In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery. Investigations in mouse models of pancreatic cancer confirmed a functional role for basophils during tumor progression. The recruitment of basophils into TDLN relied partly upon the release of chemokine CCL7/MCP3 by "alternatively activated" monocytes, whereas basophil activation was induced by T-cell-derived IL3. Our results show how basophils recruited and activated in TDLNs under the influence of the tumor microenvironment regulate tumor-promoting Th2 inflammation in PDAC, helping in illuminating a key element of the immune milieu of pancreatic cancer.

We consider nonconservative, reversible spin systems, with unbounded discrete spins. We show that for a class of these dynamics in a high temperature regime, the relative entropy with respect to the equilibrium distribution decays exponentially in time, although the logarithmic-Sobolev inequality fails. To this end we prove a weaker modification of the logarithmic-Sobolev inequality.

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Summary. Cardiovascular ischaemic diseases are one of the main causes of death all over the world. In this class of pathologies, a quick diagnosis is essential for a good prognosis in reperfusive treatment. In particular, an automatic classification procedure based on statistical analysis of teletransmitted electrocardiograph ('ECG') traces would be very helpful for an early diagnosis. This work presents an analysis of ECG traces, either physiological or pathological, of patients whose 12-lead prehospital ECG has been sent to the 118 Dispatch Center in Milan by life-support personnel. The statistical analysis starts with a preprocessing step, where functional data are reconstructed from noisy observations and biological variability is removed by a non-linear registration procedure. Then, a multivariate functional k -means clustering procedure is carried out on reconstructed and registered ECGs and their first derivatives. Hence, a new semi-automatic diagnostic procedure, based solely on the ECG morphology, is proposed to classify ECG traces; finally, the performance of this classification method is evaluated.

Immune reconstitution plays a crucial role on the outcome of patients given T cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (hHSCT) for hematological malignancies. CD1d-restricted invariant NKT (iNKT) cells are innate-like, lipid-reactive T lymphocytes controlling infections, cancer, and autoimmunity. Adult mature iNKT cells are divided in two functionally distinct CD4+ and CD4− subsets that express the NK receptor CD161 and derive from thymic CD4+CD161− precursors. We investigated iNKT cell reconstitution dynamics in 33 pediatric patients given hHSCT for hematological malignancies, with a follow-up reaching 6 y posttransplantation, and correlated their emergence with disease relapse. iNKT cells fully reconstitute and rapidly convert into IFN-γ–expressing effectors in the 25 patients maintaining remission. CD4+ cells emerge earlier than the CD4− ones, both displaying CD161− immature phenotypes. CD4− cells expand more slowly than CD4+ cells, though they mature with significantly faster kinetics, reaching full maturation by 18 mo post-hHSCT. Between 4 and 6 y post-hHSCT, mature CD4− iNKT cells undergo a substantial expansion burst, resulting in a CD4+<CD4− NKT cell ratio similar to that found in healthy adults. In contrast with patients maintaining remission, iNKT cells failed to reconstitute in all eight patients experiencing disease relapse. These findings define the peripheral dynamics of human iNKT cells and suggest a contribution of these cells to maintain remission, possibly via early IFN-γ provision. Adoptive transfer of donor-derived iNKT cells into HLA-haploidentical patients failing to reconstitute these cells might represent a novel therapeutic option to prevent leukemia recurrence.

Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635–1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6 + ) levels or very low-IL-6 – levels. Objective: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. Methods and Results: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6 + STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6 − STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6 + STEMI and IL-6 − STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6 + STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 + STEMI and IL-6 − STEMI patients compared with controls. IL-6 + IL-10 + STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6 − IL-10 + STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.

The ratio between the prompt ψð2SÞ and J=ψ yields, reconstructed via their decays into μ þ μ − , is measured in Pb-Pb and p-p collisions at ffiffiffiffiffiffiffi ffi s NN p ¼ 2.76 TeV. The analysis is based on Pb-Pb and p-p data samples collected by CMS at the Large Hadron Collider, corresponding to integrated luminosities of 150 μb −1 and 5.4 pb −1 , respectively. The double ratio of measured yields ðN ψð2SÞ =N J=ψ Þ Pb-Pb = ðN ψð2SÞ =N J=ψ Þ p-p is computed in three Pb-Pb collision centrality bins and two kinematic ranges: one at midrapidity, jyj < 1.6, covering the transverse momentum range 6.5 < p T < 30 GeV=c, and the other at forward rapidity, 1.6 < jyj < 2.4, extending to lower p T values, 3 < p T < 30 GeV=c. The centralityintegrated double ratio changes from 0.45 AE 0.13ðstatÞ AE 0.07ðsystÞ in the first range to 1.67 AE 0.34ðstatÞ AE 0.27ðsystÞ in the second. This difference is most pronounced in the most central collisions.