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The synthesis of novel catalysts for the oxygen reduction reaction, by means of a fast one-pot microwave-assisted procedure, is reported herein and deeply explained. In particular, the important role of doping atoms, like sulfur and nitrogen, in Fe2O3-reduced graphene oxide nanocomposites is described to address the modification of catalytic performance. The presence of dopants is confirmed by X-ray Photoelectron Spectroscopy analysis, while the integration of iron oxide nanoparticles, by means of decoration of the graphene structure, is corroborated by electron microscopy, which also confirms that there is no damage to the graphene sheets induced by the synthesis procedure. The electrochemical characterizations put in evidence the synergistic catalysis effects of dopant atoms with Fe2O3 and, in particular, the importance of sulfur introduction into the graphene lattice. Catalytic performance of as-prepared materials toward oxygen reduction shows values close to the Pt/C reference material, commonly used for fuel cell and metal–air battery applications.

En este trabajo nos proponemos un acercamiento a ciertas representaciones de Mendoza correspondientes a los años inaugurales del siglo XIX, en diferentes formatos: “Descripción de la ciudad de Mendoza, remitida por su Diputado de Comercio don Eusevio [sic] Videla”, publicado en El Telégrafo Mercantil, Rural, Político, económico e historiógrafo del Río de la Plata, de Buenos Aires, más dos obras “literarias” de Francisco de Serra y Canals: El celo del Español y el Indiano instruido (1800), y El Perito incógnito y el Curioso aprovechado, además, un “Plano topográfico de la Ciudad de Mendoza del año 1802”, extraído de la obra de Jorge Ricardo Ponte, Mendoza, aquella ciudad de barro. Historia de una ciudad andina desde el siglo XVI hasta nuestros días (1987) y que, conforme expresa dicho autor, fue publicado por Monseñor José Aníbal Verdaguer en su Historia Eclesiástica de Cuyo en 1931. Nuestro objetivo es la reconstrucción de las representaciones en torno del paisaje/territorio mendocinos en esos textos, y la hipótesis que guía nuestro abordaje es la posibilidad de detectar en ellos una serie de tópicos y términos que darían cuenta de la "modernidad" ilustrada. En dichos estudios esperamos advertir la evolución de las ideas en relación con las representaciones de Mendoza, visibles a través de diferentes estrategias de escritura.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

In international law, a core aspect leads to the issue of the legal personality of the individual, which start to be considered specifically from mid-20th century. This was since that time the common concepts of human rights had already been worked out. The implemented international documents on human rights made it possible to come close to the solution of another equally important issue of legal personality of the individual. It should be admitted that, in the real theory of international law, this problem is not sufficiently completed, although there have already been some dramatic attempts in this direction. Even though the theme in the field of international law seems to be investigated, relating to the general concept of human rights, the problem of their relationship with the legal personality of an individual is not sufficiently discovered in international law; we set the target of defining how the study of this problem is currently under improvement integration process. Therefore, this article was aimed, first, at figured out what constitutes the basis of the legal personality of an individual. First, the article concentrated on the diverse views of scholars, and based on this, tried to find out the essence and semantic signification of each of them, as well as to determine some key elements that facilitate to define the relationship between human rights and the legal personality of an individual. Key words: individual, legal personality, human rights, concept, geopolitics.

The ribosomally produced antimicrobial peptides of bacteria (bacteriocins) represent an unexplored source of membrane-active antibiotics. We designed a library of linear peptides from a circular bacteriocin and show that pore-formation dynamics in bacterial membranes are tunable via selective amino acid substitution. We observed antibacterial interpeptide synergy indicating that fundamentally altering interactions with the membrane enables synergy. Our findings suggest an approach for engineering pore-formation through rational peptide design and increasing the utility of novel antimicrobial peptides by exploiting synergy.

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

The article examines the human rights issues, especially citizenship institute based on the experience the United Kingdom. An analysis of the scientific views of domestic and foreign scientists; reveals the problematic aspects of protecting human rights institute. In the era of globalization, the role of the human rights in solving urgent problems of human civilization is growing. In recent years, dramatic changes have occurred in the global legal system and the legal system of the UK. These changes will serve as the basis for the protection, enforcement and development of human rights. On the one hand, it is a process of integration and regionalization based on world globalization; on the other hand, domestic political and liberal reform processes in the UK. The main focus of the article is to study the legal status of individuals in the UK in the context of globalization, to develop proposals for improving the legislation on human rights in the Republic of Kazakhstan. The article provides for the disclosure of the legal status of the individual through global processes and author's interpretation of it, the legal basis for the protection of human rights, the definition of the features of the formation of human and civil rights and freedoms in the UK, proposals were made for its further development in Kazakhstan.

Laura Caruso,1 Alessia Castellino,2 Daniela Dessì,3 Leonardo Flenghi,4 Antonio Giordano,5 Adalberto Ibatici,6 Cesare Massone,7 Alessandro Pileri,8 Ilaria Proietti,9 Livio Pupo,10 Pietro Quaglino,11 Serena Rupoli,12 Pier Luigi Zinzani13,14 1Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco Di Catania, Catania, Italy; 2Department of Hematology, Santa Croce E Carle Hospital, Cuneo, Italy; 3Department of Hematology, Businco Hospital Arnas AOB, Cagliari, Italy; 4Hematology and Bone Marrow Transplantation Unit, Santa Maria Della Misericordia Hospital, Perugia, Italy; 5Department of Hematology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, Italy; 6Hematology and Transplant Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 7Dermatology Unit, Ospedali Galliera, Genova, Italy; 8Dermatology Unit, IRCCS S. Orsola-Malpighi Polyclinic, Bologna, Italy. Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy; 9Dermatology Unit”Daniele Innocenzi”, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Terracina, Italy; 10UOC Lymphoproliferative Diseases, Fondazione PTV Policlinico Tor Vergata, Rome, Italy; 11Dermatologic Clinic, Department of Medical Sciences University of Turin Medical School, Turin, Italy; 12Clinic of Hematology, Ospedali Riuniti Ancona, Ancona, Italy; 13IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; 14Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, ItalyCorrespondence: Pier Luigi Zinzani, IRCCS University Hospital of Bologna, Seràgnoli Institute of Hematology, and Department of Specialized, Diagnostic and Experimental Medicine, University of Bologna, via Massarenti 9, Bologna, 40138, Italy, Tel +39 051 2144042, Fax +39 051 2144037, Email pierluigi.zinzani@unibo.itAbstract: Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients’ symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.Keywords: cutaneous T- cell lymphoma, mycosis fungoides, Sèzary syndrome, mogamulizumab

Abstract Background Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by the young people and their parents in receiving the vaccine. This study will evaluate the effectiveness and implementation of an evidence-based healthcare provider-focused intervention (HPV PROTECT) adapted for use in pediatric oncology clinics, to increase HPV vaccine uptake among cancer survivors 9 to 17 years of age. Methods This study uses a hybrid type 1 effectiveness-implementation approach. We will test the effectiveness of the HPV PROTECT intervention using a stepped-wedge cluster-randomized trial across a multi-state sample of pediatric oncology clinics. We will evaluate implementation (provider perspectives regarding intervention feasibility, acceptability and appropriateness in the pediatric oncology setting, provider fidelity to intervention components and change in provider HPV vaccine-related knowledge and practices [e.g., providing vaccine recommendations, identifying and reducing barriers to vaccination]) using a mixed methods approach. Discussion This multisite trial will address important gaps in knowledge relevant to the prevention of HPV-related malignancies in young cancer survivors by testing the effectiveness of an evidence-based provider-directed intervention, adapted for the pediatric oncology setting, to increase HPV vaccine initiation in young cancer survivors receiving care in pediatric oncology clinics, and by procuring information regarding intervention delivery to inform future implementation efforts. If proven effective, HPV PROTECT will be readily disseminable for testing in the larger pediatric oncology community to increase HPV vaccine uptake in cancer survivors, facilitating protection against HPV-related morbidities for this vulnerable population. Trial registration ClinicalTrials.gov Identifier: NCT04469569, prospectively registered on July 14, 2020.

Abstract Detection of Zn(II) in oil-polluted seawater via square-wave anodic stripping voltammetry (SW-ASV) utilizing thin gold electrodes sputtered onto nanoporous poly(acrylic acid)-grafted-poly(vinylidene difluoride) (PAA-g-PVDF) membrane is herein reported. Prior to SW-ASV, PAA grafted nanopores demonstrated to efficiently trap Zn(II) ions at open circuit. This passive adsorption followed a Langmuir law. An affinity constant of 1.41 L $$\upmu $$ μ mol $$^{-1}$$ - 1 and a maximum Zn(II) adsorbed mass q $$_{max}$$ max of 1.21 $$\upmu $$ μ mol g $$^{-1}$$ - 1 were found. Applied SW-ASV protocol implied an accumulation step (− 1.2 V for 120 s) followed by a stripping step (− 1.2 to 1 V; 25 Hz; step: 4 mV; amplitude: 25 mV; acetate buffer (pH 5.5)). It revealed a Zn redox potential at − 0.8 V (Ag/AgCl pseudo-reference). Multiple measurements in synthetic waters close to the composition of production waters exhibited a decreasing precision with the number of readings R (1.65 $$\%$$ % (R = 2) and 6.56 $$\%$$ % (R = 3)). These membrane-electrodes should be used as disposable. The intra-batch mean precision was 14 $$\%$$ % (n = 3) while inter-batches precision was 20 $$\%$$ % (n = 15). Linear and linear-log calibrations allow exploitation of Zn(II) concentrations ranging from 10 to 500 $$\upmu $$ μ g L $$^{-1}$$ - 1 and 100 to 1000 $$\upmu $$ μ g L $$^{-1}$$ - 1 respectively. The LOD was 4.2 $$\upmu $$ μ g L $$^{-1}$$ - 1 (3S/N). Thanks to obtained calibration, a detected Zn(II) content of 1 ppm in a raw production water from North Sea oil platform was determined.

Background: Parkland Health is a 900-bed safety-net hospital that serves Dallas County, Texas. It has an OPAT program in which patients are managed via self-administration (S-OPAT), home-health/hemodialysis (H-OPAT), and skilled nursing facilities (SNF-OPAT). We evaluated the reasons for unscheduled emergency department (ED) visits by patients in these groups to identify strategies to decrease unexpected healthcare utilization and to improve safety. Methods: We performed a retrospective chart review of all adult patients discharged from Parkland Health on OPAT between April and June 2021. Demographic, medical, and healthcare utilization information, including the date and reason of first unscheduled ED visit after discharge, was collected utilizing a standardized instrument. The institutional review board approved this study. Results: In total, 184 patients were discharged with OPAT. Among them, 32% were female and 55% identified as Hispanic; 41% were non-English speakers, and 45% were treated for a musculoskeletal infection. Among all OPAT models of care, 43.4% were S-OPAT patients, 31.5% were H-OPAT patients, and 25% were SNF-OPAT patients (Table 1). The groups differed, and fewer African Americans received H-OPAT. Also, 45% were being treated for musculoskeletal infections and were more likely to be discharged with H- or SNF-OPAT. In addition, 41% were being treated for endovascular infections and 21.7% were being treated for genitourinary infections. The total length of stay in the hospital was longer for SNF-OPAT patients and shorter for S-OPAT patients (Table 2). Among 184 OPAT patients, 41 patients (22.2%) had an ED visit: 17.3% SNF-OPAT patients, 27.6% H-OPAT patients, and 21.3% S-OPAT patients (Table 2). ED visits were attributed to intravenous (IV) access–related problems (12 of 41, 29.0%), worsening of known infection (3 of 41, 7.3%), and abnormal blood test results (2 of 41, 4.9%). Also, 24 ED visits (58%) were not related to underlying infection or OPAT. However, when examined by the OPAT care model, 41% of ED visits among S-OPAT patients, 20% among H-OPAT visits, and 25% among SNF-OPAT visits were related to IV access issues. Among S-OPAT ED visits pertaining to IV access, 71% were for minor issues such as dressing changes or line occlusion or malfunction. Conclusions: One-fifth of OPAT patients had an unscheduled ED visit, of whom 20%–41% had issues with IV access. Many of these visits could be avoided with enhanced outreach to patients discharged with OPAT and improved ambulatory capabilities to provide standard services related to maintenance of IV access.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP).Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes.Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30–7.01) and 10.38 letters (95% CI = 8.02–12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from −154.99 to −109.90) and 213.93 µm (95% CI = from −280.04 to −147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2–5.6) and 2.8 injections (95% CI = 1.3–4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes.Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.

Abstract The objective of this prospective study was to investigate the morphological changes of myopic choroidal neovascularization (mCNV) after treatment with anti-vascular endothelial growth factor and to identify potential features predictive of the final BCVA. OCT and OCTA features were evaluated at baseline and at 1, 6 and 12 months. Parameters investigated were the maturity pattern, presence of mCNV OCT activity signs, subretinal fibrosis and mCNV area. Forty patients (41 eyes) were included in the study. At the final visit, after a mean of 3.1 ± 1.4 injections, BCVA had improved significantly (p = 0.009) and subretinal hyperreflective exudation, subretinal fluid and intraretinal cysts nearly disappeared at 12 months. At baseline, 20 eyes had an immature CNV that were smaller, required less injections (2.5 ± 1.2 vs 3.8 ± 1.4, p = 0.002), they completely regressed in seven eyes and achieved a better BCVA (0.14 ± 0.15 vs 0.40 ± 0.26 logMAR, p

Accelerated activation of the human plasminogen zymogen (hPg) to two-chain active plasmin (hPm) is achieved following conformational changes induced by ligand-binding at the lysine-binding sites (LBSs) in four of the five hPg kringle domains. In this manner, pattern D skin-trophic strains of Group A streptococci (GAS), through the expression of surface plasminogen-binding M-protein (PAM), immobilize surface hPg, thereby enabling rapid hPg activation by GAS-secreted streptokinase (SK). Consequently, GAS enhances virulence by digesting extracellular and tight cellular junctional barriers using hPm activity. Many studies have demonstrated the singular importance of the kringle-2 domain of hPg (K2hPg) to PAM-binding using hPg fragments. Recently, we showed, using full-length hPg, that K2hPg is critical for PAM binding. However, these studies did not eliminate any modulatory effects of the non-K2hPg LBS on this interaction. Moreover, we sought to establish the significance of the intramolecular interaction between Asp219 of the LBS of K2hPg and its serine protease domain binding partner, Lys708, to conformational changes in hPg. In the current study, selective inactivation of the LBS of K1hPg, K4hPg, and K5hPg revealed that the LBS of these kringle domains are dispensable for hPg binding to PAM. However, the attendant conformational change upon inactivation of K4hPg LBS increased the affinity of hPg for PAM by an order of magnitude. This finding suggests that the native hPg conformation encloses PAM-binding exosites or sterically hinders access to K2hPg. While simultaneous inactivation of the LBS of K1hPg, K4hPg, and K5hPg inhibited hPg/SK association alongside hPg activation, the replacement of Lys708 generated a slight conformational change that optimally accelerated hPg activation. Thus, we accentuate disparate functions of hPg LBS and conclude, using intact proteins, that K2hPg plays a central role in regulating hPg activation.

In the setting of follicular lymphoma (FL), frontline therapy with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) has represented for many years the standard of care for patients with symptomatic advanced disease. More recently, the combination of bendamustine plus rituximab (R-B) has emerged as an alternative therapeutic option. We present a retrospective, multicenter, observational study aimed at comparing outcomes and toxicities observed in 145 patients diagnosed with grade 3A FL treated with a first line therapy in 15 Italian Fondazione Italiana Linfomi centers between the 1st of January 2014 and the 30th of May 2018. Seventy patients were treated with R-B and 75 with R-CHOP. In the R-B group, the median age at the time of diagnosis was 67 years compared with 59 years in the R-CHOP group. Patients in R-B group achieved a similar overall response rate (96% vs. 99%) and a better complete remission rate (87% vs. 80%, p=0.035) compared with patients in R-CHOP group. Progression free survival (PFS) was similar between individual treated with R-CHOP and R-B (48- month PFS 77.7% vs. 76.6% respectively, p=0.745). The overall survival was significantly longer with R-CHOP treatment (HR=0.16; 95% IC, 0.04-0.74; p=0.007); however, no statistical significant difference was observed after adjustment for age. With the limitations of the study design, our results suggest that both R-B and R-CHOP seem to be valid first-line treatment options in FL3A.

We combined tenets of learning communities and place-based learning to develop an innovative first-year program for STEM students. Using a quasi-experimental design, we found that participants in the place-based learning community had a stronger sense of belonging, improved academic performance, and increased first-year persistence relative to a matched reference group. We also showed that participation narrowed equity gaps in first-year outcomes for students underrepresented in the sciences. A sense of place arises not just from a location, but from interrelationships between people and the natural world, and these results suggest organizing learning around place can promote inclusive student success.

Abstract Background Transfusion of blood products is a necessary part of successful delivery of myelosuppressive regimens in pediatric cancer. There is a paucity of literature characterizing outcomes or management of pediatric patients with cancer when transfusion is declined. Aims The objective of this paper is to describe the clinical characteristics, care, and outcomes of patients with cancer at risk for declining transfusion. Methods and Results A retrospective cohort of patients aged 0–21 years with cancer managed at Children's Healthcare of Atlanta between 2006 and 2020 and with ICD‐9 codes indicating risk of “transfusion refusal” or Jehovah's witness (JW) religion was identified. Demographics, disease, and management were abstracted. Descriptive statistics were performed to examine associations with transfusion receipt. Among 35 eligible patients identified as at risk for declining transfusion, 89% had primary guardians who identified as JW, and 45.7% identified as Black, non‐Hispanic. Only 40% of guardians actively declined transfusion. Transfusion recipients had significantly lower hemoglobin (g/dl) and platelet counts (1000/μl) at initial presentation (9.6 vs. 11.9, p

Abstract Abnormal NIPT results, contrasting with normal fetus development, could disclose maternal malignancy, and this possibility should always be explained during pretest counseling. In this case, a complete diagnostic assessment is recommended and should be managed by a multidisciplinary team to define the best timing for diagnostic procedures, delivery, and treatment.

В статье рассмотрены проблемные аспекты соблюдения и защиты прав человека на основе анализа опыта Великобритании. На сегодняшний день в эпоху глобализации возрастает роль прав человека, происходят кардинальные изменения в мировой правовой системе и правовой системе Казахстана. Эти изменения послужат основой для защиты, обеспечения и развития прав человека: с одной стороны, это процесс интеграции и регионализации, основанный на мировой глобализации, с другой - внутриполитические и либеральные реформенные процессы в Великобритании. Целью статьи является исследование правового статуса личности в Великобритании, выработка рекомендаций по совершенствованию правозащитного законодательства Республики Казахстан. При проведении данного исследования проведен анализ правового статуса личности в Великобритании; выявлены особенности механизма реализации прав и свобод человека и гражданина; рассмотрены возможности имплементации норм международного права и зарубежной практики в национальное законодательство Республики Казахстан для совершенствования института гражданства. В выводах авторами даны практические рекомендации и предложения по совершенствованию механизма защиты прав человека, на основе обобщения практики Республики Казахстан и Великобритании. Ключевые слова: права человека, свободы, гражданство, правовой статус человека, исполнение, государство.

Abstract This study presents the immobilization with aldehyde groups (glyoxyl carbon felt) of alcohol dehydrogenase (ADH) and formate dehydrogenase (FDH) on carbon‐felt‐based electrodes. The compatibility of the immobilization method with the electrochemical application was studied with the ADH bioelectrode. The electrochemical regeneration process of nicotinamide adenine dinucleotide in its oxidized form (NAD+), on a carbon felt surface, has been deeply studied with tests performed at different electrical potentials. By applying a potential of 0.4 V versus Ag/AgCl electrode, a good compromise between NAD+ regeneration and energy consumption was observed. The effectiveness of the regeneration of NAD+ was confirmed by electrochemical oxidation of ethanol catalyzed by ADH in the presence of NADH, which is the no active form of the cofactor for this reaction. Good reusability was observed by using ADH immobilized on glyoxyl functionalized carbon felt with a residual activity higher than 60 % after 3 batches.

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen that employs several secreted and surface-bound virulence factors to manipulate its environment, allowing it to cause a variety of disease outcomes. One such virulence factor is Streptolysin S (SLS), a ribosomally-produced peptide toxin that undergoes extensive post-translational modifications. The activity of SLS has been studied for over 100 years owing to its rapid and potent ability to lyse red blood cells, and the toxin has been shown to play a major role in GAS virulence in vivo. We have previously demonstrated that SLS induces hemolysis by targeting the chloride-bicarbonate exchanger Band 3 in erythrocytes, indicating that SLS is capable of targeting host proteins to promote cell lysis. However, the possibility that SLS has additional protein targets in other cell types, such as keratinocytes, has not been explored. Here, we use bioinformatics analysis and chemical inhibition studies to demonstrate that SLS targets the electroneutral sodium-bicarbonate cotransporter NBCn1 in keratinocytes during GAS infection. SLS induces NF-κB activation and host cytotoxicity in human keratinocytes, and these processes can be mitigated by treating keratinocytes with the sodium-bicarbonate cotransport inhibitor S0859. Furthermore, treating keratinocytes with SLS disrupts the ability of host cells to regulate their intracellular pH, and this can be monitored in real time using the pH-sensitive dye pHrodo Red AM in live imaging studies. These results demonstrate that SLS is a multifunctional bacterial toxin that GAS uses in numerous context-dependent ways to promote host cell cytotoxicity and increase disease severity. Studies to elucidate additional host targets of SLS have the potential to impact the development of therapeutics for severe GAS infections.

Abstract Background Immunoglobulin M multiple myeloma and Waldenström macroglobulinemia are two different hematological diseases with the common finding of an immunoglobulin M monoclonal gammopathy of unknown significance. However, clinical characteristics of the two entities can overlap. Case presentation In this report, we describe two cases of immunoglobulin M neoplasm with the same histological bone marrow presentation but with different clinical behavior, cytogenetics, and biological assessment. On the basis of comprehensive diagnostic workup, these patients were considered to have different diseases and treated accordingly with different approaches. Patient 1 (Caucasian man) presented with increased serum protein and immunoglobulin M (7665 mg/L) with an M-spike electrophoresis of 4600 mg/L. His bone marrow biopsy revealed a small-cell immunoglobulin M multiple myeloma. The result of testing for the MYD88 L265P mutation was negative, while fluorescence in situ hybridization analysis showed translocation t(11,14). A diagnosis of immunoglobulin M-κ multiple myeloma was made. Patient 1 was a candidate for bortezomib plus thalidomide and dexamethasone, followed by autologous stem cell transplant consolidation. Patient 2 (Caucasian man) showed an M-spike by protein electrophoresis (300 mg/L, 4.9%), with serum immunoglobulin M level of 327 mg/L. His bone marrow biopsy revealed immunoglobulin M-κ multiple myeloma. Computed tomography showed many enlarged lymph nodes and splenomegaly. Patient 2’s clinical features were suggestive of Waldenström macroglobulinemia, in contrast to the bone marrow biopsy results. The result of testing for the MYD88 L265P mutation was positive. Patient 2 was diagnosed with Waldenström macroglobulinemia and received rituximab, cyclophosphamide, and dexamethasone. Conclusions A correct differential diagnosis between immunoglobulin M multiple myeloma and Waldenström macroglobulinemia is a critical point in the setting of a new immunoglobulin M monoclonal gammopathy onset. These patients should undergo a complete diagnostic workup with pathological, radiological, and serological examinations to establish the diagnosis and plan the most appropriate treatment in order to improve the prognosis.

Carbon monoxide (CO) and formic acid (HCOOH) are suggested to be the most convenient products from electrochemical reduction of CO2 according to techno-economic analysis. To date, tremendous advances have been achieved in the development of catalysts and processes, which make this research topic even more interesting to both academic and industrial sectors. In this work, we report nanostructured Cu-Al materials that are able to convert CO2 to CO and HCOOH with good efficiency. The catalysts are synthesized via a green microwave-assisted solvothermal route, and are composed of Cu2O crystals modified by Al. In KHCO3 electrolyte, these catalysts can selectively convert CO2 to HCOOH and syngas with H2/CO ratios between 1 and 2 approaching one unit faradaic efficiency in a wide potential range. Good current densities of 67 and 130 mA cm−2 are obtained at −1.0 V and −1.3 V vs. reversible hydrogen electrode (RHE), respectively. When switching the electrolyte to KOH, a significant selectivity up to 20% is observed for C2H4 formation, and the current densities achieve 146 and 222 mA cm−2 at −1.0 V and −1.3 V vs. RHE, respectively. Hence, the choice of electrolyte is critically important as that of catalyst in order to obtain targeted products at industrially relevant current densities.

Abstract Background Despite favorable prognoses, pediatric patients with hematologic malignancies experience significant challenges that may lead to diminished quality of life or family stress. They are less likely to receive subspecialty palliative care (PC) consultation and often undergo intensive end‐of‐life (EOL) care. We examined “palliative opportunities,” or events when the integration of PC would have the greatest impact, present during a patient's hematologic malignancy course and relevant associations. Methods A single‐center retrospective review was conducted on patients aged 0–18 years with a hematologic malignancy who died between 1/1/12 and 11/30/17. Demographic, disease, and treatment data were collected. A priori, nine palliative opportunity categories were defined. Descriptive statistics were performed. Palliative opportunities were evaluated over temporal quartiles from diagnosis to death. Timing and rationale of pediatric PC consultation were evaluated. Results Patients (n = 92) had a median of 5.0 (interquartile range [IQR] 6.0) palliative opportunities, incurring 522 total opportunities, increasing toward the EOL. Number and type of opportunities did not differ by demographics. PC consultation was most common in patients with lymphoid leukemia (50.9%, 28/55) and myeloid leukemia (48.5%, 16/33) versus lymphoma (0%, 0/4, p = 0.14). Forty‐four of ninety‐two patients (47.8%) received PC consultation a median of 1.8 months (IQR 4.1) prior to death. Receipt of PC was associated with transplant status (p = 0.0018) and a higher number of prior palliative opportunities (p = 0.0005); 70.3% (367/522) of palliative opportunities occurred without PC. Conclusion Patients with hematologic malignancies experience many opportunities warranting PC support. Identifying opportunities for ideal timing of PC involvement may benefit patients with hematologic cancers and their caregivers.

Abstract Background Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes. Results We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes. Conclusions These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.

Abstract Background Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. Methods We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at

OBJECTIVES/GOALS: Adolescent and young adult (AYA) patients, diagnosed with cancer between 15 and 39 years of age, often have worse outcomes compared to younger children and older adults. We will characterize age differences in acuity and severity of illness at initial presentation, as a measure for health outcomes, in patients with new diagnoses of leukemia or lymphoma. METHODS/STUDY POPULATION: We will perform a single institution-based, retrospective analysis of a cohort of pediatric oncology patients at Children’s Healthcare of Atlanta (CHOA) who were diagnosed with leukemia or lymphoma from 2010 to 2018. Data will be abstracted from the CHOA medical record and cancer registry. We will construct a severity score, with one point for 1) admission to the Intensive Care Unit (ICU), 2) ICU-level requirements at admission, 3) stage IV or metastatic disease, and 4) white blood cell count over 100,000/microliter. We will associate this score with age at presentation using logistic regression models among patients overall and stratified by disease type. All regression models will adjust for confounders (e.g., health insurance, race and ethnicity, and local-area social vulnerability level). RESULTS/ANTICIPATED RESULTS: Previous literature has shown increased cancer incidence and mortality in AYAs compared to younger children. Therefore, we hypothesize that AYA patients with a new diagnosis of leukemia or lymphoma will have a higher acuity and severity of illness at presentation than younger patients. We conducted a pilot study analyzing acuity and severity of illness by age, race, ethnicity, and insurance status. Bivariate comparisons suggested patients aged 10 and older were as likely as those younger to have a severity score of more than 0 at diagnosis (OR=0.661 , 95% CI 0.43-1.01). However, this result was collapsed across all hematologic malignancies, did not encompass the entire cohort, and did not address possible confounders; we anticipate our estimates will be different taking these factors into account. DISCUSSION/SIGNIFICANCE: Our work will be the first steps in creating a validated tool to understand disease acuity and severity. By using this tool to characterize presentation by disease type and age, we will identify unmet needs prior to an initial diagnosis of cancer. Our findings inform strategies toward narrowing age disparities in outcomes for AYA hematologic cancers.

OBJECTIVES/GOALS: Racial/ethnic minoritized children experience poorer cancer outcomes, which may be driven by structural racism. We apply an index that combines segregation and neighborhood vulnerability to a pediatric oncology population and assesses its association with acuity of illness at initial presentation. METHODS/STUDY POPULATION: A retrospective analysis will be performed in a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta (CHOA) from 2010-2018 (N=1149). The sample will be linked to a structural racism index (SRI) that has been established in our prior work. We abstract data from medical records to quantify initial acuity of illness based on the need for ICU-level resources. Differences in sociodemographic characteristics will be analyzed by the SRI, using chi-squared, Student t-tests, and ANOVA where appropriate. Logistic regression models will be used to assess the association of the SRI with acuity of illness. RESULTS/ANTICIPATED RESULTS: We anticipate that relevant sociodemographic characteristics (e.g., race/ethnicity, insurance status) differ by the SRI. The CHOA Cancer Registry includes a racially and ethnically diverse group of patients: 63% of the cohort is White, 30% is Black,10% are Other, and 15% are Hispanic/Latino. Furthermore, we anticipate that pediatric patients with solid tumors living in counties with greater levels of structural racism as measured by the SRI experience an increased acuity of illness at initial presentation. DISCUSSION/SIGNIFICANCE: By applying a novel index quantifying structural racism, we will provide new information about the structural barriers patients and families face prior to a pediatric cancer diagnosis. This work will allow us to identify areas for potential interventions in this vulnerable young patient population.

Abstract Osteopoikilosis (OP) is a rare autosomal dominant sclerosing bone disease, caused by heterozygous mutations in the LEMD3 gene. It is characterised by numerous focal lamellar bone compact deposits in the spongiosa. In this case report, we describe a famliar case of OP and review the literature.

Highlights Primary GI MCL is rare. These patients tend to be treated less aggressively in the frontline setting yet have similar outcomes as those with secondary GI MCL. Less aggressive frontline treatment for primary GI MCL is reasonable given decent outcome, although it is unknown whether more aggressive treatment can result in improved outcomes.

Abstract Nitrogen-doped reduced graphene oxide is successfully synthesized and functionalized with hydroxylated copper ions via one-pot microwave-assisted route. The presence of cationic Cu coordinated to the graphene layer is fully elucidated through a set of experimental characterizations and theoretical calculations. Thanks to the presence of these hydroxyl-coordinated Cu2+ active sites, the proposed material shows good electrocatalytic performance for the oxygen reduction reaction, as evidenced by an electron transfer number of almost 4 and by high onset and half-wave potentials of 0.91 V and 0.78 V vs. the reversible hydrogen electrode, respectively. In addition, the N-doped Cu-functionalized graphene displays a superior current retention with respect to a commercial Pt/C catalyst during the stability test, implying its potential implementation in high-performance fuel cells and metal-air batteries.