Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia

The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient’s fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments—blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory B-ALL, with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CAR-T infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT

On the number of limit cycles in asymmetric neural networks

The comprehension of the mechanisms at the basis of the functioning of complexly interconnected networks represents one of the main goals of neuroscience. In this work, we investigate how the structure of recurrent connectivity influences the ability of a network to have storable patterns and in particular limit cycles, by modeling a recurrent neural network with McCulloch-Pitts neurons as a content-addressable memory system. A key role in such models is played by the connectivity matrix, which, for neural networks, corresponds to a schematic representation of the "connectome": the set of chemical synapses and electrical junctions among neurons. The shape of the recurrent connectivity matrix plays a crucial role in the process of storing memories. This relation has already been exposed by the work of Tanaka and Edwards, which presents a theoretical approach to evaluate the mean number of fixed points in a fully connected model at thermodynamic limit. Interestingly, further studies on the same kind of model but with a finite number of nodes have shown how the symmetry parameter influences the types of attractors featured in the system. Our study extends the work of Tanaka and Edwards by providing a theoretical evaluation of the mean number of attractors of any given length $L$ for different degrees of symmetry in the connectivity matrices.Comment: 35 pages, 12 figure

General Critical Considerations

The aim of this study is to understand if criminalising bullying is a solution to counter and prevent the phenomenon. The Italian legislative proposal of criminalisation offers hints to discuss about a general problem while underlining that the penal solution is not the answer to solve a complex social problem as bullying (and cyberbullying) is. The creation of a specific crime determines a simplification of the question because it concentrates the attention on the dyad bully-victim, without considering the essential role of the group. Taking into account the role of the group and the relationship between the bully and the group implies a systemic approach

In vivo confocal microscopy of an apparent deep stroma corneal dystrophy: a case report

A 41-year-old white woman was referred to our Department to rule out the presence of a Fuch's corneal dystrophy. On slit-lamp biomicroscopy, small bilateral punctuate opacities appearing mostly in the posterior stroma were observed, suggesting a differential diagnosis of pre-Descemet's dystrophy as opposed to Cornea Farinata

The Condition of Foreigner as a Contact between Illegal Immigration and Trafficking in Human Beings/Smuggling of Migrants: a Report about Italian Legislation

Abstract Th

On the number of limit cycles in diluted neural networks

We consider the storage properties of temporal patterns, i.e. cycles of finite lengths, in neural networks represented by (generally asymmetric) spin glasses defined on random graphs. Inspired by the observation that dynamics on sparse systems have more basins of attractions than the dynamics of densely connected ones, we consider the attractors of a greedy dynamics in sparse topologies, considered as proxy for the stored memories. We enumerate them using numerical simulation and extend the analysis to large systems sizes using belief propagation. We find that the logarithm of the number of such cycles is a non monotonic function of the mean connectivity and we discuss the similarities with biological neural networks describing the memory capacity of the hippocampus.Comment: 10 pages, 11 figure

Combined Approach of Mechanochemistry and Electron Crystallography for the Discovery of 1D and 2D Coordination Polymers

Mechanochemical synthesis is an attractive preparative method that combines a green approach with versatility, efficiency, and rapidity of reaction. However, it often yields microcrystalline materials, and their small crystal size is a major hindrance to structure elucidation with conventional single-crystal or powder X-ray diffraction methods. This work presents the novel approach of combining mechanochemistry with electron diffraction techniques to elucidate the crystal structure of metal−organic compounds of zinc(II) and copper(II) with 2,6-pyridinedicarboxylic acid and 4,4′-bipyridine

A Shearless microfluidic device detects a role in mechanosensitivity for awcon neuron in Caenorhabditis elegans

AWC olfactory neurons are fundamental for chemotaxis toward volatile attractants in Caenorhabditis elegans. Here, it is shown that AWC(ON) responds not only to chemicals but also to mechanical stimuli caused by fluid flow changes in a microfluidic device. The dynamics of calcium events are correlated with the stimulus amplitude. It is further shown that the mechanosensitivity of AWC(ON) neurons has an intrinsic nature rather than a synaptic origin, and the calcium transient response is mediated by TAX-4 cGMP-gated cation channel, suggesting the involvement of one or more "odorant" receptors in AWC(ON) mechano-transduction. In many cases, the responses show plateau properties resembling bistable calcium dynamics where neurons can switch from one stable state to the other. To investigate the unprecedentedly observed mechanosensitivity of AWC(ON) neurons, a novel microfluidic device is designed to minimize the fluid shear flow in the arena hosting the nematodes. Animals in this device show reduced neuronal activation of AWC(ON) neurons. The results observed indicate that the tangential component of the mechanical stress is the main contributor to the mechanosensitivity of AWC(ON). Furthermore, the microfluidic platform, integrating shearless perfusion and calcium imaging, provides a novel and more controlled solution for in vivo analysis both in micro-organisms and cultured cells

Relation Between Platelet Response to Exercise and Coronary Angiographic Findings in Patients With Effort Angina

Background— Platelet reactivity is increased by exercise in patients with obstructive coronary artery disease (CAD) but not in patients with syndrome X. In this study, we prospectively investigated whether the platelet response to exercise might help distinguish, among patients with angina, those with obstructive CAD from those with normal coronary arteries (NCAs). Methods and Results— Venous blood samples were collected before and 5 minutes after exercise from 194 consecutive patients with stable angina. Platelet reactivity was measured by the platelet function analyzer (PFA)-100 system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time). Coronary angiography showed CAD in 163 patients (84%) and NCA in 31 patients (16%). Baseline closure time was shorter in NCA patients (78.0±16 versus 95.5±23 seconds, P <0.0001). With exercise, closure time decreased in CAD patients (−15.5 seconds; 95% confidence limits [CL], −13.0 to −18.0 seconds; P <0.0001), but increased in NCA patients (12.5 seconds; 95% CL, 7.4 to 17.7 seconds; P =0.0004). An increase in closure time with exercise ≥10 seconds had 100% specificity and positive predictive value for NCAs. Similarly, a decrease ≥10 seconds had 100% specificity and positive predictive value for CAD. A closure time change (increase or decrease) ≥10 seconds allowed a correct classification of 55% of all patients. Conclusions— Among patients with stable angina, the response of platelet reactivity to exercise was predictive of normal or stenosed coronary arteries at angiography. Specifically, an increase in closure time with exercise ≥10 seconds was invariably associated with the presence of NCA