI: total body irradiation; GvHD: graft <i>vs</i> host disease; CS-A: cyclosporine-A; MTX:methotrexate; ALG: anti-lymphocyte globulin methotrexate; ALG: anti-lymphocyte globulin.</p>*<p>Among patients with malignant disease.</p

Cumulative incidence of HCMV infection in 131 young patients receiving HSC transplantation.

<p>(A) HCMV-seropositive patients. (B) HCMV-seronegative patients. (C) HCMV viral load in 88 patients with self-resolving or no HCMV infection, and in 43 patients requiring antiviral treatment. Among patients receiving T-cell depleted transplantation (TCD), 14/28 were included in the pre-emptive treatment group. Similarly, 10/11 patients receiving cord blood transplantation (CBT) were included in the pre-emptive treatment group.</p

HCMV-specific T-cell response to HCMV infection in 4 young patients receiving HSCT transplantation.

<p>(A) Early specific CD4⁺and CD8⁺ T-cell response with no HCMV infection. (B) Delayed CD4⁺ and CD8⁺ T-cell response with high viral load in a patient pre-emptively treated. (C) Early CD8⁺ T-cell response which did not prevent HCMV infection until HCMV-specific CD4⁺ response appeared. (D) In the presence of acute and chronic GvHD requiring steroid treatment, specific immune reconstitution did not protect against HCMV infection, which required ganciclovir (GCV) treatment, and was eventually prevented by a protective CD4⁺ and CD8⁺ T-cell response.</p

Cumulative incidence of IFN-γ⁺ and IFN-γ⁺/IL-2⁺ CD4⁺ and CD8⁺ T-cell recovery in HSCT recipients.

<p>(A) HCMV-seropositive and (D) HCMV-seronegative young HSCT recipients. The cumulative curve indicating levels of protection during follow-up is also reported. Five (20%) of the 25 patients who developed HCMV-specific CD8+ T-cell response only a median time of 57 (16–340) days prior to appearance of CD4+ T-cells, had high DNAemia levels requiring antiviral treatment. The correlation (Spearman correlation test) between time to protection by HCMV-specific (B) CD4⁺ or (C) CD8⁺ T-cells and time to HCMV clearance from blood is shown. Within 12 months after transplantation, 95/131 patients developed specific T-cell immunity: 2 CD8+ only, and 93 both CD4 and CD8 T-cells. Of these 93, 85 developed specific immunity above the cutoff levels established for immune compromised patients (but 5 required antiviral treatment because of steroid therapy for GvHD), and 8 only levels above the cutoffs established for immune competent subjects (and were found to be also protected from reactivation).</p

DataSheet_1_Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry.docx

Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the “-omics” era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups.</p

Table_1_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.docx

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p