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Production of quantum states exhibiting a high degree of entanglement out of noisy conditions is one of the main goals of quantum information science. Here, we provide a conditional yet efficient entanglement distillation method which functions within the framework of spatially localized operations and classical communication. This method exploits indistinguishability effects due to the spatial overlap between two identical qubits in distinct sites and encompasses particle statistics imprint. We derive the general conditions for the maximum entanglement distillation out of mixed states. As applications, we give a thorough description of distilled entanglement and associated success probability starting from typical noisy states, such as thermal Gibbs states and Werner states. The influence of local temperatures and of noise parameter is discussed, respectively, in these two cases. The proposed scheme paves the way towards quantum repeaters in composite networks made of controllable identical quantum particles., 9 pages, 6 figures

Glaciers and ice caps in the Tien Shan mountains play a crucial role in terms of water supply for irrigation, industry and drinking. The retreat of these ice masses can consequently have a major impact on downstream densely populated dry lowland areas. Therefore, it is crucial to understand how ice masses in the Tien Shan are reacting to climate change and how they will evolve in the future. In this study, we model the future evolution of all glaciers and ice caps in the Tien Shan mountains under CMIP6 SSP climate scenarios using the large-scale GloGEMflow model. The model is calibrated to match glacier-specific geodetic mass balances while accounting for debris cover under recent climatic conditions (downscaled climate reanalysis, ERA5). In our modelling framework, we rely on a total of six independent ice thickness datasets, of which the effect on the modelled future glacier evolution is analysed in detail. Our results reveal an exceptionally pronounced retreat of most of the ice masses under all climate scenarios (vs. other regions), which can be related to the specific climate regime. Since most of the precipitation on Tien Shan glaciers occurs in spring and early summer, temperature increases not only increase melt (as is the case in most regions around the world), but additionally strongly influence the precipitation type (solid vs. liquid). In all scenarios, the total runoff for the major river catchments in the Tien Shan is projected to drastically reduce by the end of the 21st century. Further, peak water is modelled to be reached before the middle of the century and the annual runoff peak is anticipated to shift from early summer towards late spring.

Background: Ceftazidime/avibactam (CAZ-AVI) resistance amongst Enterobacterales is worryingly increasing worldwide. Objectives: The aim of this study was to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae (KP) isolates in our University Hospital, with the ultimate goal of evaluating possible risk factors related to the acquisition of resistance. Methods: This is a retrospective observational study, including unique Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI (CAZ-AVI-R) and producing only KPC, collected from July 2019 to August 2021 at Policlinico Tor Vergata, Rome, Italy. The pathogen’s list was obtained from the microbiology laboratory; clinical charts of the corresponding patients were reviewed to collect demographic and clinical data. Subjects treated as outpatients or hospitalized for

Expression microarray studies available in the Oncomine database that met our eligibility criteria.

Table S1A: Signature of 998 differentially expressed genes between various resistant IGR-CaP1 cells and parental IGR-CaP1 Table S1B: Gene Ontology information on the 998 gene signature Table S2A: List of the 34 upregulated hits from the image-based high-content screen Table S2B: Gene Ontology information about the 34 hits issued from the image-based screen Table S3: Clinical data of patients recruited for tissue microarray (TMA) Table S4A: Specific partners of FKBP7 in RPE-1 cells Table S4B: Specific partners of FKBP7 in IGR-CaP1-Dtx-R cells Table S5A: SILAC on RPE-1 cells. Table S5B: SILAC on IGR-CaP1-Dtx-R cells.

Interaction of FKBP7 with eIF4G

Bioinformatic analysis of human prostate adenocarcinoma microarray datasets. Oncomine was used to browse gene expression microarrays data. Box plots depict prostate statistics derived from Grasso et al. LGALS1, CD34, FLT1, FLT4, VEGFA, VEGFC, VCAM1, CD28, CD80 and CD86 were assessed. Each box plot shows the expression levels for each gene in 1) normal prostate gland and 2) prostate adenocarcinoma. * indicates P

Supplementary material and methods

Purpose: Conditioning strategies constitute a relatively unexplored and exciting opportunity to shape tumor fate by targeting the tumor microenvironment. In this study, we assessed how hemin, a pharmacologic inducer of heme oxygenase-1 (HO-1), has an impact on prostate cancer development in an in vivo conditioning model.Experimental Design: The stroma of C57BL/6 mice was conditioned by subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge. Complementary in vitro and in vivo assays were performed to evaluate hemin effect on both angiogenesis and the immune response. To gain clinical insight, we used prostate cancer patient-derived samples in our studies to assess the expression of HO-1 and other relevant genes.Results: Conditioning resulted in increased tumor latency and decreased initial growth rate. Histologic analysis of tumors grown in conditioned mice revealed impaired vascularization. Hemin-treated human umbilical vein endothelial cells (HUVEC) exhibited decreased tubulogenesis in vitro only in the presence of TRAMP-C1–conditioned media. Subcutaneous hemin conditioning hindered tumor-associated neovascularization in an in vivo Matrigel plug assay. In addition, hemin boosted CD8+ T-cell proliferation and degranulation in vitro and antigen-specific cytotoxicity in vivo. A significant systemic increase in CD8+ T-cell frequency was observed in preconditioned tumor-bearing mice. Tumors from hemin-conditioned mice showed reduced expression of galectin-1 (Gal-1), key modulator of tumor angiogenesis and immunity, evidencing persistent remodeling of the microenvironment. We also found a subset of prostate cancer patient-derived xenografts and prostate cancer patient samples with mild HO-1 and low Gal-1 expression levels.Conclusions: These results highlight a novel function of a human-used drug as a means of boosting the antitumor response. Clin Cancer Res; 23(17); 5135–48. ©2017 AACR.

Supplementary figure legends

Purpose:Targeted therapies that use the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes for men. Molecular chaperones play a key role in the regulation of protein homeostasis and are potential targets for overcoming chemoresistance.Experimental Design: We established 4 chemoresistant prostate cancer cell lines and used image-based high-content siRNA functional screening, based on gene-expression signature, to explore mechanisms of chemoresistance and identify new potential targets with potential roles in taxane resistance. The functional role of a new target was assessed by in vitro and in vivo silencing, and mass spectrometry analysis was used to identify its downstream effectors.Results:We identified FKBP7, a prolyl-peptidyl isomerase overexpressed in docetaxel-resistant and in cabazitaxel-resistant prostate cancer cells. This is the first study to characterize the function of human FKBP7 and explore its role in cancer. We discovered that FKBP7 was upregulated in human prostate cancers and its expression correlated with the recurrence observed in patients receiving docetaxel. FKBP7 silencing showed that FKBP7 is required to maintain the growth of chemoresistant cell lines and chemoresistant tumors in mice. Mass spectrometry analysis revealed that FKBP7 interacts with eIF4G, a component of the eIF4F translation initiation complex, to mediate the survival of chemoresistant cells. Using small-molecule inhibitors of eIF4A, the RNA helicase component of eIF4F, we were able to kill docetaxel- and cabazitaxel-resistant cells.Conclusions:Targeting FKBP7 or the eIF4G-containing eIF4F translation initiation complex could be novel therapeutic strategies to eradicate taxane-resistant prostate cancer cells.

Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the “galectin signature” of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated “galectin-specific signature” that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease. Cancer Res; 73(1); 86–96. ©2012 AACR.

PDF file - 88K, Table S1. Primers used to delineate the 'galectin signature' of prostate cancer cells Table S2. Primers used to determine angiogenesis-related genes

PDF file - 123K, Figure S1. Gal-1 mRNA expression and PSA mRNA expression in hormone-responsive (HR) and castration-resistant (CR) LNCaP cells Figure S2: Immunoreactivity of anti-galectin antibodies

Il contributo muove dallo studio delle possibili connessioni epistemiche tra l’Educazione personalizzata e la Didattica inclusiva e, al contempo, intende pagare un tributo al Prof. G. Zanniello (1997) cui va il merito di aver fatto conoscere in Italia il sistema dell’educazione personalizzata di Victor García Hoz prima che l’espressione “personalizzazione educativa” fosse inserita per la prima volta in una legge scolastica italiana (n. 53/2003).

The present work focuses on the construct of digital citizenship from an educational and inclusive point of view. Considering the general European interest in implementing citizens’ digital skills and with particular care for the contemporary situ-ation of overall emergency, due to the Covid 19 pandemic case, the idea is that of con-sidering a possible conceptual link between digital skills and the Capability Approach. In the light of an ‘Education for all’, the aware development of teachers and, particu-larly support teachers’ digital skills, may be a crucial key to enact inclusive processes able to guarantee any pupil and student the chance to become a capable and valu-able citizen, despite his/her frailties and social failures. This paper is part of a wider research project entitled “Best practices and tools of analysis in schools and commu-nity contexts: learning, teaching & inclusion”, started in March 2019 and funded by the Department of Psychological, Pedagogical Sciences, Physical Exercise and Training, of the University of Palermo, and of which just a segment related to the analysis of sup-port teachers’ digital competence is reported here

Les récits par et sur le numérique : introduction Depuis une vingtaine à une trentaine d’années, les évolutions numériques propres à la place grandissante dans les activités du quotidien de l’informatique d’une manière générale, – et plus particulièrement d’Internet, des jeux vidéo et des réseaux sociaux – les récits et discours que nous contribuons à concevoir sont perceptibles sous des angles d’approches de plus en plus variés. Alors même que ces formes sont apparues et se développent, les ...

Galectins play relevant roles in tumor development, progression and metastasis. Accordingly, galectins are certainly enticing targets for medical intervention in cancer. To date, however, clinical trials based on galectin inhibitors reported inconclusive results. This review summarizes the galectin inhibitors currently being evaluated and discusses some of the biological challenges that need to be addressed to improve these strategies for the benefit of cancer patients.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35–14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC.

Background Several studies reported an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) assay results in patients with severe Coronavirus Disease (COVID)-19. Methods Aim of the study was to longitudinally evaluate QFT-P responses in patients who survived COVID-19, with a previous indeterminate result. Results We observed 223 patients with an indeterminate QFT-P assay among 949 patients hospitalized because of COVID-19 (23,5%) during 2020 and 2021. 36 patients among those with an indeterminate QFT-P assay were enrolled for reassessing the test. In 12 patients peripheral blood lymphocyte subsets were also reassessed. Considering disease severity, 30 were classified as severe and 6 as non-severe. Median age was 57,5 (interquartile range [IQR]: 49,5-63,8), with a prevalence of male sex (M/F: 24/12); median Charlson Comorbidity Index was 2 (IQR: 1-3). The second QFT-P assay was performed after at least 1 month from the first assay (median time 7 months, IQR: 5-12 months). All QFT-P assays gave a determined result: 2 positive (5.5%) and 34 negatives (94,4%). A statistically significant difference was observed after comparing the laboratory parameters at the time of the first and the second QFT-P assay: the absolute counts of total lymphocyte, total CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased (p< 0.001) while neutrophil absolute counts, neutrophil to lymphocyte (N/L) ratio, D-dimer, fibrinogen, ferritin, C-reactive protein (CRP) were significantly reduced (p< 0.0001). Concerning the QFT-P assay, interferon gamma (INF-γ) production in the Mitogen-Nil, TB1-Nil and TB2-Nil conditions were significantly increased (p< 0.0001; p=0.0019; p=0.0205, respectively) (Table 1 and Figure 1). Conclusion Once the acute phase of COVID-19 is resolved, inflammatory markers and peripheral blood leucocyte counts tend to normalize with an effective INF-γ production after specific and nonspecific stimulation. All the 36 QFT-P showed a determinate result. Moreover, we observed 2 positive QFT-P assay, supporting the importance of retesting patients with indeterminate result to identify latent tuberculosis infection and monitor patients for possible reactivation because of the immune-suppression associated with COVID-19. Disclosures All Authors: No reported disclosures.

Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and prolonged immunodeficiency and the incidence of tuberculosis (TB) disease in those patients is 10 to 40 times higher than the general population Methods This retrospective study performed at Tor Vergata University Hospital in Rome (Italy) included all adult patients who underwent a HSCT in the Hematologic Transplant Unit from January 2015 to December 2019. Data on TB screening, performed through interferon-γ release assay (IGRA), were collected; patients were observed for TB reactivation in a follow up period of at least 3 years Results 323 HSCT recipients were enrolled in this study. Patients’ characteristics are summarized in table 1. 63 patients (19.5%) were not screened for TB, of which 6.3% were born overseas. 260 HSCT recipients (80.5%) were screened: 228 patients (87.7%) had a negative IGRA result, 21 (8.1%) tested positive, and 11 (4.2%) had an indeterminate result. 98.5% were screened before the HSCT. Of the 21 patients with a positive pre-HSCT IGRA test, 14 (66.7%) were males and significantly (p< 0.001) older (median age 60 [IQR] 58-65 years) than those with negative or indeterminate results. Almost all patients (95.2%) were Italian. Patients with a positive IGRA showed a higher monocyte count compared to the other groups (p=0.044), while those with indeterminate IGRA showed a tendence to lower lymphocyte absolute counts, compared to the other groups (p=0.060) (Table 2). All the 21 patients with a pre-HSCT positive IGRA test were radiologically and clinically screened for active TB and, once it was ruled out, treated for latent TB (LTBI) with isoniazid (INH) for 6 months. No events of toxicity or treatment interruption were reported. None of the patients was treated with rifampin. None of the 21 patients with pre-HSCT positive IGRA test developed active TB during the follow up period. Table 1.Characteristics of the study population, overall and divided according to IGRA testingTable 2.Characteristics of the IGRA tested patients, overall and divided by IGRA test results Conclusion To our knowledge, this is the first Italian study on the prevalence of LTBI in patients undergoing HSCT. 8.1% of the 260 patients screened with an IGRA tested positive. The great majority (95.2%) of LTBI patients were Italian and significantly older than IGRA-negative patients. All LTBI HSCT patients received INH treatment and no drug toxicity, nor TB reactivation was observed during the follow-up period Disclosures All Authors: No reported disclosures.

Neuropsychiatric symptoms have been reported in patients receiving dolutegravir, a known inhibitor of the renal and neuronal-expressed organic anion transporter 2 (encoded by SLC22A2 gene). The effect of the genetic variant SLC22A2 808C>A on dolutegravir discontinuation was assessed and analyzed by real-time PCR. We enrolled 627 participants: CA/AA carriers showed a higher prevalence of pre-existing psychiatric comorbidities and use of antidepressants. After 27.9 months, 108 participants discontinued dolutegravir, 64 for neuropsychiatric symptoms. Patients with pre-existing psychiatric comorbidities were at higher risk of dolutegravir discontinuation, while patients carrying the SLC22A2 CA/AA genotype were not. Combining the two variables, an opposite effect of SLC22A2 variants according to pre-existing psychiatric disorders was observed. Using multivariate Cox models, the combined variable pre-existing psychiatric comorbidities/SLC22A2 variants and the use of non-tenofovir alafenamide containing antiretroviral regimens were predictors of dolutegravir discontinuation for neuropsychiatric symptoms. Within 30 days, the majority of participants had a complete resolution of symptoms (61.8%), while 32.7% and 5.5% had partial or no change after dolutegravir discontinuation, respectively. Discontinuation of dolutegravir for neuropsychiatric symptoms was not uncommon and more frequent in participants with pre-existing psychiatric disorders. We described an interaction between SLC22A2 genetic variant and psychiatric comorbidities. In 38.2% of patients, a complete neuropsychiatric symptoms resolution was not observed after dolutegravir discontinuation suggesting the involvement of additional factors.

Background The extension of HIV reservoir in the rectal gut associated lymphoid tissue (GALT) and the ART influence on this compartment are still poorly studied. We aimed to evaluate the extent of HIV-DNA in GALT and peripheral blood of virologically suppressed patients (VS) Methods 40 HIV-1+ VS pts were enrolled. Blood and GALT HIV-DNA levels and residual plasma viremia (RV) were quantified by droplet digital-PCR. Rectal biopsies were collected during high resolution anoscopy. Lymphocyte (L) phenotype and antiretroviral drug concentrations were analysed in tissue and peripheral blood Results Pts median age (IQR) was 37 (32-45) yrs, 39 (97.5%) were males. At HIV-1 diagnosis, median (IQR) viremia and CD4+ were 4.7 (4.3-5) Log10cps/mL and 469 (299-627) cells/µL, respectively. 27 (67.5%) pts had HIV-1 B subtype. At the enrolment, median (IQR) CD4+ was 720 (583-1041) cells/µL and RV was 3 (2-6) cps/mL. All pts were on 2 NRTI-regimen with a 3rd drug (20 INSTI, 15 NNRTI, 5 PI). A positive correlation emerged among HIV-DNA levels in the GALT and PBMC (Rho= 0.432; p=0.005), CD8+ L counts (Rho=0.367; p=0.02), and a negative correlation emerged with blood CD3+ L percentage (Rho=-0.489; p=0.006). Peripheral blood HIV-DNA values were inversely correlated with the CD4+ nadir (Rho= -0.379; p=0.017) and blood CD4+/CD8+ ratio (Rho= -0.362; p=0.022), and directly correlated with GALT CD4+CD38+ (Rho= 0.414; p=0.028) and blood CD8+CD38+ L (%) (Rho= 0.400; p=0.026). A positive correlation among GALT and peripheral blood CD4+CD38+ (Rho= 0.555; p=0.005), CD8+CD38+ (Rho= 0.417; p=0.030), and CD19+CD38+ L (Rho= 0.498; p=0.007) was found. There was no difference in HIV-DNA levels in the GALT and PBMCs according to the ART 3rd drug. In a subgroup of 20 pts the analysis of rectal tissue and blood drug concentrations showed that tissue/plasma ratio was higher in pts on Elvitegravir (EVG) and Rilpivirine (RPV) (median ratio 2.8 and 1.7, respectively) GALT and Blood HIV-DNA levels Tissue-Plasma Drug concentration Conclusion HIV-DNA from rectal GALT is a valid marker to characterize viral reservoir. The correlation of higher GALT HIV-DNA levels, CD8+ T L counts and CD4 and CD8 activation levels suggests that a greater amount of virus in the anorectal reservoir can perpetuate the inflammatory state characteristic of HIV+ pts. EVG and RPV showed higher tissue exposure than other ART regimens Disclosures All Authors: No reported disclosures.