Algorithmic Superactivation of Asymptotic Quantum Capacity of Zero-Capacity Quantum Channels

The superactivation of zero-capacity quantum channels makes it possible to use two zero-capacity quantum channels with a positive joint capacity for their output. Currently, we have no theoretical background to describe all possible combinations of superactive zero-capacity channels; hence, there may be many other possible combinations. In practice, to discover such superactive zero-capacity channel-pairs, we must analyze an extremely large set of possible quantum states, channel models, and channel probabilities. There is still no extremely efficient algorithmic tool for this purpose. This paper shows an efficient algorithmical method of finding such combinations. Our method can be a very valuable tool for improving the results of fault-tolerant quantum computation and possible communication techniques over very noisy quantum channels.Comment: 35 pages, 17 figures, Journal-ref: Information Sciences (Elsevier, 2012), presented in part at Quantum Information Processing 2012 (QIP2012), v2: minor changes, v3: published version; Information Sciences, Elsevier, ISSN: 0020-0255; 201

Investigation of the mechanical and chemical characteristics of nanotubular and nano-pitted anodic films on grade 2 titanium dental implant materials

Abstract Objective The objective of this study was to investigate the reproducibility, mechanical integrity, surface characteristics and corrosion behavior of nanotubular (NT) titanium oxide arrays in comparison with a novel nano-pitted (NP) anodic film. Methods Surface treatment processes were developed to grow homogenous NT and NP anodic films on the surface of grade 2 titanium discs and dental implants. The effect of process parameters on the surface characteristics and reproducibility of the anodic films was investigated and optimized. The mechanical integrity of the NT and NP anodic films were investigated by scanning electron microscopy, surface roughness measurement, scratch resistance and screwing tests, while the chemical and physicochemical properties were investigated in corrosion tests, contact angle measurement and X-ray photoelectron spectroscopy (XPS). Results and discussion The growth of NT anodic films was highly affected by process parameters, especially by temperature, and they were apt to corrosion and exfoliation. In contrast, the anodic growth of NP film showed high reproducibility even on the surface of 3-dimensional screw dental implants and they did not show signs of corrosion and exfoliation. The underlying reason of the difference in the tendency for exfoliation of the NT and NP anodic films is unclear; however the XPS analysis revealed fluorine dopants in a magnitude larger concentration on NT anodic film than on NP surface, which was identified as a possible causative. Concerning other surface characteristics that are supposed to affect the biological behavior of titanium implants, surface roughness values were found to be similar, whereas considerable differences were revealed in the wettability of the NT and NP anodic films. Conclusion Our findings suggest that the applicability of NT anodic films on the surface of titanium bone implants may be limited because of mechanical considerations. In contrast, it is worth to consider the applicability of nano-pitted anodic films over nanotubular arrays for the enhancement of the biological properties of titanium implants

Relabáló/refrakter Hodgkin-lymphoma brentuximab vedotin kezelése. Hazai tapasztalatok

Introduction: The treatment of relapsed or refractory Hodgkin lymphoma is still a major therapeutic challenge. The use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, represents a promising approach for these patients, however clinical outcomes have not yet been evaluated in Hungary. Aim: Our aim was to assess the efficacy, safety and outcome of brentuximab vedotin treatment in Hungarian Hodgkin lymphoma patients. Method: In this retrospective case note review we enrolled patients at 6 clinical sites countrywide who were diagnosed with Hodgkin lymphoma and received brentuximab vedotin between 1 January 2013 and 31 December 2016. Results: A total of 86 patients were treated with brentuximab vedotin during the examined period. Before therapy initiation 66% of our patients had advanced-stage disease. Overall response rate to brentuximab vedotin, administered before autologous hematopoietic stem cell transplantation (n = 54) was 66.6%, complete remission rate was 42.6%. Thirty patients received brentuximab vedotin after AHSCT, 46.67% responded to treatment, 30% achieved complete remission. Thirty-six patients received the drug as a single-agent therapy, 50 patients were given brentuximab vedotin in combination, 39 of them with bendamustin. Toxicity was observed only in 13.95% of our patients, most common symptom was skin rash. Based on our analysis the estimated 5-year overall survival rate was 78.7%, the estimated progression free survival rate was 23.59 months (95% CI: 19.50-27.68). Conclusion: Brentuximab vedotin carries a substantial improvement in the treatment of relapsed or refractory Hodgkin lymphoma. Our results underline prior observations published in the literature. The use of brentuximab vedotin in combination can be beneficial, however further investigation is needed on the subject

Relabáló/refrakter Hodgkin-lymphoma brentuximab vedotin kezelése. Hazai tapasztalatok | Brentuximab vedotin treatment in patients with relapsed or refractory Hodgkin lymphoma. A Hungarian retrospective study

Absztrakt: Bevezetés: A relabáló és refrakter Hodgkin-lymphoma kezelése továbbra is nagy kihívást jelent. Hatalmas előrelépést jelentett a brentuximab vedotin alkalmazása, amellyel jelenleg már jelentős hazai tapasztalatok is vannak. Célkitűzés: A brentuximab vedotinnal kezelt magyar Hodgkin-lymphomás betegek adatainak, a kezelés hatékonyságának elemzése. Módszer: Hat hazai hematológiai osztályon 2013. január 1. és 2016. december 31. között brentuximab vedotinnal kezelt Hodgkin-lymphomás betegek adatainak retrospektív elemzése. Eredmények: Összesen 86 beteg részesült brentuximab vedotin kezelésben. A kezelés előtt a betegek egyharmada korai, kétharmada előrehaladott stádiumban volt. Autológ őssejt-transzplantáció előtt alkalmazva 54 betegnél a teljes válaszarány 66,6%, ebből komplett remissziót a betegek 42,6%-a ért el. Autológ őssejt-transzplantációt követően 30 beteg kapta, a teljes válaszarány 46,67%, a komplett remisszió 30% volt. Harminchat beteg csak monoterápiában kapta a készítményt, míg 50 beteg kombinációban, ebből 39 esetben bendamustinnal kombináltan. A betegek mindössze 13,95%-ánál észleltünk mellékhatást, leggyakrabban bőrkiütést. A betegek várható ötéves teljes túlélése 78,7%, az átlagos progressziómentes túlélési idő 23,59 hónap (95% CI: 19,50–27,68). Következtetés: A relabáló vagy refrakter Hodgkin-lymphomás betegek kezelésében jelentős előrelépést jelent a brentuximab vedotin kezelés alkalmazása, eredményeink a nemzetközi adatokhoz hasonlóak. A kombinációban történő korai alkalmazása előrelépést jelenthet, ennek további vizsgálata szükséges. Orv Hetil. 2017; 158(41): 1630–1634. | Abstract: Introduction: The treatment of relapsed or refractory Hodgkin lymphoma is still a major therapeutic challenge. The use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, represents a promising approach for these patients, however clinical outcomes have not yet been evaluated in Hungary. Aim: Our aim was to assess the efficacy, safety and outcome of brentuximab vedotin treatment in Hungarian Hodgkin lymphoma patients. Method: In this retrospective case note review we enrolled patients at 6 clinical sites countrywide who were diagnosed with Hodgkin lymphoma and received brentuximab vedotin between 1 January 2013 and 31 December 2016. Results: A total of 86 patients were treated with brentuximab vedotin during the examined period. Before therapy initiation 66% of our patients had advanced-stage disease. Overall response rate to brentuximab vedotin, administered before autologous hematopoietic stem cell transplantation (n = 54) was 66.6%, complete remission rate was 42.6%. Thirty patients received brentuximab vedotin after AHSCT, 46.67% responded to treatment, 30% achieved complete remission. Thirty-six patients received the drug as a single-agent therapy, 50 patients were given brentuximab vedotin in combination, 39 of them with bendamustin. Toxicity was observed only in 13.95% of our patients, most common symptom was skin rash. Based on our analysis the estimated 5-year overall survival rate was 78.7%, the estimated progression free survival rate was 23.59 months (95% CI: 19.50–27.68). Conclusion: Brentuximab vedotin carries a substantial improvement in the treatment of relapsed or refractory Hodgkin lymphoma. Our results underline prior observations published in the literature. The use of brentuximab vedotin in combination can be beneficial, however further investigation is needed on the subject. Orv Hetil. 2017; 158(41): 1630–1634

Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

We generated ex vivo drug-response and multiomics profi ling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identifi cation of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profi ling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine. SIGNIFICANCE: Oncogenomics data can guide clinical treatment decisions, but often such data are neither actionable nor predictive. Functional ex vivo drug testing contributes signifi cant additional, clinically actionable therapeutic insights for individual patients with AML. Such data can be generated in four days, enabling rapid translation through FPMTB.Peer reviewe

Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

We generated ex vivo drug-response and multiomics profi ling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identifi cation of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profi ling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine. SIGNIFICANCE: Oncogenomics data can guide clinical treatment decisions, but often such data are neither actionable nor predictive. Functional ex vivo drug testing contributes signifi cant additional, clinically actionable therapeutic insights for individual patients with AML. Such data can be generated in four days, enabling rapid translation through FPMTB.Peer reviewe

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis

FcRn Overexpression in Transgenic Mice Results in Augmented APC Activity and Robust Immune Response with Increased Diversity of Induced Antibodies

Our previous studies have shown that overexpression of bovine FcRn (bFcRn) in transgenic (Tg) mice leads to an increase in the humoral immune response, characterized by larger numbers of Ag-specific B cells and other immune cells in secondary lymphoid organs and higher levels of circulating Ag-specific antibodies (Abs). To gain additional insights into the mechanisms underlying this increase in humoral immune response, we further characterized the bFcRn Tg mice. Our Western blot analysis showed strong expression of the bFcRn transgene in peritoneal macrophages and bone marrow derived dendritic cells; and a quantitative PCR analysis demonstrated that the expression ratios of the bFcRn to mFcRn were 2.6- and 10-fold in these cells, respectively. We also found that overexpression of bFcRn enhances the phagocytosis of Ag-IgG immune complexes (ICs) by both macrophages and dendritic cells and significantly improves Ag presentation by dendritic cells. Finally, we determined that immunized bFcRn mice produce a much greater diversity of Ag-specific IgM, whereas only the levels, but not the diversity, of IgG is increased by overexpression of bFcRn. We suggest that the increase in diversity of IgG in Tg mice is prevented by a selective bias towards immunodominant epitopes of ovalbumin, which was used in this study as a model antigen. These results are also in line with our previous reports describing a substantial increase in the levels of Ag-specific IgG in FcRn Tg mice immunized with Ags that are weakly immunogenic and, therefore, not affected by immunodominance

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts