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Background Surface tensiometry consented to characterize the surface free energy of geomaterials in an integrated and non-destructive way. A new surface tensiometry tool, based on the contact angle measurement of Polyperfluoromethylisopropyl Ether (TVS mud index?), has thus developed in the early 2000s. The TVS mud index? was for the first time employed from 2005 to 2010 for surface tensiometry characterization of peloids for pelotherapy from Abano Terme and Montegrotto Terme (Pa-dova, Italy). We aim to report the surface tensiometry application in the thermal field, and show the potentialities of TVS mud index as a marker for the non invasive quality control of the peloids and their maturation process. Methods The determination of the typical chemical-mineralogical characteristics of a Euganean Thermal Mud (ETM) and their surface tensiometry allowed us to demonstrate the link between the chemical data from X-ray fluorescence (XRF) analysis and they performed using a tensiometer to assess the quality of the peloid and its biological maturation process. Results The liquid test Polyperfluoromethylisopropyl Ether-based demonstrated the link between variations in volume elements and surface free energy of muddy matrices. The research results here showed that the TVS mud index? is linked to the chemical pattern of peloids. Conclusions The research work implemented in the period 2005-2010 showed the potentialities of surface tensiometry in the assessment of peloids for pelotherapy using Polyperfluoromethylisopropyl Ether as a liquid test. [ABSTRACT FROM AUTHOR]

From a clinical point of view, the frozen shoulder occurs in two stages: inflammatory and fibrous and contracted. Both inflammation and fibrosis are mediated by inflammatory cells such as cytokines, growth factors and immune cells such as macrophages, mast cells and T and B lymphocytes. From the inflammatory phase in which pain is predominant and in which neoangiogenesis and neurogenesis are found, a gradual transition to the fibrotic phase is agreed with differentiation of fibroblasts into myofibroblasts and imbalance of the turnover of the cellular matrix with production of type III collagen. This process begins in the rotator interval extended in the subsequent phases to the entire capsule. The inflammatory phase will result in pain for the patient, while the fibrosis and contracture phase will result in stiffness. [ABSTRACT FROM AUTHOR]

As for sport climbing, also for outdoor activities such as rafting and canyoning, a strong connection with geofeatures on a long and short time scale exists. For investigating this, three river segments were selected in the Sesia hydrographic basin (Sesia Val Grande UNESCO Global Geopark, Northwest Italy). Here, commercial rafting and canyoning activities are popular, and important geological features are present (Sesia Supervolcano, Insubric Line). The segments were investigated using partly IDRAIM (system for stream hydromorphological assessment, analysis, and monitoring). Bedrock features, confinement, sinuosity, bankfull bottom, morphological units, and steepness were characterized. The segments were hence divided in several reaches. Correlations on the long time scale were found mainly between the geology and bankfull bottom configuration, while sinuosity allowed us to highlight the possible structural control on the genesis of gorges. Moreover, the analysis of changes in a short time scale along the river segments after the extreme meteorological event occurred on 2–3 October 2020, highlighted a rapids difficulty variation, channels diversion, and woody–rocky debris accumulation in the bankfull, deeply influencing river activities. Through the proposed approach, new frontiers in the outreach of geosciences could be opened, especially in virtue of the several Sustainable Development Goals that could be achieved through river outdoor activities, among the others new employment opportunities for local operators. [ABSTRACT FROM AUTHOR]

The Osservatorio Termale Permanente (OTP) operated from 1996 to 2014 in the Italian and international therapeutic thermalism field. The main aim of OTP was the development of a multidisciplinary approach for the characterization of the quality of peloids for cutaneous application and their maturation process using different qualitative and quantitative analytic techniques opening at the Integrated Analytical Approach in the field of therapeutic thermalism. The main innovation introduced by OTP were rheology and surface tensiometry applications on peloids. The introduction of surface tensiometry included the skin as a fundamental element for the development of mud therapy protocols based on the bioadhesive properties of peloids. The interfacial investigations between peloids and skin led to the characterization of the exchange activity occurring during pelotherapy on the cutaneous surface in a non-invasive and fast way. On these bases, our work linked each other the multidisciplinarity approach to the study of hydrothermal resources performed by OTP with the concept of the participative methodology commonly applied to the development of projects in the field of development cooperation. This combined approach led us to develop a scientific proposal for the development of therapeutic thermalism in countries not yet improved in this field and characterized by the presence of hydrothermal resources. [ABSTRACT FROM AUTHOR]

The performance and reliability of Ultra-Low-Power (ULP) computing platforms are adversely affected by environmental temperature and process variations. Mitigating the effect of these phenomena becomes crucial when these devices operate near-threshold, due to the magnification of process variations and to the strong temperature inversion effect that affects advanced technology nodes in low-voltage corners, which causes huge overhead due to margining for timing closure. Supporting an extended range of reverse and forward body-bias, UTBB FD-SOI technology provides a powerful knob to compensate for such variations. In this work we propose a methodology to maximize energy efficiency at run-time exploiting body biasing on a ULP platform operating near-threshold. The proposed method relies on on-line performance measurements by means of Process Monitoring Blocks (PMBs) coupled with an on-chip low-power body bias generator. We correlate the measurement performed by the PMBs to the maximum achievable frequency of the system, deriving a predictive model able to estimate it with an error of 9.7% at 0.7 V. To minimize the effect of process variations we propose a calibration procedure that allows to use a PMB model affected by only the temperature-induced error, which reduces the frequency estimation error by 2.4x (from 9.7% to 4%). We finally propose a controller architecture relying on the derived models to automatically regulate at run-time the body bias voltage. We demonstrate that adjusting the body bias voltage against environmental temperature variations leads up to 2X reduction in the leakage power and a 15% improvement on the global energy consumption when the system operates at 0.7 V and 170 MHz. • A performance-aware body bias voltage controlling strategy is proposed. • The body bias regulation is operated by a software controller. • It exploits on on-chip frequency measurements and body bias generators. • The leakage current is reduced by 2X and the energy efficiency improved by 1.3X [ABSTRACT FROM AUTHOR]

Abstract This article presents an integrated self-aware computing model in a Heterogeneous Multicore Architecture (HMA) to mitigate the power dissipation of an Orthogonal Frequency-Division Multiplexing (OFDM) receiver. The proposed platform consists of template-based Coarse-Grained Reconfigurable Array (CGRA) devices connected through a Network-on-Chip (NoC) around a few Reduced Instruction-Set Computing (RISC) cores. The self-aware computing model exploits Feedback Control System (FCS) which constantly monitors the execution-time of each core and dynamically scales the operating frequency of each node of the NoC depending on the worst execution-time. Therefore, the performance of the overall system is equalized towards a desired level besides mitigating the power dissipation. Measurement results obtained from Field-Programmable Gate Array (FPGA) synthesis show up to 20.2% dynamic power dissipation and 16.8% total power dissipation savings. Since FCS technique can be employed for scaling the frequency and the voltage and on the other hand, voltage supply cannot be scaled on the FPGA-based prototyped platform, the implementation is also estimated in 28nm Ultra-Thin Body and Buried oxide (UTBB) Fully-Depleted Silicon-On-Insulator (FD-SOI) Application-Specific Integrated Circuit (ASIC) technology to scale voltage in addition to frequency and get more benefits in terms of dynamic power dissipation reduction. Subsequent to synthesizing the whole platform on ASIC and scaling the voltage and frequency simultaneously as a Dynamic Voltage and Frequency Scaling (DVFS) method, significant dynamic power dissipation savings by 5.97X against Dynamic Frequency Scaling (DFS) method were obtained. [ABSTRACT FROM AUTHOR]

Richter syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Two pathologic variants of RS are recognized: namely, the diffuse large B-cell lymphoma (DLBCL) variant and the rare Hodgkin lymphoma (HL) variant. Histologic documentation is mandatory to diagnose RS. The clinical suspicion of RS should be based on clinical signs and symptoms. Differential diagnosis between CLL progression and RS and choice of the biopsy site may takeadvantageofpositronemissiontomography/computed tomography. Molecular lesions of regulators of proliferation (CDKN2A, NOTCH1, MYC) and apoptosis (TP53) overall associatewith~90% of DLBCL-type RS, whereas the biology of the HL-type RS is largely unknown. The prognosis of the DLBCL-type RS is unfavorable; the outcome of HL-type RS appears to be better. The most important RS prognostic factor is the clonal relationship between the CLL and the aggressive lymphoma clones, with clonally unrelated RS having a better prognosis. Rituximab-containing combination chemotherapy for DLBCL is the most widely used treatment in DLBCL-type RS. Fit patients who respond to induction therapy should be offered stem cell transplantation (SCT) to prolong survival. Adriamycin, bleomycin, vinblastine, and dacarbazine is the preferred regimen for the HL-type RS, and SCT consolidation is less used in this condition. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper is to design and evaluate an authoring tool to support users in documenting knowledge using social software-based platforms in order to improve information sharing within organizations. Facilitating the creation of such content has been identified as a critical point for the acceptance of similar platforms.Design/methodology/approach The authors propose a general framework to design and assess technological solutions that positively affects users’ contribution – and, as a consequence, users’ engagement – when knowledge is externalized, made persistent and shared by using semantic wikis. The definition of the framework has been derived from a case study on operational knowledge management. This framework revolves around interaction with actual users for both design and evaluation. The latter exploits usability tests based on the System Usability Scale and analysis based on the grounded theory.Findings The framework proved to be effective when applied for a solution for the authors’ case study. The results of the designed tool were well accepted, and the tool was characterized by its users as having high usability. A limitation that emerged is related to the ability to support authors not just in creating documentation but also in maintaining it, an aspect that needs to be better addressed in the future.Originality/value The presented framework can be instantiated for similar platforms and provides a common ground for assessment of tools. The produced tool significantly simplifies the production of documentation related to community best practices. Valuable user feedbacks were collected about possible improvements for tools supporting authors. [ABSTRACT FROM AUTHOR]

Ultralow-power embedded systems have recently started the move to multicore designs. Aggressive voltage scaling techniques have the potential to reduce the power consumption within the admitted envelope, but memory operations on standard six-transistor static RAM (6T-SRAM) cells become unreliable at low voltages. While standard cell memory (SCM) overcomes this limitation, it has much lower area density than SRAM, and thus it is too costly. On the other hand, several applications have inherent tolerance to computation errors, and executing such workloads with approximation has already proven a viable way to reduce energy consumption. In this paper, we propose a novel HW/SW approach to design energy-efficient ultralow-power systems which combine the key ideas of approximate computing and hybrid memory systems featuring both SCM and 6T-SRAM. We introduce a novel hardware support to split error-tolerant data so to host most significant bits in the SCM and least significant bits (LSBs) in the 6T-SRAM. This allows to power the memory system at a low voltage while ensuring correct operation by binding possible (flip-bit) errors to the LSBs only. In addition, by organizing 6T-SRAM banks into multiple and independent voltage domains we enable fine-grained, software-controlled voltage switching policies. At the software level, we propose language constructs to specify what regions of code and what variables are tolerant to approximation, plus compiler support to optimize data placement. Experimental results show that our proposal can reduce the energy consumption of the memory system by 47% on average, always complying with the result accuracy required by practical applications constraints. [ABSTRACT FROM PUBLISHER]

High-performance computing systems are moving towards 2.5D and 3D memory hierarchies, based on High Bandwidth Memory (HBM) and Hybrid Memory Cube (HMC) to mitigate the main memory bottlenecks. This trend is also creating new opportunities to revisit near-memory computation. In this paper, we propose a flexible processor-in-memory (PIM) solution for scalable and energy-efficient execution of deep convolutional networks (ConvNets), one of the fastest-growing workloads for servers and high-end embedded systems. Our co-design approach consists of a network of Smart Memory Cubes (modular extensions to the standard HMC) each augmented with a many-core PIM platform called NeuroCluster. NeuroClusters have a modular design based on NeuroStream coprocessors (for Convolution-intensive computations) and general-purpose RISC-V cores. In addition, a DRAM-friendly tiling mechanism and a scalable computation paradigm are presented to efficiently harness this computational capability with a very low programming effort. NeuroCluster occupies only 8 percent of the total logic-base (LoB) die area in a standard HMC and achieves an average performance of 240 GFLOPS for complete execution of full-featured state-of-the-art (SoA) ConvNets within a power budget of 2.5 W. Overall 11 W is consumed in a single SMC device, with 22.5 GFLOPS/W energy-efficiency which is 3.5X better than the best GPU implementations in similar technologies. The minor increase in system-level power and the negligible area increase make our PIM system a cost-effective and energy efficient solution, easily scalable to 955 GFLOPS with a small network of just four SMCs. [ABSTRACT FROM AUTHOR]

This article presents an ultra-low-power parallel computing platform and its system-on-chip (SoC) embodiment, targeting a wide range of emerging near-sensor processing tasks for Internet of Things (IoT) applications. The proposed SoC achieves 193 million operations per second (MOPS) per mW at 162 MOPS (32 bits), improving the first-generation Parallel Ultra-Low-Power (PULP) architecture by 6.4 and 3.2 times in performance and energy efficiency, respectively. [ABSTRACT FROM AUTHOR]

Treatment options for chronic lymphocytic leukemia (CLL) have improved with the introduction of the B-cell receptor inhibitors ibrutinib and idelalisib, and of the BCL2 inhibitor venetoclax. While awaiting the results of head to head comparisons between novel agents and chemoimmunotherapy, predictive biomarkers can assist physicians in treatment tailoring. Though novel agents have modified the landscape of predictors at the time of treatment requirement, the usefulness of historical CLL prognostic biomarkers is still up-to-date when considering anticipation of time to first treatment. This review discusses: (i) disease-related (TP53 defects, immunoglobulin gene mutations), therapy-related (duration of remission), and patient-related (age, comorbidities) biomarkers that can be used in the clinical practice to inform CLL treatment decision either at the time of first line therapy and disease relapse; and (ii) the need of new biomarkers to re-define high-risk CLL because of the questioning by novel agents of historical prognostic factors. [ABSTRACT FROM AUTHOR]

Accessible and real-time genotyping for diagnostic, prognostic, or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. In this study, we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pretreatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with >90% sensitivity and -100% specificity. Plasma cfDNA genotyping also allowed for the recovery of mutations that were undetectable in the tissue biopsy, conceivably because, due to spatial tumor heterogeneity, they were restricted to clones that were anatomically distant from the biopsy site. Longitudinal analysis of plasma samples collected under rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) chemo therapy showed a rapid clearance of DLBCL mutations from cfDNA among responding patients. Conversely, among patients who were resistant to R-CHOP, basal DLBCL mutations did not disappear from cfDNA. In addition, among treatment-resistant patients, new mutations were acquired in cfDNA that marked resistant clones selected during the clonal evolution. These results demonstrate that cfDNA genotyping of DLBCL is as accurate as genotyping of the diagnostic biopsy to detect clonally represented somatic tumor mutations and is a real-time and noninvasive approach to tracking clonal evolution and the emergence of treatment-resistant clones. [ABSTRACT FROM AUTHOR]

Splenic marginal zone lymphoma is a rare mature B-cell malignancy involving the spleen, bone marrow and blood. Over the past years, the rapid expansion of sequencing technologies allowing the genome-wide assessment of genomic, epigenetic and transcriptional changes has revolutionized our understanding of the biological basis of splenic marginal zone lymphoma by providing a comprehensive and unbiased view of the genes/pathways that are deregulated in this disease. NF-κB is a family of transcription factors that plays critical roles in development, survival, and activation of B lymphocytes. Consistent with the physiological involvement of NF-κB signalling in proliferation and commitment of mature B-cells to the marginal zone of the spleen, many oncogenic mutations involved in constitutive activation of the NF-κB pathway were recently identified in splenic marginal zone lymphoma. This review describes the progress in understanding the mechanism of NF-κB activation in splenic marginal zone lymphoma, including molecular, epigenetic and post-transcriptional modifications of NF-κB genes and of upstream pathways, and discusses how information gained from these efforts has provided new insights on potential targets of diagnostic, prognostic and therapeutic relevance for splenic marginal zone lymphoma. [ABSTRACT FROM AUTHOR]

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukaemia (CLL) is a molecularly heterogeneous disease as revealed by recent genomic studies. Among genetic lesions that are recurrent in CLL, few clinically validated prognostic markers, such as TP53 mutations and 17p deletion, are available for the use in clinical practice to guide treatment decisions. Recently, several novel molecular markers have been identified in CLL. Though these mutations have not yet gained the qualification of predictive factors for treatment tailoring, they have shown to be promising to refine the prognostic stratification of patients. The introduction of targeted drugs is changing the genetics of CLL, and has disclosed the acquisition of previously unexpected drug resistant mutations in signalling pathway genes. Ultra-deep next generation sequencing has allowed to reach deep levels of resolution of the genetic portrait of CLL providing a precise definition of its subclonal genetic architecture. This approach has shown that small subclones harbouring drug resistant mutations anticipate the development of a chemorefractory phenotype. Here we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterise the clinical implications of old and new molecular lesions in the setting of both conventional chemo-immunotherapy and targeted drugs. [ABSTRACT FROM AUTHOR]

Ultra-low power operation and extreme energy efficiency are strong requirements for a number of high-growth application areas, such as E-health, Internet of Things, and wearable Human–Computer Interfaces. A promising approach to achieve up to one order of magnitude of improvement in energy efficiency over current generation of integrated circuits is near-threshold computing. However, frequency degradation due to aggressive voltage scaling may not be acceptable across all performance-constrained applications. Thread-level parallelism over multiple cores can be used to overcome the performance degradation at low voltage. Moreover, enabling the processors to operate on-demand and over a wide supply voltage and body bias ranges allows to achieve the best possible energy efficiency while satisfying a large spectrum of computational demands. In this work we present the first ever implementation of a 4-core cluster fabricated using conventional-well 28 nm UTBB FD-SOI technology. The multi-core architecture we present in this work is able to operate on a wide range of supply voltages starting from 0.44 V to 1.2 V. In addition, the architecture allows a wide range of body bias to be applied from −1.8 V to 0.9 V. The peak energy efficiency 60 GOPS/W is achieved at 0.5 V supply voltage and 0.5 V forward body bias. Thanks to the extended body bias range of conventional-well FD-SOI technology, high energy efficiency can be guaranteed for a wide range of process and environmental conditions. We demonstrate the ability to compensate for up to 99.7% of chips for process variation with only ±0.2 V of body biasing, and compensate temperature variation in the range −40 °C to 120 °C exploiting −1.1 V to 0.8 V body biasing. When compared to leading-edge near-threshold RISC processors optimized for extremely low power applications, the multi-core architecture we propose has 144× more performance at comparable energy efficiency levels. Even when compared to other low-power processors with comparable performance, including those implemented in 28 nm technology, our platform provides 1.4× to 3.7× better energy efficiency. [ABSTRACT FROM AUTHOR]

We show that a self-mixing interferometer can supply not only to the usual optical-phase signal cos 2ks( $t$ ) of the external reflector displacement $s(t)$ , but also the attitude signal $P(a$ ) because of the dependence of power from the angle a between wavevector k and normal n to the target reflective surface. By proper interrogation of $P(a$ ) along two orthogonal components of tilt and yaw, the two angles can be measured simultaneously, together with the displacement, in a single self-mixing interferometer channel implemented by a single-laser diode and monitor photodiode combination. [ABSTRACT FROM AUTHOR]

Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant treatment advancement in chronic lymphocytic leukemia (CLL). In the new scenario of targeted agents, there is an increasing interest in identifying patients who gain the maximum benefit from FCR. In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR, the combination of three biomarkers that are widely tested before treatment (IGHV mutation status, 11q deletion and 17p deletion; available in 80% of the study cohort) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28% of all cases. The majority of very low-risk patients (71%) remained free of progression after treatment and their hazard of relapse decreased after 4 years from FCR. The life expectancy of very low-risk patients (91% at 5 years) was superimposable to that observed in the matched normal general population, indicating that neither the disease nor complications of its treatment affected survival in this favorable CLL group. These findings need a prospective validation and may be helpful for the design of clinical trials aimed at comparing FCR to new targeted treatments of CLL, and, possibly, for optimized disease management. [ABSTRACT FROM AUTHOR]

Objective: The severity of central sleep apnoea (CSA), a common comorbidity in patients with chronic heart failure (CHF) and reduced ejection fraction, markedly decreases from the supine to the lateral sleeping position, with no difference between the left and right positions. The mechanisms responsible for this beneficial effect have not yet been elucidated.Methods: We tested the hypothesis that CSA attenuation in the left lateral position is due, at least in part, to an improvement in cardiac haemodynamics. Sixteen CHF patients (male, aged 60 ± 7 years, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction [LVEF] 30% ± 5%) with moderate-to-severe CSA underwent two consecutive tissue Doppler echocardiography examinations in random order, one in the left lateral position (90°) and the other in the supine position (0°). The following parameters were obtained: left ventricular end-diastolic volume (LVEDV) and LVEF, left atrial volume (LAV) and right atrial volume (RAV), mitral regurgitation (MR), cardiac output (CO), transmitral protodiastolic (E) wave deceleration time (DT), E/e' ratio, tricuspid annular plane systolic excursion (TAPSE), and right ventricular-atrial gradient (RVAG).Results: The LAV, MR, E/e', RAV, and RVAG significantly increased, whereas the LVEF and TAPSE significantly decreased in the left lateral position. All changes, however, were of negligible clinical significance. No significant changes were observed in CO, DT, and LVEDV.Conclusions: This study shows that the reduction of CSA severity from the supine to the left lateral position in patients with CHF is not due to an improvement in cardiac haemodynamics. Other, noncardiac factors are likely to represent the main cause. [ABSTRACT FROM AUTHOR]

Background The increasing global importance of Rift Valley fever (RVF) is clearly demonstrated by its geographical expansion. The presence of a wide range of host and vector species, and the epidemiological characteristics of RVF, have led to concerns that epidemics will continue to occur in previously unaffected regions of Africa. The proximity of the Sahrawi territories of Western Sahara to endemic countries, such as Mauritania, Senegal, and Mali with periodic isolation of virus and serological evidence of RVF, and the intensive livestock trade in the region results in a serious risk of RVF spread in the Sahrawi territories, and potentially from there to the Maghreb and beyond. A sero-epidemiological survey was conducted in the Saharawi territories between March and April 2008 to investigate the possible presence of the RVF virus (RVFV) and associated risk factors. A two-stage cluster sampling design was used, incorporating 23 sampling sites. Results A total of 982 serum samples was collected from 461 sheep, 463 goats and 58 camels. Eleven samples (0.97%) tested positive for IgG against the RVFV. There were clusters of high seroprevalence located mostly in the Tifariti (7.69%) and Mehaires (7.14%) regions, with the Tifariti event having been found in one single flock (4/26 positive animals). Goats and older animals were at a significantly increased risk being seropositive (p = 0.007 and p = 0.007, respectively). Conclusion The results suggest potential RVF activity in the study area, where intense livestock movement and trade with neighbouring countries might be considered as a primary determinant in the spread of the disease. The importance of a continuous field investigation is reinforced, in light of the risk of RVF expansion to historically unaffected regions of Africa. [ABSTRACT FROM AUTHOR]

TP53 mutations are strong predictors of poor survival and refractoriness in chronic lymphocytic leukemia (CLL) and have direct implications for disease management. Clinical information on TP53 mutations is limited to lesions represented in >20% leukemic cells. Here, we tested the clinical impact and prediction of chemorefractoriness of very small TP53 mutated subclones. The TP53 gene underwent ultra-deep-next generation sequencing (NGS) in 309 newly diagnosed CLL. A robust bioinformatic algorithm was established for the highly sensitive detection of few TP53 mutated cells (down to 3 out of ∼1000 wild-type cells). Minor subclones were validated by independent approaches. Ultra-deep-NGS identified small TP53 mutated subclones in 28/309 (9%) untreated CLL that, due to their very low abundance (median allele frequency: 2.1%), were missed by Sanger sequencing. Patients harboring small TP53 mutated subclones showed the same clinical phenotype and poor survival (hazard ratio = 2.01; P = .0250) as those of patients carrying clonal TP53 lesions. By longitudinal analysis, small TP53 mutated subclones identified before treatment became the predominant population at the time of CLL relapse and anticipated the development of chemorefractoriness. This study provides a proof-of-principle that very minor leukemia subclones detected at diagnosis are an important driver of the subsequent disease course. [ABSTRACT FROM AUTHOR]

Abstract: Next generation sequencing (NGS) technology has led to a burst of disease-relevant molecular information in a variety of lymphoid tumors, including chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, Waldenström macroglobulinemia, hairy cell leukemia, and splenic marginal zone lymphoma. Beside disclosing comprehensive catalogs of somatic mutations and new insights into the genes that contribute to cellular transformation, NGS has also provided molecular clues useful for addressing a number of unmet clinical needs in the field of B-cell tumor management, including biomarkers for disease diagnosis and classification improvement (i.e. mutations of BRAF, MYD88 and NOTCH2), and new targets to be translated into therapeutic interventions (i.e. BCR, TLR, NOTCH, NF-κB and MAPK signaling pathways). This review summarizes the molecular lesions of signaling pathways that have been discovered in B-cell lymphoproliferative disorders by NGS studies. [Copyright &y& Elsevier]

Abstract: The human genome era heralded a fundamental progress in the field of cancer genetics that shifted from a candidate gene approach toward global views of genomes and transcriptomes. Whole genome/exome sequencing has disclosed the genetic landscape of several hematologic tumors, providing comprehensive catalogs of somatic mutations and new insights into the genes that contribute to cellular transformation. Thanks to these technical progresses, research on the molecular pathogenesis of chronic lymphocytic leukemia (CLL) has also advanced at a sustained pace in recent times revealing NOTCH1, SF3B1, BIRC3, and MYD88 as the most recurrently (>5%) mutated genes that have been identified in CLL. Beside mutations of cancer related genes, another mechanism involved in disease initiation and progression of mature B-cell tumors, including CLL, is represented by B cell receptor (BCR) signaling. The BCR plays a central role in disease pathogenesis and, consequently, BCR signaling might represent a suitable target for therapy in many patients. Currently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, which acts downstream the BCR signaling pathway, appears to be particularly promising and shows important clinical activity in CLL. [Copyright &y& Elsevier]

Genetic lesions and B-cell receptor (BCR) signaling are both oncogenic drivers in chronic lymphocytic leukemia (CLL). However, scant data are available on preferential associations between specific genetic alterations and stereotyped BCR subsets. By analyzing 1419 cases, 2 CLL subsets (2 and 8) harboring stereotyped BCR are enriched in specific molecular alterations influencing disease course. SF3B1 mutations are the genetic hallmark of IGHV3-21-CLL belonging to subset 2 (52%) but are evenly represented in nonstereotyped IGHV3-21-CLL. Trisomy 12 (87%) and NOTCH1 mutations (62%) characterize IGHV4-39-CLL belonging to subset 8 but occur with the expected frequency in IGHV4-39-CLL with heterogeneous BCR. Clinically, co-occurrence of SF3B1 mutations and subset 2 BCR configuration prompts disease progression in IGHV3-21-CLL, whereas cooperation between NOTCH1 mutations, + 12, and subset 8 BCR configuration invariably primes CLL transformation into Richter syndrome. These findings provide a proof of concept that specific stereotyped BCR may promote or select molecular lesions influencing outcome. [ABSTRACT FROM AUTHOR]

The identification of new genetic lesions in chronic lymphocytic leukemia (CLL) prompts a comprehensive and dynamic prognostic algorithm including gene mutations, chromosomal abnormalities, and their changes during clonal evolution. By integrating mutational and cytogenetic analysis in 1274 CLL samples, and by using both a training-validation and a time-dependent design, four CLL subgroups were hierarchically classified: i) high-risk, harboring TP53 and/or BIRC3 abnormalities (10-year survival:29%); ii) intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 (10-year survival:37%); iii) low-risk, harboring +12 or a normal genetics (10-year survival:57%); iv) very low-risk, harboring del13q14 only, whose 10-year survival (69.3%) did not significantly differ from a matched general population. This integrated mutational and cytogenetic model independently predicted survival, improved CLL prognostication accuracy compared to FISH karyotype (p<0.0001), and was externally validated in an independent CLL cohort. Clonal evolution from lower to higher risk implicated the emergence of NOTCH1, SF3B1 and BIRC3 abnormalities in addition to TP53 and 11q22-q23 lesions. By taking into account clonal evolution through time-dependent analysis, the genetic model maintained its prognostic relevance at any time from diagnosis. These findings may have relevant implications for the design of clinical trials aimed at assessing the use of mutational profiling to inform therapeutic decisions. [ABSTRACT FROM AUTHOR]

The tensometric vs. skin approach (TVS modelling®) is a non-invasive method based on the permutability principle of tensiometry. TVS modelling® is a technologic model that can evaluate the reproducibility of the matrix of thermal mud, its degree of maturation and consequently its skin affinity, in a non-destructive way. This is an essential pre-condition for defining the objective scientific protocols. The surface energy profile of the matrixes is created by a Tenskinmeter®, a tensiometer modified by us for tensiometric measurements on skin. The development of a chemico-mineralogical index (Ichmi ) based on X-ray fluores-cence analysis allows the typical chemico-mineralogical constituents of thermal muds to be determined. The combined TVS-Ichmi approach developed here demonstrates the intercon-nections between the typical chemico-mineralogical components of a Euganean Thermal Mud (ETM) and its energy surface properties. The combined approach also demonstrates the interconnections at the interface between Ichmi and the skin affinity of the mud matrix, revealing their typical functional and therapeutic effects. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work is to investigate surface energy properties of various raw coffee bean species (tensiometric approach) and to develop a tensiometric marker based on contact angle measurements of Fomblin HC/25 drops, a perfluoropolyether phosphate (PFPE), to distinguish different species of raw coffee beans. To create measurable contact angles, raw coffee beans were pre-selected according to the endosperm surface morphology (smooth surface) and affixed to a specifically developed support. The tensiometric method was developed using contact angle method (CA) and calculation models such as Owens, Wendt and Kaelble. Results show the tensiometric properties of raw coffee beans expressed as surface free energy (SFE) and the capability of the marker to distinguish species. This work could create interesting prospects for quality control at the product source, storage conditions, and for industrial process evaluation of roasting and drying. [Copyright &y& Elsevier]

The article presents a study on 605 patients with chronic lymphocytic leukemia (CLL) focusing on the impact of NOTCH1 and SFB3 mutations on the risk of transformation of CLL to Richter syndrome (RS). Techniques like Sanger sequencing, flow cytometry and multivariate analysis were used during the study. The SFB3 mutations showed no impact on RS development and were absent in all the CLL patients. 40 to 50 percent of NOTCH1 mutated patients developed RS.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and shows a remarkable heterogeneity in the clinical course. Understand the genetic basis of CLL may help in clarifying the molecular bases of this clinical heterogeneity. Recurrent chromosomal aberrations at 13q14, 12q, 11q22-q23 and 17p13, and TP53 mutations are the first genetic lesions identified as drivers of the disease. While some of these lesions are associated with poor outcome (17p13 deletion, TP53 mutations and, to a lesser extent, 11q22-q23 deletion) others are linked to a favorable course (13q14 deletion as sole aberration). Recently, next generation sequencing has revealed additional recurrent alterations in CLL targeting the NOTCH1, SF3B1, and BIRC3 genes. NOTCH1, SF3B1, and BIRC3 lesions provide: i) new insights on the mechanisms of leukemogenesis, tumor progression and chemoresistance in this leukemia; ii) new biomarkers for the identification of poor risk patients, having individually shown correlations with survival in CLL; and iii) new therapeutic targets, especially in the setting of high risk disease. This review will summarize the most important genetic aberrations in CLL and how our improved knowledge of the genome of leukemic cells may translate into improved patients' management. [ABSTRACT FROM AUTHOR]

The genetic lesions identified to date do not fully recapitulate the molecular pathogenesis of chronic lymphocytic leukemia (CLL) and do not entirely explain the development of severe complications such as chemorefractoriness. In the present study, BIRC3, a negative regulator of noncanonical NF-&κgr;Β signaling, was investigated in different CLL clinical phases. BIRC3 lesions were absent in monoclonal B-celi lymphocytosis (0 of 63) and were rare in CLL at diagnosis (13 of 306, 4%). Conversely, BIRC3 disruption selectively affected 12 of 49 (24%) fludarabine-refractory CLL cases by inactivating mutations and/or gene deletions that distributed in a mutually exclusive fashion with TP53abnormalities. In contrast to fludarabinerefractory CLL, progressive but fludarabine-sensitive patients were consistently devoid of BIRC3 abnormalities, suggesting that BIRC3 genetic lesions associate specifically with a chemorefractory phenotype. By actuarial analysis in newly diagnosed CLL (η = 306), BIRC3 disruption identified patients with a poor outcome similar to that associated with TP53 abnormalities and exerted a prognostic role that was independent of widely accepted clinical and genetic risk factors. Consistent with the role of BIRC3 as a negative regulator of NF-&κgr;Β, biochemical studies revealed the presence of constitutive noncanonical NF-&κgr;Β activation in fludarabinerefractory CLL patients harboring molecular lesions of BIRC3. These data identify BIRC3 disruption as a recurrent genetic lesion of high-riskCLL devoid of TP53abnormalities. [ABSTRACT FROM AUTHOR]

Analysis of the chronic lymphocytic leukemia (CLL) coding genome has recently disclosed that the NOTCH1 proto-oncogene is recurrently mutated at CLL presentation. Here we assessed the prognostic role of NOTCH1 mutations in CLL. Two series of newly diagnosed CLL were utilized as training (n=309) and validation (n=230) cohorts. NOTCH1 mutations occurred in 11.0% and 11.3% CLL of the training and validation series, respectively. In the training series, NOTCH1 mutations led to a 3.77 fold increase in the hazard of death and to shorter overall survival (OS) (p<.001). Multivariate analysis selected NOTCH1 mutations as an independent predictor of OS after controlling for confounding clinical and biological variables. The independent prognostic value of NOTCH1 mutations was externally confirmed in the validation series. The poor prognosis conferred by NOTCH1 mutations was attributable, at least in part, to shorter treatment-free survival and higher risk of Richter transformation. Although NOTCH1 mutated patients were devoid of TP53 disruption in >90% cases in both training and validation series, the OS predicted by NOTCH1 mutations was similar to that of TP53 mutated/deleted CLL. NOTCH1 mutations are an independent predictor of CLL OS, tend to be mutually exclusive with TP53 abnormalities and identify cases with a dismal prognosis. [ABSTRACT FROM AUTHOR]

Although the heterogeneity of wood could preclude assessment of the performances of adhesion, the within-tree variations in its thermodynamic properties still remain unexplored. This study analyzed the surface free energy of wood ( γ) calculated by the geometric mean approach along the radius and at different sampling heights in black spruce and balsam fir with a statistical model, employing apparent contact angles of three testing liquids. Sampling height and species affected the apparent contact angles, and consequently the polar ( $$ \gamma_{W}^{P} $$) and dispersed ( $$ \gamma_{W}^{D} $$) components of γ, but no significant difference was observed along the radius. On average, γ was 43.77 mJ m at the stem base and gradually decreased, attaining 27.19 mJ m at 14 m of height. $$ \gamma_{W}^{P} $$ was markedly higher than $$ \gamma_{W}^{D} $$ with an opposite pattern along the tree height. These findings demonstrated the huge variability in γ along the stem, which could be related to the structural or chemical features of wood. [ABSTRACT FROM AUTHOR]

The genetic lesions identified in chronic lymphocytic leukemia (CLL) do not entirely recapitulate the disease pathogenesis and the development of serious complications, such as chemorefractoriness. While investigating the coding genome of fludarabine-refractory CLL, we observed that mutations of SF3B1, encoding a splicing factor and representing a critical component of the cell spliceosome, were recurrent in 10 of 59 (17%) fludarabine-refractory cases, with a frequency significantly greater than that observed in a consecutive CLL cohort sampled at diagnosis (17/301, 5%; P = .002). Mutations were somatically acquired, were generally represented by missense nucleotide changes, clustered in selected HEAT repeats of the SF3B1 protein, recurrently targeted 3 hotspots (codons 662, 666, and 700), and were predictive of a poor prognosis. In fludarabine-refractory CLL, SF3B1 mutations and TP53 disruption distributed in a mutually exclusive fashion (P = .046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL. [ABSTRACT FROM AUTHOR]

Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types that remain orphan of molecular lesions in cancer-related genes. Detection of active NF-κB signaling in 14 (58%) of 24 SMZLs prompted the investigation of NF-κB molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-κB genes occurred in 36 (36%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-κB pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-κB in SMZL. BIRC3 inactivation in SMZL recurred because of somatic mutations that disrupted the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18) translocation, which points to BIRC3 disruption as a common mechanism across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-κB provide a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a suitable target for NF-κB therapeutic approaches in this lymphoma. [ABSTRACT FROM AUTHOR]

The article presents a study to determine whether serum beta-2 microglobulin (B2M) levels predict progression to symptomatic multiple myeloma (MM), and the way B2M interacts with predictors of progression to symptomatic MM. It explores the cumulative probability of progression to symptomatic MM as the primary end point among 148 patients with asymptomatic MM. The result shows that B2M is an independent predictor when combined with most prognosticators of asymptomatic MM progression.

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic monoclonal expansion of <5·0 × 109/l circulating CLL-phenotype B-cells. The relationship between MBL and Rai 0 CLL, as well as the impact of biological risk factors on MBL prognosis, are unknown. Out of 460 B-cell expansions with CLL-phenotype, 123 clinical MBL (cMBL) were compared to 154 Rai 0 CLL according to clinical and biological profile and outcome. cMBL had better humoral immune capacity and lower infection risk, lower prevalence of del11q22-q23/del17p13 and TP53 mutations, slower lymphocyte doubling time, and longer treatment-free survival. Also, cMBL diagnosis was a protective factor for treatment risk. Despite these favourable features, all cMBL were projected to progress, and lymphocytes <1·2 × 109/l and >3·7 × 109/l were the best thresholds predicting the lowest and highest risk of progression to CLL. Although IGHV status, CD38 and CD49d expression, and fluorescence in situ hybridization (FISH) karyotype individually predicted treatment-free survival, multivariate analysis identified the presence of +12 or del17p13 as the sole independent predictor of treatment requirement in cMBL (Hazard ratio: 5·39, 95% confidence interval 1·98–14·44, P = 0·001). Overall, these data showed that cMBL has a more favourable clinical course than Rai 0 CLL. Given that the biological profile can predict treatment requirement, stratification based on biological prognosticators may be helpful for cMBL management. [ABSTRACT FROM AUTHOR]

Recent guidelines emphasise the risk of hepatitis B virus (HBV) reactivation among patients with hematologic malignancies of B lineage, in which HBV has been recently hypothesised to play a pathogenetic role. We aimed to determine the prevalence of occult HBV infection (OBI) of peripheral blood mononuclear cells, defined as detection of sequences from ≥2 HBV genes in subjects lacking hepatitis B surface antigen, among patients with treatment-naive chronic lymphocytic leukemia (CLL). HBV DNA sequences from four HBV genes (S, X, core and pol) were searched for in archival material obtained at diagnosis (N = 173), and from age and sex-matched controls. OBI was observed in 17/173 (10%) patients and 5/173 (3%) controls (OR = 3.6, 95% CI 1.37-9.79, p = 0.014). OBI was not associated with differences on 5-year survival and biological predictors, but patients with CLL with OBI had significantly lower peripheral blood lymphocyte count. After 8 years of observation without treatment, one OBI positive patient with CLL converted into positive HBsAg serology and developed active hepatitis. In conclusion, OBI is significantly more prevalent among patients with CLL than in age and sex-matched controls, and may contribute to the susceptibility of patients with CLL to HBV reactivation, whether exposed or not to biological agents. [ABSTRACT FROM AUTHOR]

Predictors of chronic lymphocytic leukaemia (CLL) transformation to Richter syndrome (RS) are not established and were investigated in 185 consecutive CLL cases. Actuarial incidence of RS ( n = 17; all diffuse large B-cell lymphomas) at 10 years was 16·2% (95% confidence interval: 8·0–24·4%). At CLL diagnosis, prognosticators of RS by univariate analysis were IGHV homology ≥98% ( P = 0·006), IGHV4-39 usage ( P < 0·001), del13q14 absence ( P = 0·004), expression of CD38 ( P < 0·001) and ZAP70 ( P = 0·004), size ( P < 0·001) and number ( P < 0·001) of lymph nodes, advanced Binet stage ( P = 0·002), and lactate dehydrogenase ( P < 0·001). Multivariate analysis, performed separately for biological and clinical variables, identified CD38 expression [Hazard ratio (HR) = 4·26; P = 0·018], IGHV4-39 usage (HR = 4·29; P = 0·018), and lymph node size ≥3 cm (HR = 9·07; P < 0·001) as independent RS prognosticators. A multivariate model simultaneously analysing biological and clinical variables identified lymph node size ≥3 cm (HR = 6·51; P = 0·001) and del13q14 absence (HR = 4·08; P = 0·031) as independent RS prognosticators. Risk factors of CLL transformation differed from risk factors of CLL progression. These results suggest that CD38 and del13q14 may identify biological subsets of CLL with different RS predisposition. Predominant nodal disease, CD38 expression, IGHV4-39 usage, and absence of del13q14 may help in predicting RS at CLL diagnosis. Close monitoring and a careful biopsy policy are needed in patients carrying transformation risk factors. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow necrosis is a rare cause of bone marrow failure. Malignancy is the most frequent cause of bone marrow necrosis. Among malignancies, non-Hodgkin lymphoma (NHL) accounts for 10% of cases of bone marrow necrosis. Virtually all reported cases of NHL-associated bone marrow necrosis have developed in immunocompetent hosts. We report on a case of bone marrow necrosis complicating post-transplant lymphoproliferative disorder (PTLD) and resolving after rituximab monotherapy. This case report provides the first evidence of (i) bone marrow necrosis as a complication of PTLD; (ii) rapid resolution of NHL-associated bone marrow necrosis after rituximab treatment. [Copyright &y& Elsevier]

Monoclonal gammopathy of uncertain significance (MGUS) may become symptomatic for autoimmune manifestations. We report on the prevalence and clinical course of immune thrombocytopenic purpura (ITP) observed in a consecutive series of 228 MGUS patients. At MGUS diagnosis, ITP was determined in 6/228 cases, accounting for a prevalence of 2630/100 000 [95% confidence interval (CI): 1210–5620]. One incidental ITP case occurred after 21 months of follow-up. After a follow-up of 681·3 patient-years, the crude incidence of ITP in MGUS was 146·8 per 100 000 patient-year (95% CI: 3·7–817·8). Overall, these observations point to an association between MGUS and ITP. [ABSTRACT FROM AUTHOR]

Abstract: Hairy cell leukaemia (HCL) occasionally displays a monoclonal gammopathy, yet the association of HCL with paraproteinemic demyelinating neuropathy (PDN) has not been reported. We describe a HCL case complicated by PDN and high titers of monoclonal IgM against myelin associated glycoprotein (MAG). Heavy and light chains of the patient''s anti-MAG monoclonal protein were consistent with those expressed by HCL cells. After treatment with cladribrine, remission of HCL strictly paralleled disappearance of the IgM monoclonal protein and of the serum anti-MAG activity, and led to PDN clinical and electrophysiological improvement. Purine analogs may represent a choice in IgM PDN associated with lymphoproliferative disorders. [Copyright &y& Elsevier]

Abstract: Idiopathic erythrocytosis (IE) is a primary erythrocytosis not fulfilling the criteria for polycythemia vera (PV) diagnosis. In order to verify the relationship between IE and PV, we screened JAK2V617F mutation in a consecutive series of 11 IE and, for comparison, in 15 PV. JAK2V617F mutation was screened by both cDNA sequencing and mutation specific PCR in both peripheral blood and bone marrow samples. All 11 IE tested negative for JAK2V617F mutation, which, conversely, occurred in 11/15 (73.3%) PV. Our results demonstrate that JAK2V617F is absent in IE and may represent a useful molecular marker for distinguishing IE from PV. [Copyright &y& Elsevier]

Aberrant promoter hypermethylation is a mechanism of tumour suppressor gene inactivation. We explored aberrant promoter hypermethylation of multiple genes in 88 human immunodeficiency virus (HIV)-non Hodgkin lymphomas (NHL), 25 post-transplant lymphoproliferative disorders (PTLD) and five common variable immunodeficiency (CVI)-related NHL. Twenty-six of 79 (32·9%) HIV-NHL, eight of 14 (57·1%) PTLD and two of five (40·0%) CVI–NHL showed aberrant hypermethylation of O6-methylguanine-DNA methyltransferase ( MGMT). Aberrant hypermethylation of death-associated protein-kinase ( DAP-K) occurred in 70 of 84 (83·3%) HIV–NHL, 19 of 25 (72·0%) PTLD and three of five (60·0%) CVI–NHL. These data implicate MGMT and DAP-K hypermethylation in lymphomagenesis of immunodeficient hosts. In particular, promoter hypermethylation of DAP-K represents the most frequent molecular alteration yet identified in immunodeficiency-related lymphomas. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 40% of all B-cell non-Hodgkin lymphomas of the Western world. According to the "WHO classification of tumours of the haematopoietic and lymphoid tissues", the term DLBCL is likely to include more than one disease entity, as suggested by the marked variability of the clinical presentation and response to treatment of this disease. Such heterogeneity may reflect the occurrence of distinct molecular subtypes of DLBCL as well as differences in the host's immune function. In immunocompetent hosts, approximately 50% DLBCL carry one of two primary molecular lesions defining two distinct genotypic subgroups, characterized by activation of either the BCL-6 or the BCL-2 proto-oncogene. Conversely, the remaining DLBCL of immunocompetent hosts display one of several molecular lesions, each associated with a small subset of cases and including activation of the proto-oncogenes REL , MUC-1 , BCL-8 and c-MYC . The molecular pathogenesis of immunodeficiency-associated DLBCL differs substantially from that of DLBCL in immunocompetent hosts. In fact, EBV infection is present in a large fraction of immunodeficiency-associated DLBCL, whereas it is consistently negative in DLBCL of immunocompetent hosts, probably reflecting the critical role of disruption of the immune system in this disease. Finally, the application of DNA microarray technology to DLBCL has led to the distinction of two disease variants: a germinal center like DLBCL and an activated peripheral B-cell like DLBCL. Overall the molecular features of DLBCL may identify prognostic categories of the disease and may represent a powerful tool for therapeutic stratification. [ABSTRACT FROM AUTHOR]

Background: Neurophysiological studies recognized that Autism Spectrum Disorder (ASD) is associated with altered patterns of over- and under-connectivity. However, little is known about network organization in children with ASD in the early phases of development and its correlation with the severity of core autistic features. Methods: The present study aimed at investigating the association between brain connectivity derived from MEG signals and severity of ASD traits measured with different diagnostic clinical scales, in a sample of 16 children with ASD aged 2 to 6 years. Results: A significant correlation emerged between connectivity strength in cortical brain areas implicated in several resting state networks (Default mode, Central executive, Salience, Visual and Sensorimotor) and the severity of communication anomalies, social interaction problems, social affect problems, and repetitive behaviors. Seed analysis revealed that this pattern of correlation was mainly caused by global rather than local effects. Conclusions: The present evidence suggests that altered connectivity strength in several resting state networks is related to clinical features and may contribute to neurofunctional correlates of ASD. Future studies implementing the same method on a wider and stratified sample may further support functional connectivity as a possible biomarker of the condition. [ABSTRACT FROM AUTHOR]

The article focuses on the study by J. A. Woyach and colleagues which perceives the prolonged lymphocytosis as a failure of chronic lymphocytic leukemia (CLL) treatment with ibrutinib. It mentions that the proof of principle that quiescent leukemic cells are composing the prolonged lymphocytosis produced by ibrutinib is provided by the study. It adds that 20% of the CLL cases responding to ibrutinib were also identified by the authors.

The article discusses chronic lymphocytic leukemia (CLL) in patients with BCL3 translocation. It mentions that BCL3 translocation occurs as a consequence of genetic lesion along with Hodgkin lymphoma, chronic B-cell lymphoproliferative disorders and CLL. It further offers information on a case study involving several patients in order to study BCL3 translocation occurring from CLL.