XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53

Additional file 1. Table S1: Clinicopathologic and molecular characteristics of DLBCL patients with high or low XPO1 expression. Table S2: Significantly differentially expressed genes between XPO1high and XPO1low DLBCL patients with concurrent TP53 mutation and high MYC expression. Figure S1: Biomarker study for XPO1 and selinexor. (A–B) XPO1high expression showed significant adverse prognostic impact in the ABC subtype but not the GCB subtype of DLBCL. (C) XPO1high expression showed a trend of unfavorable prognostic effect on PFS in MYC-rearranged (MYC-R+) DLBCL. (D) XPO1high expression was associated with significantly poorer survival in DLBCL patients with wild type (Wt) TP53. (E) ABC-DLBCL and GCB-DLBCL cells showed similar sensitivity to the cytotoxicity of selinexor. (F) TP53 mutation (Mut-TP53) significantly reduced the anti-lymphoma efficacy of selinexor in HGBCL-DH cells. IC50 values were calculated by GraphPad Prism 8 based on the cell viability data after 72-hour treatment

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Male breast cancer in BRCA1 and BRCA2 mutation carriers : pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Peer reviewe

Water vapour adsorption on modified active carbons

Przeprowadzono modyfikacje węgla aktywnego w celu poprawy jego hydrofilowych właściwości. Handlowy węgiel aktywny typu N poddano utlenianiu za pomocą stężonego kwasu azotowego, nasycaniu roztworem mocznika i wygrzewaniu w wysokiej temperaturze oraz wygrzewaniu w wysokiej temperaturze w atmosferze amoniaku i argonu. Właściwości adsorpcyjne modyfikowanych węgli aktywnych charakteryzowano na podstawie izoterm adsorpcji pary wodnej zmierzonych w temperaturze 25°C. Te izotermy opisano za pomocą równania Dubinina-Astachova z trzema parametrami: a₀ - graniczną wartością adsorpcji, E₀ - charakterystyczną energia adsorpcji i n - parametrem charakteryzującym funkcję rozkładu potencjału adsorpcyjnego. Stwierdzono, że zaproponowane modyfikacje znacząco poprawiają właściwości hydrofilowe badanego węgla aktywnego, co odzwierciedla się w zwiększeniu ilości adsorbowanej wody. Właściwości adsorpcyjne węgla aktywnego N modyfikowanego za pomocą stężonego kwasu azotowego i wygrzewanego w atmosferze amoniaku w temperaturze 800°C są lepsze o blisko 80% w stosunku do wyjściowego węgla. Potwierdzono również przydatność równania Dubinina-Astachova do opisu doświadczalnych izoterm adsorpcji pary wodnej na węglach aktywnych o zróżnicowanych właściwościach powierzchni i struktury porowatej.Modification of active carbon was performed in order to improve its hydrophilic properties. Commercial active carbon N was subjected to oxidation with concentrated nitric acid, immersed with urea solution and heated at high temperature, or heated at high temperature in ammonia and argon. Adsorption properties of modified active carbons were characterized on the basis of water vapour adsorption isotherms measured at 25°C. These isotherms were analyzed by means of Dubinin-Astakhov equation having three parameters: a₀ - maximum adsorption, E₀ - characteristic adsorption energy, and n - parameter characterizing the shape of adsorption potential distribution. It is shown that the modification recipes used improved hydrophilic properties of the active carbon studied, which is reflected by enhanced adsorption of water vapour. Adsorption properties of carbon N modified with concentrated nitric acid and heated in ammonia at a temperature of 800°C are better of about 80% in relation to unmodified carbon. Also, it was shown that Dubinin-Astakhov equation represents well adsorption isotherms of water vapour on active carbons of differentiated surface and structural properties

Application of Carbon Tetrachloride for Characterizing the Adsorption Properties of Ordered Mesoporous MCM-48 Silica.

W pracy omówiono możliwości wykorzystania tetrachlorku węgla do charakterystyki struktury porowatej 3D regularnych uporządkowanych materiałów krzemionkowych z rodziny MCM-48. Próbki materiałów MCM-48 zsyntezowano w temperaturze pokojowej, stosując jako wzorce surfaktanty kationowe - bromki alkilotrimetyloamoniowe o różnej długości łańcucha alkilowego zawierającego od 10 do 18 atomów węgla oraz tetraetoksysilan (TEOS) jako źródło krzemionki. Rzadko stosowana synteza MCM-48 w temperaturze pokojowej pozwoliła uzyskać materiały o dużej powierzchni właściwej i dużej objętości mezoporów. Na podstawie doświadczalnych izoterm adsorpcji tetrachlorku węgla zmierzonych w temperaturze 298 K wyznaczono całkowitą powierzchnię właściwą, całkowitą objętość porów, objętość pierwotnych mezoporów, funkcje rozkładu objętości porów oraz wymiar porów odpowiadający maksimum tych funkcji. Porównując parametry struktury porowatej materiałów MCM-48, uzyskane na podstawie adsorpcji CCl4, z parametrami uzyskanymi na podstawie adsorpcji N2, stwierdzono, że ten pierwszy adsorbat może być również z powodzeniem wykorzystywany do charakterystyki właściwości adsorpcyjnych uporządkowanych krzemionek i analogicznych materiałów. Badania wykazały, że materiały MCM-48 mogą być stosowane do pochłaniania substancji organicznych w procesie oczyszczania powietrza.This work is focused on the use of carbon tetrachloride for the characterization of ordered mesoporous MCM-48 silica (3D regular structure). A series of MCM-48 samples was synthesized at room temperature using cationic surfactants, alkyltrimethylammonium bromides with alkyl chains having from 10 to 18 carbon atoms, and tetraethylorthosilicate (TEOS) as silica source. It is noteworthy that the seldom used synthesis of MCM-48 at room temperature afforded materials with high surface area and large volume of mesopores. Experimental adsorption isotherms for carbon tetrachloride measured at 298 K were used to evaluate the total specific surface area, total pore volume, volume of primary mesopores, pore size distribution (PSD) and the pore width corresponding to the maximum of PSD. A comparison of adsorption parameters evaluated from adsorption data for CCl4 on the MCM-48 samples with those obtained from nitrogen data shows that CCl4 can be also used for the characterization of ordered mesoporous silica and related materials. This study shows that MCM-48 materials may be useful for the removal of organic vapors such as CCl4 from air

Dynamic resource and task management

Carrying out maritime missions comprises many phases from preparation to execution. In the long term, we would like to have an integrated toolchain that supports the crew at every phase. In this chapter, we study concepts for resource and task management in the execution phase. When the tasks to be executed have been identified, the question arises who should be assigned to them. This is both a scheduling and an assignment problem. We narrow down what kind of problem we have at hand to get an understanding what a first step towards an integrated command and control system could look like. This also enables us to classify our problem with the existing literature on planning and scheduling. We develop a domain model for tasks and resources, their connection via capabilities, together with assessment functions to compare assignments. We study what kind of information would be needed to give useful scheduling advice

Vasoactives Intestinales Polypeptid (VIP): Sekretionsmuster nach intraduodenaler Fettapplikation beim Stoffwechselgesunden und Diabetiker

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman