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Summary: We describe the clinical phenotype, management strategies and outcomes of 22 patients with autoimmune myelofibrosis (AIMF); median age: 45 years; 77% females; 83% with autoimmune disease, pancytopenia in 32% and transfusion‐requiring anaemia in 59%. All informative cases were negative for JAK2 (n = 18) and CALR/MPL mutations (n = 12). Fourteen of nineteen (74%) evaluable patients achieved complete response (CR) based on the resolution of cytopenias. First‐line treatments included steroids +/− immunosuppressive agents, cyclosporin and mycophenolate with CR in 7 of 13 (54%), 1 of 2 (50%) and 1 of 2 (50%) respectively. Rituximab salvage therapy yielded CR in 4 of 5 (80%) cases. The current study provides information on steroid‐sparing treatments for AIMF. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate if the operated knee environment remains abnormal in patients successfully treated with anterior cruciate ligament reconstruction (ACL‐R). Methods: Thirty asymptomatic patients were enrolled (28 men, 2 women, age 28.6 ± 6.54 years, body mass index: 24.9 ± 3.0 kg/m2) and evaluated at 42.2 ± 12.5 months after surgery. Patients were assessed with patient‐reported outcome measurements and with a triaxial accelerometer. The temperature of the knees as well as four regions of interest were evaluated with an infrared thermographic camera FLIR T1020 (FLIR® Systems) according to a standardised protocol including a baseline evaluation and further evaluations immediately after exercise and after 5, 10 and 20 min. The temperature of the ACL‐R knee was compared to that of the contralateral healthy knee for the purpose of the study. Results: The mean temperature of the knee was higher (p = 0.010) for the ACL‐R knees (31.4 ± 1.4°C) compared to the healthy knees (31.1 ± 1.6°C), as well as for the patellar area (p = 0.005), the lateral area (p = 0.016) and the medial area (p = 0.014). The analysis of the response to the exercises of the ACL‐R knees showed similar trends to the healthy knees but higher temperature values at all time points (p < 0.05). Patients who underwent ACL‐R with concomitant meniscal treatment showed higher knee temperatures compared to ACL‐R knees without concomitant meniscal treatment after 5 (p = 0.047), 10 (p = 0.027) and 20 min (p = 0.048). Conclusions: The temperature of asymptomatic knees previously treated with ACL‐R is higher than the contralateral healthy knee, both at rest and after exercise, with a further increase in knees that underwent both ACL‐R and meniscal treatment. These results suggest an inflammatory state persisting years after the surgery, which could predispose to the early onset of knee degeneration. Level of Evidence: III, Case–control study. [ABSTRACT FROM AUTHOR]

Summary: Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy‐related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10‐year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia‐free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision‐making in MDS‐del(5q) regarding allogeneic stem cell transplant. [ABSTRACT FROM AUTHOR]

Pulsed thermography has been applied to the quantitative characterization of the insertions of two ancient bronzes, the Boxer at Rest and the Hellenistic Prince. The analysis of the thermographic signal time dependence performed by a specifically developed model enabled the evaluation of the insertions' thickness and of elements which could provide indications about the procedure followed for their insertion. This could be achieved by exploiting a semi‐empirical relation establishing the thermal diffusivity dependence on the total effective weighted concentration of Sn and Pb atoms obtained from the analysis of the values determined on samples containing different concentrations of Sn and Pb. [ABSTRACT FROM AUTHOR]

This article discusses the use of the drug Bortezomib in the treatment of primary effusion lymphoma (PEL), a type of non-Hodgkin B cell lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV). The current standard chemotherapy for PEL only provides partial remission in a small percentage of patients. Bortezomib has shown cytotoxic effects against PEL cells in vitro and in mice, prolonging survival and preventing ascites formation. The study also explores the potential of combining Bortezomib with Chloroquine, but the results show a reduction in the therapeutic effect. The findings provide new insights into the mechanisms of Bortezomib and highlight the importance of understanding these mechanisms to improve treatment outcomes for PEL. [Extracted from the article]

Summary: Bone marrow (BM) studies are pivotal for the diagnosis of haematological disorders. Their introduction into clinical haematology dates back to the work of Giovanni Ghedini (1877–1959), an Italian physician who first conceived BM sampling in 1908. Ghedini's proposal stemmed from his clinical experience and from the scientific developments that characterised his epoch. By presenting selected passages of Ghedini's publications, this report considers the theoretical and historical bases of his work and analyses its practical implications for modern haematology. [ABSTRACT FROM AUTHOR]

In this work, the application of nanodiamond (ND)‐composites and dispersions as consolidating agents for parchment substrates has been studied. Different nanocomposites and ND‐based dispersions have been tested showing very promising results and making ND a potential high‐performance additive in the field of restoration. The effect of ND treatment on parchment has been evaluated by analyzing the variations in the parchment denaturation temperature, with respect to the untreated samples, by means of the Light Transmission Analysis (LTA), before and after artificial aging. The hydrolysis/gelatinization degree of the collagen molecule has also been analyzed by means of the Attenuated Total Reflection Fourier Transform IR (FTIR‐ATR) spectroscopy on the same samples investigated by LTA. ND composites, at certain concentrations, seem to improve the structural stability of the collagen networking, contrasting the thermo‐hygrometrically induced aging. Therefore, ND has confirmed to be a promising material to be applied for the restoration and conservation of Cultural Heritage. [ABSTRACT FROM AUTHOR]

Cesium lead halide perovskite nanocrystals (NCs) have gained enormous attention as promising light‐emitting and light‐converting materials. Most of their applications require embedding NCs in various matrices, which is a challenging task due to their low stability, especially in the case of red‐emitting CsPbI3 NCs. In this work, a new approach is proposed allowing the formation of red‐emitting perovskite NCs by anion exchange induced directly inside a solid polymer matrix using green‐emitting CsPbBr3 NCs as templates and iodododecane as an iodine source. Moreover, a simple and efficient route to photo‐assisted termination of the anion exchange reaction in the polymer composite after reaching desired optical properties is demonstrated. The findings allow the authors to pattern a thin composite film with an ultrashort UV laser resulting in a selective generation of green‐ and red‐emitting features with a 15 µm resolution. [ABSTRACT FROM AUTHOR]

This paper presents a study carried out on the painted altarpiece preserved inside the Basilica of Santa Maria in Cosmedin, Rome, by combining three imaging techniques operating in the near‐ and mid‐infrared spectral ranges. The altarpiece has several pictorial layers and restorations, which have superimposed over time for stylistic adjustment and conservative purposes up to its present appearance. The results obtained in this study enable the detection of damage to the wooden support and the identification of pictorial features buried beneath the visible paint layer, thus providing significant information on the historical and artistic characterization of the artefact. [ABSTRACT FROM AUTHOR]

Statins are inhibitors of the mevalonate pathway that besides being cholesterol lowering agents, display anti‐cancer properties. This is because cholesterol is an essential component of cell membranes but also because the mevalonate pathway controls protein farnesylation and geranylation, processes essential for the activity of GTPase family proteins. In this study, we found that Lovastatin exerted a dose‐ and time‐dependent cytotoxic effect against PEL cells, an aggressive B cell lymphoma strictly associated with the gammaherpesvirus KSHV and characterized by a poor response to conventional chemotherapies. At molecular level, Lovastatin by dephosphorylating STAT3, induced ERK1/2 activation that inhibited autophagy and phosphorylated p53ser15 that in turn maintained ERK1/2 activated and up‐regulated p21. However, p21 played a pro‐survival role in this setting, as its inhibition by UC2288 further reduced cell survival in PEL cells undergoing Lovastatin treatment. In conclusion, this study suggests that Lovastatin may represent a valid therapeutic alternative against PEL cells, especially if used in combination with p21 inhibitors. [ABSTRACT FROM AUTHOR]

Background: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population‐based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. Methods: Data from the Texas Cancer Registry (1995‐2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non‐Hispanic) and geographic location (border vs non‐border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel‐Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. Results: Hispanic patients were diagnosed at a younger age than non‐Hispanic patients and presented with increased comorbidities. Whereas non‐Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79‐2.08; P <.001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07‐1.51; P =.02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04‐1.33; P =.0009) compared with Hispanics living elsewhere in Texas. Conclusions: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities. Hispanic patients with blood cancer are diagnosed at a younger age, have poor presentation, and have worse prognoses compared with non‐Hispanic patients. Hispanics with acute lymphocytic leukemia, acute myeloid leukemia, or chronic myelogenous leukemia who are diagnosed near the Texas/Chihuahua border have worse outcomes compared with Hispanics living elsewhere. [ABSTRACT FROM AUTHOR]

Although primary pancreatic lymphoma is a rare cause of pancreatic mass, this diagnosis should be considered during work‐up. Furthermore, when adequate diagnostic material is available from biopsy, complete workup of the lymphoma, including not only type but also subtype when applicable, should be performed. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged ≥ 2 months in the United States, and is currently under Health Authority review in the EU. Methods: Subjects included patients with SMA aged 2 months–60 years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age‐appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD‐OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2–6 months depending on study and assessment. SD‐OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study. Results: A total of 245 patients receiving risdiplam were assessed. Comprehensive, high‐quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD‐OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam‐induced toxicity and resolved with ongoing treatment. Interpretation: Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam. [ABSTRACT FROM AUTHOR]

A major challenge in regenerative medicine is replacing cells lost through injury or disease. While significant progress has been made, much remains unknown about the accuracy of native regenerative programs in cell replacement. Here, we capitalized on the regenerative capacity and stereotypic retinal organization of zebrafish to determine the specificity with which retinal Müller glial cells replace lost neuronal cell types. By utilizing a targeted genetic ablation technique, we restricted death to all or to distinct cone photoreceptor types (red, blue, or UV‐sensitive cones), enabling us to compare the composition of cones that are regenerated. We found that Müller glia produce cones of all types upon nondiscriminate ablation of these photoreceptors, or upon selective ablation of red or UV cones. Pan‐ablation of cones led to regeneration of the various cone types in relative abundances that resembled those of nonablated controls, that is, red > green > UV ~ blue cones. Moreover, selective loss of red or UV cones biased production toward the cone type that was ablated. In contrast, ablation of blue cones alone largely failed to induce cone production at all, although it did induce cell division in Müller glia. The failure to produce cones upon selective elimination of blue cones may be due to their low abundance compared to other cone types. Alternatively, it may be that blue cone death alone does not trigger a change in progenitor competency to support cone genesis. Our findings add to the growing notion that cell replacement during regeneration does not perfectly mimic programs of cell generation during development. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy represents a major hurdle to successful cancer treatment. A key role for efficient response to anticancer therapies is played by TP53 oncosuppressor gene that indeed is mutated in 50% of human cancers or inactivated at protein level in the remaining 50%. Homeodomain‐interacting protein kinase 2 (HIPK2) is the wild‐type p53 (wtp53) apoptotic activator, and its inhibition by hypoxia or hyperglycemia may contribute to tumor chemoresistance mainly by impairing p53 apoptotic activity. Another important molecule able to induce chemoresistance is nuclear factor erythroid 2 (NF‐E2) p45‐related factor 2 (NRF2) transcription factor, whose activation by oxidative and/or electrophilic stress regulates a transcriptional antioxidant program allowing cancer cells to adapt and survive to stresses. NRF2 may shift from cytoprotective to tumor‐promoting function, according to tumor phases. NRF2 may crosstalk with both wtp53 and mutant p53 (mutp53), inhibiting the wtp53 apoptotic function and strengthening the mutp53 oncogenic function. NRF2 has also been shown to induce HIPK2 mRNA expression cooperating in inducing cytoprotection. Although HIPK2, p53, and NRF2 have been individually extensively studied, their interplay has not been clearly addressed yet. On the basis of the background and our results, we aim at hypothesizing the unexpected pro‐survival activity played by the NRF2/HIPK2/p53 interplay that can be hijacked by cancer cells to bypass drugs cytotoxicity. [ABSTRACT FROM AUTHOR]

Enumeration of blasts and promonocytes is essential for World Health Organization (WHO) classification of myelomonocytic neoplasms. The accuracy of distinguishing blasts, promonocytes and monocytes, including normal vs abnormal monocytes, remains controversial. The objective of this analysis is to assess concordances between experienced hematopathologists in classifying cells as blasts, promonocytes, and monocytes according to WHO criteria. Each of 11 hematopathologists assessed glass slides from 20 patients [12 with chronic myelomonocytic leukemia (CMML) and 8 with acute myeloid leukemia (AML)] including blood and BM aspirate smears, and limited nonspecific esterase (NSE) stains. All cases were blindly reviewed. Fleiss' extension of Cohen's kappa for multiple raters was used on these variables, separately for peripheral blood (PB) and bone marrow (BM). Spearman's rank correlation was used to assess correlations between each pair of hematopathologists for each measurement. For the classification based on the sum of blasts and promonocytes in the BM, Fleiss' kappa was estimated as 0.744. For PB, categorizing patients according to the sum of blasts and promonocytes, Fleiss' kappa was estimated as 0.949. Distinction of abnormal monocytes from normal monocytes in PB did not achieve a good concordance and showed strong evidence of differences between hematopathologists (P <.0001). The hematopathologists achieved a good concordance rate of 74% in CMML vs AML classification and a high k rate, confirming that criteria for defining the blasts equivalents (blasts plus promonocytes) could be applied consistently. Identification of monocyte subtypes (abnormal vs normal) was not concordant. Our results support the practice of combining blasts/promonocytes into a single category. [ABSTRACT FROM AUTHOR]

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of "overlapping" myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing "dysplastic" features and others a predominant "proliferative" phenotype. Accounting for this diversity, two variants of CMML are recognized: "dysplastic" CMML defined by WBC < 13 × 109/L and "proliferative" CMML with WBC ≥ 13 × 109/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the "oligomonocytic" variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 109/L. It can be considered a "pre‐phase," as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new "CMML‐0" category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML. [ABSTRACT FROM AUTHOR]

The ultraviolet (UV) component of solar radiation is the driving force of life on earth, but it can cause photoaging and skin cancer. In this study, we investigated the effects of the glucosamine‐derivative 2‐(N‐Acetyl)‐L‐phenylalanylamido‐2‐deoxy‐β‐D‐glucose (NAPA) on human primary fibroblasts (FBs) stimulated in vitro with environmental levels of UVB radiation. FBs were irradiated with 0.04 J cm−2 UVB dose, which resulted a mild dosage as shown by the cell viability and ROS production measurement. This environmental UVB dose induced activation of MAP kinase ERK 1/2, the stimulation of c‐fos and at lower extent of c‐jun, and in turn AP‐1‐dependent up‐regulation of pro‐inflammatory factors IL‐6 and IL‐8 and suppression of collagen type I expression. On the contrary, 0.04 J cm−2 UVB dose was not able to stimulate metalloprotease production. NAPA treatment was able to suppress the up‐regulation of IL‐6 and IL‐8 via the inhibition of MAP kinase ERK phosphorylation and the following AP‐1 activation, and was able to attenuate the collagen type I down‐regulation induced by the UVBs. Taken together, our results show that NAPA, considering its dual action on suppression of inflammation and stimulation of collagen type I production, represents an interesting candidate as a new photoprotective and photorepairing agents. [ABSTRACT FROM AUTHOR]

The dialogue between cancer cells and the surrounding fibroblasts, tumor‐associated macrophages (TAM), and immune cells can create a tumor microenvironment (TME) able to promote tumor progression and metastasis and induce resistance to anticancer therapies. Cancer cells, by producing growth factors and cytokines, can recruit and activate fibroblasts in the TME inducing their transdifferention in cancer‐associated fibroblasts (CAFs). Then, CAFs, in a reciprocal cross‐talk with cancer cells, sustain cancer growth and survival and support malignancy and tumor resistance to therapies. Therefore, the identification of the molecular mechanisms regulating the interplay between cancer cells and fibroblasts can offer an intriguing opportunity for novel diagnostic and therapeutic anticancer purpose. HIPK2 is a multifunctional tumor suppressor protein that modulates cancer cell growth and apoptosis in response to anticancer drugs and negatively regulates pathways involved in tumor progression and chemoresistance. HIPK2 protein downregulation is induced by hypoxia and hyperglycemia and HIPK2 knockdown favors tumor progression and resistance to therapy other than a pseudohypoxic, inflammatory, and angiogenic cancer phenotype. Therefore, we hypothesized that HIPK2 modulation in cancer cells could contribute to modify the tumor–host interaction. In support of our hypothesis, here we provide evidence that culturing human fibroblasts (hFB) with conditioned media derived from cancer cells undergoing HIPK2 knockdown (CMsiHIPK2) triggered their transdifferentiation CAF‐like, compared to hFB cultured with CM‐derived from HIPK2‐carrying control cancer cells. CAF transdifferentiation was identified by expression of several markers including α‐smooth muscle actin (α‐SMA) and collagen I and correlated with autophagy–mediated caveolin‐1 degradation. Although the molecular mechanisms dictating CAF‐transdifferentiation need to be elucidated, these results open the way to further study the role of HIPK2 in TME remodeling for prognostic and therapeutic purpose. [ABSTRACT FROM AUTHOR]

Within a general volcanic unrest in the densely urbanized area of Campi Flegrei caldera (Italy) an increase in the activity of Pisciarelli hydrothermal area is occurring. The seismic amplitude of Pisciarelli fumarolic tremor is a proxy for the fluid emission rate of the entire Solfatara‐Pisciarelli hydrothermal system. The long‐term analysis indicates a significant increase, by a factor of ~3 of the fumarolic tremor amplitude since May 2017. This increment matches with the trend of geochemical and seismic parameters observed in Campi Flegrei, therefore highlighting that Pisciarelli is a key site to monitor the volcanic unrest underway in this high‐risk caldera. The analysis of data from three closely spaced seismic stations provided new clues about the source mechanism of the tremor. Analyzing the fumarolic tremor amplitude we could also identify an episode of enlargement of the emission area close to the main fumarole of Pisciarelli. We propose a monitoring system based on the fumarolic tremor analysis, which provides real‐time information on the Pisciarelli hydrothermal activity and therefore on the current unrest in Campi Flegrei caldera. Key Points: Fumarolic tremor indicates a new increase of the Pisciarelli hydrothermal activity linked to the current large‐scale unrest at Campi FlegreiThe fumarolic tremor analysis allowed us to identify an episode of enlargement of Pisciarelli mud emissionsWe propose a method for monitoring the hydrothermal system based on proximal measurements of fumarolic tremor [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the morphological and surface roughness changes in dental root samples following periodontal scaling by hand curette, piezoelectric ultrasonic devices or a combination of these. Methods: Twenty‐four monoradicular teeth extracted as a result of periodontal disease were divided into 4 groups: Group A was treated by piezoelectric ultrasonic scaler Piezon® Master 400; Group P by piezoelectric ultrasonic scaler PiezoSmart®; Group C using Gracey curette 7/8; Group AC by a combined technique of piezoelectric ultrasonic scaler Piezon® Master 400 and Gracey curette 7/8. The treated samples were then analysed using a white light interferometer and scanning electron microscopy (SEM). Results: Roughness analysis revealed major surface alterations in Group C (Sa = 24.98 μm); the samples treated using the combined technique (Group AC) showed reduced but still significant alteration (Sa = 14.48 μm), while samples treated with the piezoelectric ultrasonic devices (Group A and Group P) presented the lowest roughness values (Sa = 8.99 and Sa = 4.45 μm, respectively). A significant difference was found between groups C and P (P = 0.036). SEM analysis confirmed the roughness analysis revealing non‐homogeneous surfaces in Group C, while a less morphological alteration was noted in the other groups. Conclusion: All periodontal devices used in this in vitro study produced a certain degree of surface alteration. Hand curettes appear to have a major impact on surface integrity compared with piezoelectric ultrasonic devices. [ABSTRACT FROM AUTHOR]

Summary: The JAK2 V617F mutation is characteristic of most Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs) and occurs rarely in de novo acute myeloid leukaemia (AML). We sought to characterize AMLs that harbour this mutation and distinguish those that arise de novo (AML‐DN) from those that reflect transformation of an underlying MPN (AML‐MPN). Forty‐five patients with JAK2 V617F‐mutated AML were identified; 15 were AML‐DN and 30 were AML‐MPN. AML‐MPN cases were more likely to have splenomegaly (P = 0·02), MPN‐like megakaryocytes and higher mean JAK2 V617F VAF at diagnosis (P = 0·04). Mutations involving TET2 were exclusively identified in AML‐DN patients. Mutations of genes affecting DNA methylation were more common in AML‐DN (P < 0·01). A complex karyotype was more frequent in AML‐MPN cases than in AML‐DN (P < 0·01), with AML‐DN more likely to display a normal karyotype (P = 0·02). Bone marrow histology after recovery from induction chemotherapy in AML‐DN cases revealed no morphological evidence of any previously occult MPNs, while this was evident in most of the AML‐MPN specimens (P < 0·01). These findings in this largest study of JAK2 V617F‐mutated AMLs indicate that AML‐DN is distinct from AML‐MPN. [ABSTRACT FROM AUTHOR]

Background: Although recombinant interferon-α (rIFNα) effectively treats patients with early myelofibrosis, the effect of driver and high molecular risk (HMR) mutations has not been considered. In this phase 2 study, for the first time, the authors correlate response to rIFNα treatment with driver and HMR mutations.Methods: Patients were diagnosed using World Health Organization or International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria. Only patients who had low or intermediate-1 Dynamic International Prognostic Scoring System scores with ≥15% hematopoietic bone marrow foci were included. History, symptom assessment, physical examination, and blood and bone marrow studies were performed. Genomic DNA was extracted from frozen cells, and next-generation targeted sequencing of 45 genes was performed. Either rIFNα-2b (0.5 million units subcutaneously 3 times weekly) or pegylated rIFNα-2a (45 μg weekly) with escalation was initiated. All patients were followed at the authors' institution, and regular bone marrow biopsies were encouraged. International Working Group for Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet treatment response criteria were used.Results: Of 30 patients (16 women and 14 men; median age, 58 years), 22 were classified as low risk, and 8 were classified as intermediate-1 risk. Two patients achieved complete remission, 9 achieved partial remission, 4 had clinical improvement, 7 had stable disease; 3 had progressive disease, 1 relapsed, and 4 died. There were 22 patients with JAK mutations, 6 with CALR mutations, and 2 with MPL mutations. Seventy-three percent of patients improved or remained stable with acceptable toxicity, including 37% who achieved complete or partial remission. There was no correlation between treatment response and baseline driver mutations or Dynamic International Prognostic Scoring System scores. Of 8 poor responders, 3 had ASXL1 or SRSF2 mutations.Conclusions: Early treatment with rIFNα in patients without HMR mutations may prevent the development of marked splenomegaly, anemia, and florid myelofibrosis. Molecular profiling at the time of diagnosis may predict prognosis and treatment response. Cancer 2017;123:2680-87. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

In this study, the dual-reverse-arrow fractal (DRAF) geometry is applied to the sides of a slotted microstrip triangular patch to design ultra-wideband (UWB) antenna with a coplanar waveguide (CPW) feed with and without notch bands. It is shown that the proposed DRAF geometry has the capability of both reducing the antenna size, but without decreasing its bandwidth and also maintaining the other antenna radiation characteristics. It is shown that the antenna is miniaturised by 40% compared with the simple triangular patch. Furthermore, in order to prevent any interference of the proposed antenna with the wireless system of high performance radio LAN (HiperLAN)/2, a notch band is created by cutting two similar slots in the Tshaped CPW-feed. Such an antenna has applications in UWB systems. Two prototype DRAF antennas are fabricated and measured, which verify its desirable features. [ABSTRACT FROM AUTHOR]

Ataxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated ( ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A-T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione ( GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6-phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity. [ABSTRACT FROM AUTHOR]

Small B cell lymphoid neoplasms are the most common lymphoproliferative disorders involving peripheral blood ( PB) and bone marrow ( BM). The Bone Marrow Workshop ( BMW) organized by the European Bone Marrow Working Group ( EBMWG) of the European Association for Haematopathology ( EAHP) during the XVIIth EAHP Meeting in Istanbul, October 2014, was dedicated to discussion of cases illustrating how the recent advances in immunophenotyping, molecular techniques and cytogenetics provide better understanding and classification of these entities. Submitted cases were grouped into following categories: (i) cases illustrating diagnostic difficulties in chronic lymphocytic leukaemia (CLL); (ii) cases of BM manifestations of small B cell lymphoid neoplasms other than CLL; (iii) transformation of small B cell lymphoid neoplasms in the BM; and (iv) multiclonality and composite lymphomas in the BM. This report summarizes presented cases and conclusions of the BMW and provides practical recommendations for classification of the BM manifestations of small B cell lymphoid neoplasms based on the current state of knowledge. [ABSTRACT FROM AUTHOR]

Stellar models provide a vital basis for many aspects of astronomy and astro-physics. Recent advances in observational astronomy - through asteroseismology, precision photometry, high-resolution spectroscopy, and large-scale surveys - are placing stellar models under greater quantitative scrutiny than ever. The model limitations are being exposed and the next generation of stellar models is needed as soon as possible. The current uncertainties in the models propagate to the later phases of stellar evolution, hindering our understanding of stellar populations and chemical evolution. Here we give a brief overview of the evolution, importance, and substantial uncertainties of core helium burning stars in particular and then briefly discuss a range of methods, both theoretical and observational, that we are using to advance the modelling. [ABSTRACT FROM AUTHOR]

Since the publication of the latest World Health Organization ( WHO) classification in 2008, there has been a significant effort for clarification of unresolved questions, especially with the help of the rapidly developing field of molecular genetic studies, next-generation sequencing in particular. Numerous entities within the WHO categories of myeloproliferative neoplasms ( MPNs) and myelodysplastic (MDS)/MPNs have been extensively studied, with large published series attempting to characterize and better define their morphologic and molecular genetic features. This emerging genetic landscape maintains a robust correlation with the various disease entities recognized by the WHO classification scheme based on a careful integration of detailed clinical information, bone marrow and peripheral blood morphology, immunohistology, and genomics. This brief review summarizes the current guidelines as they apply to diagnosing both the classical BCR- ABL1 negative MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) and the more common subtypes of MDS/ MPN overlap syndromes. The more important recent molecular updates as well as the upcoming changes to the current WHO classification, expected to be published in late 2016, will also be briefly reviewed. [ABSTRACT FROM AUTHOR]

A novel geometry called the dual-reverse-arrow fractal (DRAF) is introduced, which is the combination of two dual Koch fractals. It is implemented on an equilateral-triangular patch antenna. This structure has smaller dimensions compared to the rectangular structure and has wide applications in arrays to reduce their size. Furthermore, the use of triangular elements in array leads to the decrease of side-lobe levels. Four cases of the triangular patch are compared to show that the presented fractal geometry is effective in the miniaturisation of patch antenna and decreasing its resonance frequency, while the antenna bandwidth and efficiency are kept constant. To increase the antenna efficiency, an air space is placed under the patch. Finally, a portion of the corner of fractal triangle is cut to generate circular polarisation by proper positioning of the feed points. The proposed DRAF antenna achieved 40% reduction in size compared to the similar triangular antenna. The proposed DRAF geometry has potential applications in various radiating systems and microwave devices. [ABSTRACT FROM AUTHOR]

Spinal neurofibromatosis ( SNF) is a related form of neurofibromatosis 1 ( NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/ NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non- SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots ( MNFSR): 4 mixed SNF/ MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio ( OR) = 6.16; confidence interval ( CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271). [ABSTRACT FROM AUTHOR]

Method of least squares is employed for pattern synthesis of non-uniform conical arrays using Euler rotation of coordinate axes. Design specifications involve beam-width of main-lobe, side-lobe and cross-polarisation levels. This method is effective for conformal arrays, because pattern multiplication is not applicable for them. Constructed error function depends on element spacing and current excitations (amplitudes and phases of input currents). Combination of conjugate gradient and genetic algorithms is used for its miniaturisation to determine element spacing and excitations. Recent literature on nonuniform arrays mostly deals with non-uniform excitations with complicated input networks. The non-uniformly spaced arrays will realise any specification obtained by non-uniform excitations. Two examples of non-uniform current excitations are presented. First example leads to reduction of side-lobe level (SLL) from 12 to 20 dB. Second example deals with different upper and lower SLLs. Third example treats non-uniform spacing, which results in the reduction of SLL from 12 to 18 dB. Fourth example synthesises both non-uniform spacing and unequal excitations, which provides the SLL reduction from 12 to 25 dB, besides the reduction of cross-polarisation level from 12 to 25 dB, compared with Qing- Qjang et al. 2011, which decreased SLL by only 8 dB. [ABSTRACT FROM AUTHOR]