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Alessandro Broccoli,1 Clara Bertuzzi,2 Michelangelo Fiorentino,3 Alice Morigi,1 Vittorio Stefoni,1 Claudio Agostinelli,2 Lisa Argnani,1 Michele Cavo,1 Pier Luigi Zinzani11Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy; 2Hematopathology Unit, Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy; 3Pathology Unit, “S.Orsola-Malpighi” Hospital, University of Bologna, Bologna, ItalyAbstract: Hairy cell leukemia (HCL) is an uncommon B-cell chronic lymphoproliferative disorder whose pathogenesis and recurrence are strictly dependent on the presence of the BRAF V600E mutant. A 65-year-old male presented a monomorphic epitheliotropic intestinal T-cell lymphoma (formerly enteropathy-associated T-cell lymphoma, type II) with HCL not responding to first-line induction with cladribine. The intestinal lymphoma bears the BRAF V600E mutant, which is the molecular hallmark of HCL, being implicated in its pathogenesis. The case is of interest, as it provides the first description of a BRAF V600E-positive intestinal T-cell lymphoma, along with immunohistochemical and molecular demonstration, occurring in concomitance with HCL. A novel digital PCR-base method for HCL disease assessment is also suggested.Keywords: hairy-cell leukemia, BRAF V600E mutant, monomorphic epitheliotropic intestinal T-cell lymphoma, cladribine

A Mach–Zehnder interferometer is a basic building block for linear transformations that has been widely applied in optical neural networks. However, its sinusoidal transfer function leads to the inevitable dynamic phase quantization error, which is hard to eliminate through pre-calibration. Here, a strongly overcoupled ring is introduced to compensate for the phase change without adding perceptible loss. Two full-scale linearized Mach–Zehnder interferometers are proposed and experimentally validated to improve the bit precision from 4-bit to 6- and 7-bit, providing ∼3.5× to 6.1 × lower phase quantization errors while maintaining the same scalability. The corresponding optical neural networks demonstrate higher training accuracy. [ABSTRACT FROM AUTHOR]

Annalisa Altimari,1,* Dario de Biase,2,* Giovanna De Maglio,3 Elisa Gruppioni,1 Elisa Capizzi,1 Alessio Degiovanni,1 Antonia D'Errico,1 Annalisa Pession,2 Stefano Pizzolitto,3 Michelangelo Fiorentino,1,# Giovanni Tallini2,#1Laboratory of Molecular Oncologic and Transplantation Pathology, S. Orsola-Malpighi Hospital, Bologna, 2Laboratory of Molecular Pathology, Anatomic Pathology, Bellaria Hospital, Bologna, 3Department of Pathology, S. Maria della Misericordia Hospital, Udine, Italy*These authors contributed equally to this work #These authors share senior authorshipAbstract: Detection of KRAS mutations in archival pathology samples is critical for therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal cancer. We compared the sensitivity, specificity, and accuracy of Sanger sequencing, ARMS-Scorpion (TheraScreen®) real-time polymerase chain reaction (PCR), pyrosequencing, chip array hybridization, and 454 next-generation sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%, and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen real-time PCR, pyrosequencing, and chip array hybridization, respectively. The main limitation of Sanger sequencing was its low analytical sensitivity, whereas TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed higher sensitivity but suffered from the limitations of predesigned assays. Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85 for the other techniques. Tumor cell enrichment correlated significantly with the abundance of KRAS-mutated deoxyribonucleic acid (DNA), evaluated as ΔCt for TheraScreen real-time PCR (P = 0.03), percentage of mutation for pyrosequencing (P = 0.001), ratio for chip array hybridization (P = 0.003), and percentage of mutation for 454 next-generation sequencing (P = 0.004). Also, 454 next-generation sequencing showed the best cross correlation for quantification of mutation abundance compared with all the other methods (P < 0.001). Our comparison showed the superiority of next-generation sequencing over the other techniques in terms of sensitivity and specificity. Next-generation sequencing will replace Sanger sequencing as the reference technique for diagnostic detection of KRAS mutation in archival tumor tissues.Keywords: colorectal cancer, targeted therapy, KRAS mutations, next-generation sequencing, real-time polymerase chain reaction, pyrosequencing

Large-scale computer installations are severely limited by network-bandwidth constraints and energy costs that arise from architectural designs originally based on copper interconnects. Wavelength-division multiplexed (WDM) photonic links can increase the network bandwidth but are sensitive to environmental perturbations and manufacturing imperfections that can affect the precise emission wavelength and output power of laser transmitters. Here, we demonstrate a new design of a three-terminal hybrid III-V-on-silicon laser that integrates a metal-oxide-semiconductor (MOS) capacitor into the laser cavity. The MOS capacitor makes it possible to introduce the plasma-dispersion effect and thus change the laser modal refractive index and free-carrier absorption (FCA) loss to tune the laser wavelength and output power, respectively. The approach enables a highly energy efficient method to tune the output power and wavelength of microring lasers, with future prospects for high-speed, chirp-free direct laser modulation. The concept is potentially applicable to other diode laser platforms. [ABSTRACT FROM AUTHOR]

To investigate the predictive value of Acute Physiology, Age and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology (SAPS) II and Sequential Organ Failure Assessment (SOFA) scores for patient selection and timing to Extracorporeal Life Support (ECLS) as treatment of refractory cardiogenic shock. Retrospective analysis of a prospectively-maintained operative dataset. Our study population included 185 patients receiving ECLS at our department between 2006 and 2018. Patient median age was 50.6 years; 62% were male. The most frequent reason for ECLS need, in our subset of patients, was post-cardiotomy syndrome (52.4%) followed by acute decompensation of chronic heart failure (17.5%), isolated right ventricular dysfunction (16.2%), acute myocardial infarction (10.2%) and myocarditis (3.7%). Median duration of ECLS was 8.9 days. Forty-one patients (22.2%) received heart transplantation. In-hospital mortality was 34.6% on ECLS running and 25.9% after ECLS removal. Multivariate regression analysis showed patient age, ECLS duration and bridge to transplantation (BTT) category as indipendent predictors of death (p <0.001). After adjustment for SAPS II and SOFA scores, age obtained an Hazard Ratio (HR) of 1.22, ECLS duration 2.89 and BTT intention 1.52 while in the adjustment for SAPS II and APACHE II of 1.01, 1.99 and 1.47, respectively. This study confirms the poor prognosis of critically ill patients receiving ECLS support. The APACHE II and SOFA scores, mainly, proved to be a reproducible evaluation tool with high prognostic abilities. In our population, age >65 years, ECLS duration >10 days and BTT ECLS intention appear to impact negatively. [ABSTRACT FROM AUTHOR]

In 2004 the ADONHERS Protocol was created to increase the number of suitable heart donations. It's applied in extended criteria donors and in cases of impossibility to perform coronary angiography. We present the detailed protocol and clinical results of patients transplanted with. The ADHONERS Protocol (AP) included: administration of defined doses of dipyridamole or dobutamine; basal and after test evaluation of regional motion, on a scale from 1 (normal) to 4 (dyskinetic) in each of the 17 segments; sharing of echo images with a second opinion. We included 275 cardiac transplantations performed from 2004 to 2014. Of them, 23 (8.4%) were performed applying the AP. Recently, we used the echo stress in three procurements where coronary angiogram couldn't be performed, with excellent results and no coronary stenosis on the post-transplant angio. Those cases are not included in this cohort. In AP group, recipients were older (55,8 years vs 51,5 p = 0,079) as well as donors (54,5 years vs 37,8 in the NAP (non ADONHERS Protocol) group, p=0.001), while mean ischemic time was shorter (181,9 min vs 197,2 min, p=0.008) and the use of Adrenaline or Dobutamine in donors was inferior (22.7% in AP vs 56.2% in NAP p=0.033). Early and late outcomes were analogous in the two groups. Severe EGF occurred in 8,7% patients AP vs 8,3% in NAP (p=0,95). In hospital mortality of NAP group was 7,9% vs 8.7% (p=0,749). No coronary disease (CAD) was found in the early postop but in the long term CAD occurred in two cases of the AP group (9.5%) vs 12 cases in NAP (5.2%) (p=0.33). Mean follow up time was 74,7 months in AP vs 110,1 (p=0,001) and follow up survival at 1 and 5 years in the AP group was 91.3% and 73% vs 89.7% and 80.9% (p=0.019), but population in the AP group was older. In hospital mortality risk factors were: recipients' age [OR 1.07 (1.01;1.13), p=0.016] and donors' age [OR 1.05 (1.01 ; 1.09), p=0.009], while in the follow-up were recipients' age [1.04 (1.02;1.06), p=0.001], vasculopathy [OR 4.75 (1.28;17.68), p=0.018], donors' age [OR 1.03 (1.01;1.05), p=0.006], donor female gender [OR 2.51 (1.51;4.17) , p=0.00] and gender mismatch [OR 2.28 (1.32 ; 3.96) , p=0.003] Applying the ADONHERS protocol nearly 10% of otherwise discarded hearts can be successfully used for transplantation to unmask inducible ischemia and estimate contractile reserve. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine (i) the variation in the bacterial population, (ii) the changes in the number of aerobic bacteria, and (iii) in vitro bacterial susceptibility to different antibiotics after the use of two different intravaginal devices (silicone devices or polyurethane sponges) for 6 or 11 days in goats. During the breeding season, 25 multiparous Saanen goats were randomly allocated to four treatments. Group IS-6 (n = 6) and Group IS-11 (n = 6) goats received a polyurethane intravaginal sponge (60 mg medroxyprogesterone acetate with oxytetracycline in powder) during 6 or 11 days, respectively. Goats from groups SD-6 (n = 7) and SD-11 (n = 6) received an intravaginal silicone device (0.3 g progesterone) during 6 or 11 days, respectively. Before the introduction of the devices, at device withdrawal, and the day of oestrus we performed standard bacteriological procedures on vaginal mucus samples. The predominant bacterial flora at device insertion was gram-positive (77%), and the most frequent strain was Bacilllus sp. The samples obtained on Day 6 [SD-6: 9/12 (75.0%); IS-6: 5/9 (55.5%)] and Day 11 [SD-11: 3/4 (75.0%); IS-11: 5/5 (100%)] were predominantly gramnegative, and the most frequently isolated bacteria was Arcanobacterium pyogenes. The total number of aerobic bacteria forming colony units (CFU/mL) was greater in goats treated with inert silicon device that those treated with intravaginal sponges (P = 0.028). On device removal (Days 6 and 11), we observed more CFU/mL than on device insertion. We observed no difference in CFU/mL on day of oestrus with respect to the day of device insertion (Day 0: 41.1 ± 19.3; Day 6: 187.1 ± 51.3; Day 11: 169.1 ± 27.8; day of oestrus: 20.1 ± 25.8 CFU 103/mL; P < 0.05). The in vitro studies demonstrated that most samples were resistant to oxytetracycline. We concluded that the use of intravaginal devices, regardless of their composition, provoked an increase in the normal vaginal bacterial flora, but values returned to pre-insertion numbers by the day of oestrus. According to in vitro results, amoxicillin, ampicillin and streptomycin were the most effective antibiotics to prevent vaginal bacterial growth. [ABSTRACT FROM AUTHOR]