Artículos de revistas: "Scaffolds 2.5D et 3D"

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Luo, En, Jun Cui, Y. Gao, Yun Feng Lin, S. S. Zhu y J. Hu. "Effect of Pamidronate on Protein Adsorption and Osteoblast Adhesion to Hydroxyapatite Bioceramics Scaffold". Key Engineering Materials 330-332 (febrero de 2007): 885–88. http://dx.doi.org/10.4028/www.scientific.net/kem.330-332.885.

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This study is to investigate the effect of PAM on protein adsorption and osteoblastic cells adhesion to HA bioceramics. PAM was immobilized on the surface of HA bioceramics for bone scaffold by chelating. The outermost layer of the specimens was analyzed by XPS and FT-IR. The protein adsorption test was performed using the 10% bovine calf serum absorbed on the specimens in vitro. The osteoblastic cells were inoculated and cultured on the scaffolds. SEM, MTT test and ALP activity test evaluated the cell attachment, proliferation and activity on the scaffolds. Characteristic peaks in XPS and FT-IR spectra indicated PAM being immobilized on the surface of the bioceramics. PAGE and 2-D DIGE results indicated that HA absorbed more acidic proteins, while PAM-HA absorbed more basic and neutral proteins.The cell culture test indicated that the cells actively proliferated on the scaffolds. There was no significant difference between the ALP activity of the cells cultured for 1d, 3d, 5d and 7d on PAM-HA and that of the controls. PAM had no obvious effect on the cytocompatibility of HA, and PAM-HA bioceramics could be used as bone scaffold with potential ability to improve osteogenesis.

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Jo, Jinhyeon y Kwang Sup Eom. "Development of a Three-Dimensional Porous Scaffold Adopting Lithiophilic Silver for a High-Performance Lithium Metal Anode". ECS Meeting Abstracts MA2022-02, n.º 64 (9 de octubre de 2022): 2319. http://dx.doi.org/10.1149/ma2022-02642319mtgabs.

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Lithium metal is the most promising candidate for a high-capacity anode in Li-ion batteries due to the highest theoretical specific capacity (3,860 mAh g-1) and the lowest redox potential (-3.04 V vs S.H.E.) [1]. However, the Li metal anode (LMA) is still challenging to be used practically due to mossy-like dendrite formation, dead Li growth, and infinite volume expansion resulting in safety hazards. Various approaches have been proposed to suppress Li dendrite growth, such as constructing an artificial solid electrolyte layer (ASEI) [2], modifying organic electrolyte [3], preparing lithiophilic substrates [4], and using a 3D scaffold [5]. Among them, introducing a 3D scaffold is one effective method to prevent Li dendrite growth due to its high surface area to greatly reduce low local current density, based on Sand’s formula [6]. Furthermore, the 3D scaffold can accommodate Li metals inside a porous structure, reducing the cell volume expansion. In fact, owing to the advantages of a 3D scaffold, a variety of 3D scaffolds based on Cu [5], Ni [7], and carbon [8] have been reported over the past several years. However, the lithium metal is preferentially deposited on the top of the 3D scaffold since the top of the bare 3D scaffolds has low diffusion resistance than the bottom of the scaffold due to the short diffusion length. As one of the solutions, introducing lithiophilic materials to the bottom of the 3D scaffold can be regarded as an effective way to induce Li nucleation inside the porous scaffold [9]. However, since morphological properties like porosity, pore size, and thickness also affect the Li deposition behaviors inside the 3D scaffold [9, 10], both factors should be considered simultaneously. Here, we propose a rational design of a 3D porous scaffold for dendrite-free LMA, adopting lithiophilic silver on a current collector. Specifically, we suggest optimal structural properties of 3D scaffolds, such as porosity, pore size, and thickness to induce the Li nucleation inside the bottom of the current collector, thereby achieving inner space Li deposition. We deposited Ag nanoparticles with 20 nm evaporation thickness by a thermal evaporation method on the commercial copper foils. (thickness ≈ 25 µm). The 3D scaffold was obtained by simple mixing and casting processes. The Cu nanoparticles (Cu NPs), silica particles, and PVdF binder were added to PP bottles at a weight ratio of 1:1:0.1, and the mixture was mixed by a high-energy ball mill. A mixed sample was cast on the copper foil and Ag coated copper foil. Cu NPs were welded by heating at 350 ℃ in a H2/Ar flow (1:1=v:v) for 2h. Afterward, silica particles were etched with 5% hydrofluoric acid (aq). As a result, porous copper scaffold (pCu) and Ag coated porous copper scaffold (AgpCu) were fabricated for Li metal anodes. The SEM images of pCu are shown in Fig. 1a, b, and c from which we can see the uniformly distributed sphere-like pore generated through the etching of silica particles. The average diameter of the formed pore is around 1 µm, which is the same as the size of silica used in the experiment. Fig. 1c presents a cross-sectional SEM image of a pCu with a thickness of ~80 µm. The deposited Li morphology is investigated by optical and SEM images in Fig. 2. When Li is deposited at 0.5 mA cm-2 for 4 mAh cm-2, shiny Li is observed on the top of the pCu in optical images (Fig. 2a). In contrast with pCu, AgpCu shows a clean brown optical image on the top without Li metals in Fig. 2c. In addition, the SEM images of Fig. 2b and d shows the morphologies of Li deposits Li on the pCu and AgpCu, respectively, indicating that a silver inside layer in AgpCu effectively induces inner deposition of Li. References [1] X.-B. Cheng et al., Chem. Rev, 117, 10403, 2017. [2] N.-W. Li et al., Adv. Mater. 28, 1853–1858, 2015. [3] X. Fan, et al., Nat. Nanotechnol. 13, 715–722, 2018. [4] K.-Y. Cho et al., Appl. Surf. Sci. 554, 149578, 2021. [5] Q. Yun et al., Adv. Mater. 28, 6932–6939, 2016. [6] R. Zhang et al., Adv. Mater. 28, 2155–2162, 2016. [7] S.-S. Chi et al., Adv. Funct. Mater. 27, 1700348, 2017. [8] C. Yang et al., Adv. Mater. 29, 1702714, 2017. [9] Yun et al., Chem. Eng. J. 430, 132897, 2022. [10] H. Song et al., Energy Stor. Mater. 36, 326–332, 2021. Figure 1

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Altrock, Eva, Carla Sens-Albert, Johann-Christoph Jann, Johanna Flach, Vladimir Ryabov, Nanni Schmitt, Alexander Streuer et al. "Comparison of Four Different Humanized Hematopoietic Niche Xenotransplantation Methods to Engraft Myelodysplastic Syndromes (MDS)". Blood 134, Supplement_1 (13 de noviembre de 2019): 4227. http://dx.doi.org/10.1182/blood-2019-128075.

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Introduction: Next generation sequencing techniques have identified a large number of MDS associated acquired molecular lesions. However, translation of these possible molecular targets into new therapeutic strategies has been lagging behind. This is also due to a lack of functional experimental models of MDS, in which new hypotheses can be evaluated pre-clinically. Xenograft models in NSG mice have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in MDS ([1] Medyouf et al., 2014, [2] Rouault-Pierre et al., 2017). The limiting factor of these models is the low engraftment of patient-derived CD34+ hematopoietic stem cells (HSCs). Efficient humanized 3D scaffolds in immune-compromised mouse models have been established, enabling to increase engraftment rates of normal and malignant hematopoiesis ([3] Reinisch et al., 2016, [4] Abarrategi et al., 2017). Therefore, we evaluated engraftment ability of IPSS low-risk, int-1 and high-risk-patient samples, in four different 3D scaffolds. Methods: Currently we transplanted samples from 10 MDS patients in parallel into NSG mice testing the following conditions: A) Intrafemoral co-injection of CD34+ HSCs and MSCs according to [1]. Subcutaneous implantation of 3D scaffolds. Gelfoam (B) and Bio-OSS (C) [4], Matrigel ossicles (D) [3] and primary human bone isolated after hip replacement, inserted with Gelfoam, preseeded in vitro with MSCs and mononuclear cells (MNCs) and injected in vivo with CD34+ HSCs 8 weeks after implantation (human bone ossicles) (E). Ossicles, bone marrow (BM), peripheral blood and spleens were analyzed 12 weeks after implantation of hematopoietic cells. Results: Gelfoam and human bone ossicles showed significantly higher hCD45+cell numbers compared to intrafemoral injection analyzed by flow cytometry. Engraftment in those two conditions was similarly robust. However, Gelfoam scaffolds showed higher percentual engraftment levels ranging up to 70% as compared to human bone ossicles ranging from 0.2% to 27%. Interestingly, we found systemic engraftment of hCD45+cells outside the injected bone fragment in the BM, peripheral blood and spleen solely in mice, which received human bone ossicles. In all other methods, hCD45+ cells could only be detected within the ossicles themselves. This result could possibly be explained due to transplantation of MNCs in this condition. That hypothesis was supported by another set of experiments using human bone ossicles (n=10), which showed that colonization of the scaffold was similar when transplanting either CD34+ cells + MSCs, MNCs+MSCs or MNCs only but systemic engraftment could only be seen in MNC transplanted mice. Conclusion: Our data show that hCD45+cells and MSCs from MDS BM were able to colonize humanized ossicle scaffolds. Gelfoam and human bone ossicles were the most promising novel methods to improve MDS xenograft models. For systemic engraftment, application of MNCs seems to be necessary. Disclosures Nolte: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

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Li, Jialang, Manila Ozhukil Valappil, Erwan Bertin y Viola Ingrid Birss. "N-Doped Nanoporous Carbon Scaffolds As Catalysts for CO₂ Reduction". ECS Meeting Abstracts MA2022-01, n.º 39 (7 de julio de 2022): 1782. http://dx.doi.org/10.1149/ma2022-01391782mtgabs.

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The need for clean energy solutions in order to significantly lower our carbon footprint is placing increasing attention on renewable energy, such as wind and solar. However, these technologies suffer from intermittency issues, thus making efficient energy storage and conversion a major requirement. One of the solutions to this problem is electrochemical CO2 reduction (CO2RR), using renewable energy to produce green fuels and chemicals. However, the reduction of CO2 is thermodynamically and kinetically unfavorable. To overcome this, the development of highly efficient and selective electrocatalysts is a key goal of CO2RR research. Carbon has been attracting interest as a promising candidate due to its high specific surface area, good conductivity, and low-cost. However, its catalytic performance is limited by the electroneutrality of the carbon atoms in the primarily graphitic lattice. In order to activate the CO2 molecules and enhance the adsorption of intermediates, a range of novel carbon catalysts has been developed, with nitrogen doping being the most common approach. The N atom has a similar size as C and thus the lattice mismatch after doping is minimal [1]. At the same time, the N atom also has a higher electronegativity than C which will break the electroneutrality of the carbon lattice and enhance the conductivity of the material [2-3]. Furthermore, N doping results in a range of N-based surface species, thus potentially allowing the tuning of the CO2RR products [4]. In this work, a novel, self-supported, nanoporous carbon scaffold (NCS) was used as the carbon substrate. The NCS is a templated, binder-free mesoporous carbon material with tunable pore sizes, a high surface area, good conductivity, and scalability [5]. Here, N doping of the NCS was achieved by heat treatment in NH3. An in house flow cell that can be switched between flow-through and flow-by modes was developed, allowing the NCS to be used as a model material to understand the impact of fluid flow on mass transfer limitations in the CO2RR and on any local pH effects that may be present. The CO2RR performance was tested in the flow cell using a CO2-saturated KHCO3 solution. The bare NCS was confirmed to generated only H2, while the N-doped NCS gives roughly a 50:50 ratio of H2:CO at all potentials, with the onset potential being ca. -0.55 V vs RHE. The effect of the NCS pore size was also investigated, showing that an NCS membrane with a nominal 85 nm pore diameter produced roughly 45% CO, while the NCS-12 (12 nm pore size) material gave somewhat more CO (ca. 55-60%). At the same time, the NCS-12 gave lower current densities, despite its higher surface area, likely due to poorer pore accessibility. Furthermore, running the cell in the flow-through mode gave higher currents at all of the NCS-based catalysts, most likely due to removal of trapped gases. Current work is focused on determining the effect of the N content and the type of N-based functionalities attached to the NCS surface on the CO2RR performance. References [1] Ji, Yan, et al. “Plasma-regulated N-doped carbon nanotube arrays for efficient electrosynthesis of syngas with a wide CO/H2 ratio.” Science China Materials 63.11 (2020): 2351-2357. [2] Liu, Weiqi, et al. “Utilizing spatial confinement effect of N atoms in micropores of coal-based metal-free material for efficiently electrochemical reduction of carbon dioxide.” Applied Catalysis B: Environmental 272 (2020): 118974. [3] Gao, Kun, et al. "Efficient metal‐free electrocatalysts from N‐doped carbon nanomaterials: mono‐doping and co‐doping." Advanced Materials 31.13 (2019): 1805121. [4] Duan, Xiaochuan, et al. "Metal‐free carbon materials for CO2 electrochemical reduction." Advanced Materials 29.41 (2017): 1701784. [5] Atwa, Marwa, et al. "Scalable nanoporous carbon films allow line-of-sight 3D atomic layer deposition of Pt: towards a new generation catalyst layer for PEM fuel cells." Materials Horizons 8.9 (2021): 2451-2462.

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Roh, Terrence, Ying Chen, Harry Paul, Chengchen Guo y David Kaplan. "P140 3D BIOENGINEERED TISSUE MODEL OF THE LARGE INTESTINE TO STUDY INFLAMMATORY BOWEL DISEASE". Inflammatory Bowel Diseases 26, Supplement_1 (enero de 2020): S34—S35. http://dx.doi.org/10.1093/ibd/zaa010.087.

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Abstract An in vitro model of intestine epithelium with an immune compartment was bioengineered to mimic immunologic responses seen in inflammatory bowel disease [1]. While aspects of intestinal immunity can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelium comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy silk scaffolds. Confluent epithelial monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon γ resulted in morphology changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines associated with active inflammatory bowel disease, including CXCL10, IL-1β, IL-6, MCP-2, and MIP-1β. The macrophage layer enhanced epithelial and biochemical responses to inflammatory stimuli, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease. References: 6 Roh, T.T., et al., 3D bioengineered tissue model of the large intestine to study inflammatory bowel disease. Biomaterials, 2019: p. 119517. 7 In, J., et al., Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cellular and molecular gastroenterology and hepatology, 2015. 2(1): p. 48–62.e3. 8 Chen, Y., et al., In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS ONE, 2017. 12(11): p. e0187880. Colonoid and macrophage cultivation scheme in the 3D bilayer system. (A) Human monocytes were isolated from whole blood and human colonoids from large intestine biopsies were cultured according to established protocols [2]. (B) Cell suspensions of colonoids were seeded on the film surface on the inner silk scaffold and monocyte-derived macrophages were seeded throughout the porous outer silk scaffold using established protocols [3]. (C) The model is cultured for 3 weeks total with 2 weeks in High WNT media and 1 week in differentiation media based on established protocol. Colonoids are present in the model throughout the 3 week culture time. 2 sets of macrophages are added with the first set added after the first week of culture and the second set replacing the first set after the second week.

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Reisner, Erwin. "(Keynote) Reversible CO2 Reduction Electrocatalysis in Solar-Powered Chemistry". ECS Meeting Abstracts MA2023-02, n.º 52 (22 de diciembre de 2023): 2517. http://dx.doi.org/10.1149/ma2023-02522517mtgabs.

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Semi-artificial photosynthesis interfaces biological catalysts with synthetic materials such as electrodes or light absorbers to overcome limitations in natural and artificial photosynthesis. The benefit of using biocatalysts in electrocatalytic CO2 reduction is their electrochemical reversibility that enables their operation at very low overpotentials with high selectivity. This presentation will summarise my research group’s progress in integrating the CO2 reducing enzyme formate dehydrogenase into bespoke hierarchical 3D electrode scaffolds and the exploitation in solar-powered catalysis. I will present the electrochemical features and characterisation of the biocatalyst-material interface and provide my team's understanding of the electrochemical properties of the immobilised formate dehydrogenase. This insight allows the wiring of the biocatalyst into electrocatalytic schemes, photoelectrochemical devices and photocatalytic systems for unique CO2 utilisation reactions. The fundamental insights gained by integrating isolated formate dehydrogenase in electrodes will be presented and the case be made that this enzyme allows opening a solar-to-chemical conversion space that is currently not accessible with purly synthetic or biological catalysts (see uploaded Image as example). Recent publications: (1) Lam et al., Angew. Chem. Int. Ed., 2023, in print. (2) Bhattacharjee et al., Nat. Synth., 2023, 2, 182-92. (3) Badiani et al., J. Am. Chem. Soc., 2022, 144, 14207-16. (4) Cobb et al., Nat. Chem., 2022, 14, 417-24. (5) Edwardes Moore et al., Proc. Natl. Acad. Sci. USA, 2022, 119, e2114097199. (6) Anton Garcia et al., Nat. Synth. 2022, 1, 77-86. Reviews: (1) Fang et al., Chem. Soc. Rev., 2020, 49, 4926–52. (2) Zhang & Reisner, Nature Rev. Chem., 2020, 4, 6–21. (3) Kornienko et al., Acc. Chem. Res., 2019, 52, 1439–44. (4) Kornienko et al., Nature Nanotech., 2018, 13, 890–99

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Bradley, M., L. Baldinger, M. Bhatia, J. Garvin, D. George, E. Roman, P. Satwani, P. L. Martin, J. Kurtzberg y M. S. Cairo. "A pilot study of myeloablative (MA) autologous stem Cell (Auto SCT) followed by reduced intensity (RI) allogeneic transplantation (AlloSCT) in children with relapsed/refractory(R/R) Hodgkin’s disease (HD)". Journal of Clinical Oncology 25, n.º 18_suppl (20 de junio de 2007): 20007. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.20007.

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20007 Background: Allo SCT may benefit patients with R/R HD by providing a graft vs lymphoma effect. Peggs et al (Lancet 2005) demonstrated durable engraftment and reduced non relapse mortality (NRM) in HD pts post RI Allo SCT. Carella et al (JCO2000) and Gutman et al (BMT2005) demonstrated the success of MA Auto SCT followed by RI AlloSCT in adults with refractory lymphoma. We investigated the feasibility of MA Auto SCT followed by RI Allo SCT in children with R/R HD. Methods: MA conditioning prior to AutoSCT was CTX 1,500 mg/m2 x 4 d, BCNU 100 mg/m2 x 3d, VP-16 800 mg/m2 x 3d. AlloSCT conditioning was fludarabine 30 mg/m2 x 5d, busulfan 3.2 mg/kg x 2d, and R ATG 2 mg/kg x 4d (unrel. donor). CD20+ patients received rituximab (375 mg/m2/wk x4) and all pts received involved field radiotherapy (IFRT). Results: Ten pts have enrolled, 2 pts did not proceed (parental withdrawal) to RI AlloSCT (Donors: 1 MRD, 2 MUD, 5 UCB). Median time to RI AlloSCT after MA Auto SCT was 142 d (97–219). The median cell dose was 3.43 x 107 TNC/kg for UCB grafts (n=5). Engraftment was achieved at a median of 20.5 d for PMN and 46.5 d for PLT. Donor chimerism reached ≥ 95% in all pts by day 100 with a median follow up of 703d (128–2025). Toxicities were grade (3) hematuria (n=1), (3–4) infection (n=7), (4) pulmonary fibrosis (n=1), (4) hearing loss (n=1), (4) neurotoxicity (n=1). GVHD: grade II-III aGVHD (3/8), cGVHD (3/8). Six patients are alive and NED post allo SCT. There has been one NRM (cGVHD) and one relapse mortality. The OS at one year is 66.7%. Conclusions: MA AutoSCT followed by RI AlloSCT is feasible and well tolerated in pediatric pts with R/R HD. A larger study with longer follow up is required to determine if this approach will reduce relapse, long term toxicity and/or improve survival. No significant financial relationships to disclose.

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Setiawan, Deni. "Kajian Pembelajaran BIM di Perguruan Tinggi". Jurnal Civronlit Unbari 7, n.º 1 (27 de abril de 2022): 43. http://dx.doi.org/10.33087/civronlit.v7i1.96.

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BIM diketahui memiliki banyak manfaat yang dapat mempermudah pekerjaan perencanaan maupun evaluasi dari suatu proyek konstruksi. Manfaat ini dapat memberikan pandangan yang menyeluruh untuk membantu klien maupun pemilik proyek sebelum melakukan tahapan pelaksanaan untuk mengurangi risiko yang akan terjadi. Penggunaan BIM dapat membuat pekerjaan lebih efisien. Salah satu upaya pemerintah untuk mensosialisasikan penggunaan BIM yaitu dengan menerapkan BIM sebagai kompetensi keahlian di tingkat SMK. Hal ini untuk meningkatkan jumlah tenaga kerja yang telah paham mengenai konsep BIM. Zhabrinna, et, al (2018) menyatakan jumlah tenaga ahli di Indonesia yang berkompeten dalam menerapkan BIM masih terbilang rendah. Tujuan makalah ini adalah mengkaji pembelajaran BIM di Perguruan Tinggi. Penelitian ini mengambil pembelajaran BIM di tingkat Program Studi Teknik Sipil Universitas Kristen Maranatha sebagai studi kasus. Pembelajaran BIM (3D) di Teknik Sipil Universitas Kristen Maranatha dilakukan pada 2 matakuliah CE214-Komputer Grafis&Struktur Bangunan 1 dan 2. Pembelajaran BIM (4D) dilakukan pada matakuliah CE600- Manajemen Proyek. Pembelajaran BIM (5D) dilakukan pada 2 matakuliah CE600- Manajemen Proyek dan CE832-Introduction Buliding Information Modelling. Pembelajaran BIM di tingkat perguruan tinggi di Indonesia sangatlah dibutuhkan untuk memenuhi permintaan dunia konstruksi di era industri 4.0. Teknik Sipil Universitas Kristen Maranatha sudah memulai untuk mengintegrasikan proses pembelajaran BIM ke dalam beberapa mata kuliah dapat dinilai baik karena dibuktikan dengan angka keberhasilan yang cukup tinggi pada saat mahasiswa mengambil ujian sertifikasi.

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D'Angelo, Sandra P., Mihaela Druta, Brian Andrew Van Tine, David A. Liebner, Scott Schuetze, Aisha N. Hasan, Andrew P. Holmes et al. "Safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794) in advanced myxoid/round cell liposarcoma (MRCLS) following high lymphodepletion (Cohort 2): Interim analysis." Journal of Clinical Oncology 39, n.º 15_suppl (20 de mayo de 2021): 11521. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.11521.

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11521 Background: Cancer testis antigen NY-ESO-1 is expressed in multiple tumor types, including 80‒90% of MRCLS [1,2]. Overall response rates (ORRs) to MRCLS treatment are low (1L, <20%; 2L, <10%) [2]. Lete-cel, an autologous T-cell therapy, targets NY-ESO-1/LAGE-1a+ tumors using a genetically modified, high-affinity T-cell receptor. High-dose lymphodepletion (LD) was linked with better responses in synovial sarcoma [3]; the current study tested this hypothesis in MRCLS. Methods: This open label, pilot study evaluates lete-cel efficacy and safety in advanced MRCLS following low-dose (Cohort 1 [C1]; 30 mg/m2 fludarabine [flu] x 3d + 600 mg/m2 cyclophosphamide [cy] x 3d) or high-dose (Cohort 2 [C2]; 30 mg/m2 flu x 4d + 900 mg/m2 cy x 3d; initiated based on C1 data) LD. Key eligibility: age ≥18 y; HLA-A*02:01; A*02:05, or A*02:06; advanced high-grade NY-ESO-1+ MRCLS (≥30% of cells 2+/3+ by IHC); prior anthracycline; measurable disease; specified washouts; and active/chronic/intercurrent illness restrictions. Stages include screening, leukapheresis, lete-cel manufacture, LD, lete-cel infusion (1– 8 × 109 transduced T cells), follow-up. Response is assessed at wk 4, 8, 12, and 24, then every 3 mo to disease progression/death/withdrawal. The primary efficacy endpoint is investigator-assessed ORR by RECIST v1.1. In C1 (n=10 patients [pts]), lete-cel was well tolerated and linked with 2 confirmed partial responses (PR; ORR, 20%) and stable disease (SD) in 8 pts. Planned interim analysis for C2, shown here, was done once all 10 treated pts had ≥3 post-baseline disease assessments or progressed/died/withdrew. Efficacy data will be correlated with transduced cell kinetics and pharmacodynamics marker profiles. Results: Durable (1.0–7.8 mo) PR (4/10 pts [ORR, 40%]; 2 ongoing) and prolonged (2.7–10.6 mo) SD (5/10 pts; 3 ongoing) with tumor regression were observed. Treatment-emergent cytopenias occurred in all pts. All experienced T-cell related cytokine release syndrome (5 serious adverse events; 30% Grade 3), with onset ≤5d of infusion and median duration 7.5d. Graft-vs-host disease, immune effector cell–associated neurotoxicity syndrome, pancytopenia, or aplastic anemia were not reported. Conclusions: A single lete-cel infusion after high LD showed antitumor activity in advanced MRCLS and a manageable safety profile consistent with other lete-cel studies. The trial is active but no longer recruiting (NCT02992743). MRCLS is included in a separate, ongoing lete-cel study (NCT03967223). References: 1. D’Angelo SP, et al. J Clin Oncol 2018;36:15_suppl, 3005. 2. Pollack SM, et al. Cancer Med 2020;9(13):4593–602. 3. D’Angelo SP, et al. J Immunother Cancer 2020;8:P298. Funding: GSK (208469; NCT02992743). Editorial support was provided by Eithne Maguire, PhD, of Fishawack Indicia, part of Fishawack Health, and funded by GSK. Clinical trial information: NCT02992743.

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Haselager, Marco, Eduard Perelaer, Arnon P. Kater y Eric Eldering. "Development of a Novel Lymph Node-Based 3D Culture System Promoting Chronic Lymphocytic Leukemia Proliferation and Survival". Blood 136, Supplement 1 (5 de noviembre de 2020): 47–48. http://dx.doi.org/10.1182/blood-2020-141962.

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INTRODUCTION. Primary chronic lymphocytic leukemia (CLL) cells, despite originating from a proliferative disease, rapidly undergo apoptosis in vitro in absence of microenvironmental survival signals1. Although co-culture with stromal cells or the addition of soluble factors can increase and extend CLL survival, no system permits the long-term expansion of CLL cells in vitro2. The difficulties of mimicking a physiologic microenvironment supporting CLL cells hinder in vitro studies of proliferation, drug screens and prevent propagation of rare subclones. For other cancers, various types of 3D cultures have been introduced utilizing scaffolds, gels, spheroid cultures and fluidic systems, representing a more accurate representation of the in vivo microenvironment3. Unlike solid tumors, secondary lymphoid tissues where CLL cells proliferate in vivo, do not derive from a single stem cell progenitor. Developing an appropriate 3D in vitro culture system for CLL is of obvious importance and may contribute pathophysiological relevance to study long-term CLL proliferation and more accurate drug screening4,5. Within the field of CLL, attempts have focused on bone marrow stroma, but it may be biologically and clinically more relevant to investigate the lymph node niche as this is the critical site of CLL proliferation6. METHODS. Primary CLL cells were cultured in various 3D systems including hydrogels, hanging drop cultures and ultra-low attachment plates (ULA) plates in parallel to an optimal 2D system, consisting of the culture of primary CLL cells on a monolayer of CD40L-presenting fibroblasts (3T40) or 3T3 negative control fibroblasts. CLL cells were either cultured as PBMCs alone, with or without T cells, or co-cultured with 3T40 or primary lymph node fibroblasts. CLL cells were either stimulated directly with IL-2, IL-15, IL-21 and CpG and/or indirectly via a T cell stimulation of anti-CD3/CD28. RESULTS. After testing and comparing multiple systems for the in vitro culture of CLL cells, we optimized a novel CLL culture system utilizing ULA plates creating spheroids of PBMCs isolated from peripheral blood. Without the addition of soluble factors or stroma, primary CLL cells in the ULA 3D model could be maintained in culture for 6 weeks as opposed to 1 week in the 2D system. Aside from significantly promoting CLL survival, cultures could be expanded approximately 3-4-fold over a course of 6 weeks using the ULA 3D model. 3D cultures showed a more consistent and significantly increased CLL proliferation compared to 2D cultures, independent of IGHV mutation status, increasing the average proliferation index of 2.87 to 3.90 (n=10). Additionally, co-culture with LN-derived stromal cells further increased CLL proliferation, reaching a maximum of 8 generations (n=6) (Figure 1). Lastly, when PBMCs were stimulated with IL-2, IL-15, IL-21 and CpG, spheroids developed proliferation center-like structures after 4 weeks of culture. CONCLUSIONS. We established a lymph node-based 3D in vitro culture system for CLL leading to increased CLL proliferation and survival compared to 2D systems. The set-up allows long-term expansion of CLL cells in vitro, as well as formation of proliferation center-like structures. We are currently optimizing drug resistance studies, expansion of specific CLL subclones and performing competition experiments. References: 1. Hamilton et al., Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells, 2012. 2. Asslaber et al., Mimicking the microenvironment in chronic lymphocytic leukaemia - where does the journey go?, 2013. 3. Gurski et al., 3D Matrices for Anti-Cancer Drug Testing and Development, 2010. 4. Nunes et al., 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs, 2019. 5. Aljitwai et al., A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of leukemia cells, 2014. 6. Van Gent et al., In vivo dynamics of stable chronic lymphocytic leukemia inversely correlates with somatic hypermutation levels and suggest no major leukemic turnover in bone marrow, 2008. Disclosures Kater: Genentech: Research Funding; Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Eldering:Celgene: Research Funding; Janssen: Research Funding; Genentech: Research Funding.

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Lee, Je-Hwan, Young-Don Joo, Jung-Hee Lee, Hawk Kim, Sung Hwa Bae, Min Kyung Kim, Dae Young Zang et al. "A Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in the Induction Chemotherapy for Acute Myeloid Leukemia: An Interim Analysis". Blood 120, n.º 21 (16 de noviembre de 2012): 3628. http://dx.doi.org/10.1182/blood.v120.21.3628.3628.

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Abstract Abstract 3628 Introduction: We conducted a randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults with acute myeloid leukemia (AML) and showed intensification of induction therapy using a high daily dose of daunorubicin (90 mg/m2/d × 3d) improved both complete remission (CR) rate and survival duration compared to standard daunorubicin dose (45 mg/m2/d × 3d) (Lee JH et al. Blood 2011;118:3832). Our results confirmed the ECOG work (Fernandez HF et al. N Engl J Med 2009;361:1249). Thus, high-dose daunorubicin (90 mg/m2/d) for 3 days should be the future standard of care for induction of patients with AML. However, it is not known whether a dose of 90 mg/m2/d is superior to a dose of 45–90 mg/m2/d. It is also necessary to compare the effects of high-dose daunorubicin with that of other agents, especially idarubicin. For these reasons, we began another randomized trial comparing two induction regimens in young adults with AML: idarubicin vs. high-dose daunorubicin. This study is now recruiting patients (ClinicalTrials.gov #NCT01145846). Here, we present the results of interim analysis of the study. Methods: This study began on May 2010 and target number of patient's accrual is 300. A total of 161 patients (65 years or younger) with newly diagnosed AML except acute promyelocytic leukemia were registered in this study as of March 22, 2012. Four patients were removed from the study (patient's refusal to be randomized in 2 and change of diagnosis in 2) and the remaining 157 patients were analyzed. After random assignments, 81 patients received idarubicin (AI, 12 mg/m2/d × 3d) and 76 patients received high-dose daunorubicin (AD, 90 mg/m2/d × 3d) in addition to cytarabine (200 mg/m2/d × 7d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of idarubicin (AI, 12 mg/m2/d × 2d) or daunorubicin (AD, 45 mg/m2/d × 2d) plus cytarabine (5d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 × 6 doses) in patients with good- or intermediate-risk cytogenetics and 4 cycles of cytarabine (1 g/m2 × 6d) plus etoposide (150 mg/m2 × 3d) in those with high-risk cytogenetics. Hematopoietic cell transplantation (HCT) was performed according to attending physician's discretion. Results: CR was induced in 123 (78.3%) of 157 patients. Reasons for induction failure were resistant disease in 26, hypoplastic death in 2, and indeterminate cause in 6. As postremission therapy, 3 patients received no further treatment, 35 received consolidation chemotherapy without HCT, 73 underwent allogeneic HCT, and 12 underwent autologous HCT. The CR rates were not significantly different between two arms: 77.8% (63 of 81, AI) vs. 78.9% (60 of 76, AD) (P=0.859). With a median follow-up of 285 days, overall survival probabilities at 18 months were 65.6% in AI vs. 72.6% in AD (P=0.278). The probabilities at 18 months for relapse-free survival were 78.5% in AI vs. 86.2% in AD (P=0.563) and those for event-free survival were 61.5% in AI vs. 67.7% in AD (P=0.078). Toxicity profiles were similar between two arms. Conclusions: The results of interim analysis of this ongoing phase 3 trial, which compares idarubicin (12 mg/m2/d × 3d) with high-dose daunorubicin (90 mg/m2/d × 3d), did not show significant differences in the outcomes of patients. It appears that the effects of two drugs with the doses in current study are equivalent as an induction chemotherapeutic agent in regards to CR rates and overall, relapse-free or event-free survivals. Disclosures: No relevant conflicts of interest to declare.

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Vaiselbuh, Sarah Rivkah, Houman Khalili, Annette Lee, Peter Gregersen, Jeffrey Michael Lipton y Johnson M. Liu. "Pediatric Leukemia-Specific miRNA Expression Profiles Induced by the Leukemic Stem Cell Niche". Blood 116, n.º 21 (19 de noviembre de 2010): 942. http://dx.doi.org/10.1182/blood.v116.21.942.942.

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Abstract Abstract 942 Background: Emerging evidence suggests that microRNAs (miRNAs) are critical in cancer and adult leukemia by functioning as tumor suppressors and/or oncogenes. Zhang et al identified 32 pediatric acute myeloid leukemia (AML)-specific miRNA patterns by analysis of bone marrow (BM) samples (1). They also established potential miRNAs as biomarkers for predicting CNS-relapse in pediatric acute lymphocytic leukemia (ALL). Altered miRNA expression disrupts normal hematopoiesis and might play a role in niche-induced oncogenesis. Dysfunction of mesenchymal stromal cells induces formation of myeloid sarcomas that infiltrate in the surrounding tissues (2). Previously, we described that mesenchymal stem cells (MSC) of the BM microenvironment participate in leukemic stem cell regulation in an in vivo model of the childhood AML stem cell niche(3). These human MSC niches, created in ectopic bioengineered 3D scaffolds, supported leukemogenesis in NOD/SCID mice. Pediatric AML engrafted at 1 month in the MSC-coated scaffolds in the mice and was retained in the niche up to 4 months, after which distant seeding to murine BM, liver and spleen occurred. The bioengineered niche created a sanctuary for quiescent leukemia cells and at 4 months the AML cells exited the niche and spread hematogenously, mimicking leukemia relapse. Analysis of miRNA patterns in our leukemia niche model could provide novel directions for individual risk-adapted therapy in childhood leukemia. Objective: To analyze miRNA expression patterns of pediatric AML after exposure to the niche microenvironment at different time points. Design and Method: miRNAs were obtained from primary CD34+ selected AML cells at (d0) Day0= no niche exposure, (1Mo) 1 month =niche engraftment, (4Mo) 4 months=hematogenous spread with leukemic exit from the niche. miRNAs were isolated from single cell suspensions with the mirVana miRNA isolation kit (Ambion) and analyzed on an Ilumina MicroRNA Expression Profiling single Beadchip (#RNA probes = 1145). Results: 498/1145 miRNAs expression profiles were selected with a detection p value < 0.00001. Out of 498 miRNAs expressed in the leukemic niche model, 23 were previously described as AML-specific miRNAs (2). 10/23 miRNAs were significantly upregulated and 13/23 were downregulated. Pediatric AML-specific miRNAs – miR100 and miR125b had high expression profile at baseline, but were down regulated upon contact with the niche. AML miR195 and miR193a had low expression at baseline, but miR195 was upregulated on engraftment while miR193a only upregulated at the time of hematogenous spread (niche exit). CNS-relapse in ALL might represent a physiological mechanism of leukemic exit of dormant cells from the niche sanctuary. Consistent with this notion, the same expression profile that was found in CNS-relapse in ALL patients (miR198 up – miR551a downregulated) was seen in our model when AML cells became invasive and exited the niche at 4 months. Conclusion: (1) Zhang et al. 2009, PloSOne, 4, p1 (2) Raaijmakers et al. 2010, Nature, 464, p852 (3) Vaiselbuh et al, 2010, Tissue Eng Part C Methods, June 29 (ePub) Disclosures: No relevant conflicts of interest to declare.

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Quiroga, Josué, Omar Flor, Santiago Solórzano y José Calahorrano. "Design of a Videolaryngoscope with sensor and pressure alert". Athenea 2, n.º 3 (7 de marzo de 2021): 21–27. http://dx.doi.org/10.47460/athenea.v2i3.13.

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This work presents the design and construction of a laryngoscope model with camera vision that has a vibrating device to alert the medical specialist when the force exerted causes possible damage to the patient's airway during the intubation process. Design and fabrication considerations are described using Cast Material Position (FFD). The design is validated with the use of a high-fidelity simulator, the performance is compared with commercial models and the criteria of specialists are taken into account to improve all the necessary aspects. The model presented a great functional advantage, providing greater patient safety, reducing the risk of exposure of the internal tissue to high forces in the intubation process, facilitating clinical processes for health personnel. Keywords: Video laryngoscope, intubation, 3d printer, PLA. References [1]D, Freitas. “Prototipo De Videolaringoscopio: Wi-Mac-Multivision”. Revista Chilena De Anestesia. Volumen (49), número (2), páginas (262-270), 2020. [2]G, Velázquez. “Videolaringoscopio Artesanal Macintosh”. Anestesia en México. Volumen (28). Número (1). Abril 2016. [3]R, Cooper. J, Pacey. M, Bishop. S, McCluskey. “Early clinical experience with a new videolaryngoscope (GlideScope) in 728 patients”. Can J Anaesth. Volumen (52), número (2), Feb 2005. [4]C, Billington. P, Kearns. R, Kirkbride. K, Mackintosh. C, Reeve. et al. “A comparison of McGrath and Macintosh laryngoscopes in novice users: a manikin study”. Anaesthesia. Volumen (64), número (11), Nov 2021. [5]A, Jungbauer. M, Schumann. V, Brunkhorst. A, Börgers, H, Groeben. “Expected difficult tracheal intubation: a prospective comparison of direct laryngoscopy and video laryngoscopy in 200 patients”. Br J Anaesth. Volume (102), number (4), April 2009. [6] A, Caño. M, De la Cruz. “Diseño, ingeniería, fabricación y ejecución asistidos por ordenador en la construcción: evolución y desafíos a futuro”, Informes de la Construcción. Volume (59), number 505, pag 53-71, marzo 2007. [7]V, Mazzanti. L, Malagutti. F, Mollica. “FDM 3D Printing of Polymers Containing Natural Fillers: A Review of their Mechanical Properties”. Polymers. 28 jun 2021. [8]K, Howard. Y, Huang. R, Matevosian. M, Kaplan. R, Steadman. “Video-assisted instruction improves the success rate for tracheal intubation by novices”. Br J Anaesthesia. Volume (101), number(4):568–572. Oct 2008. [9]S, Maya. “Role of video laryngoscopes in anesthesia practice”. Revista Mexicana de Anestesiología. Volume (35). Number (1), 344-361, Jun 2012. [10]M, Kaplan. D, Ward. G, Berci. “A new video laryngoscope-an aid to intubation and teaching”. J Clin Anesth. Volume (14), number (8), 620-626. Dec 2002. [11]D, Cabrera. G, Massano. S, Fernandez. S, Chaile. et al. “Video-laringoscopio de bajo costo desarrollado con tecnología de impresión 3D”, Revista Chilena de Anestesia, volumen (47), numero 4, 2018. [12]N, Perez. A, Sanchez. M, Guagliano. M, Villanueva. “HISOPOS, LARINGOSCOPIOS Y AEROSOL BOX-IMPRESIÓN 3D COVID-19”, Ministerio de Ciencia, Tecnología e Innovación-Argentina. 2020. [13]K, Yoontae. E, Lee. A,Davydov. S, Frukhbeyen. J. Seppala. S, Takagi. L, Chow and S, Alimperti. 3Dprint.com, “Biofabrication of 3D printed hydroxyapatite composite scaffolds for bone regeneration”. 30 nov 2020.

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Khazaka, Rami, Brendan Marozas, Wonjong Kim y Michael Givens. "Low Temperature Selective Epitaxy of Group-IV Semiconductors for Nanoelectronics". ECS Meeting Abstracts MA2022-02, n.º 32 (9 de octubre de 2022): 1187. http://dx.doi.org/10.1149/ma2022-02321187mtgabs.

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Continuous improvement of device performance is becoming very challenging as the transistor dimension approaches the physical limits of scalability. In particular, the source/drain (S/D) layer resistivity and contact resistance at the S/D region became major components for further parasitic resistance reduction [1]. Therefore, layers with high active doping concertation is required for future technology nodes. From another side, novel architectures such as 3D-stacked devices constraints the allowed thermal budget for epitaxy processes [2]. In this work, we will review our recent achievements on LT epitaxy for both Si:P and SiGe:B layers to enable (i) parasitic resistance reduction and (ii) novel integration schemes. All layers were grown in a 300 mm ASM reduced pressure chemical vapor deposition reactor on Si(001) substrates and patterned substrates. Firstly, we will discuss the benefits of SiP growth at low temperature leading to high active doping concentrations (~1.1×1021 cm-3), as reported in our previous work [3]. Figure 1 shows the omega-2theta scans around the symmetric (004) reflections of the Si:P/Si stacks. As expected, reducing the Si precursor flow leads to a higher substitutional P (~7.5%) incorporation in the layer. The good crystallinity of the SiP layer is attested by the well-defined thickness fringes. Figure 2a represents the XRR scans of non-selective SiP process and selective SiP process compared to 100 nm bare SiO2 on Si substrate. The presence of fringes (red curve) indicates that a 2D amorphous SiP layer is deposited on SiO2. To confirm the full selectivity of the process and the absence of nuclei on the SiO2 surface, top view SEM was performed (cf. Figure 2b). Afterwards, we will focus on the SiGe:B epitaxy at low temperature. Figure 3a shows omega-2theta scans around the symmetric (004) reflections of the SiGe:B/Si stacks for various B flows. The apparent Ge content drops from 52.1% to around 41.3% when B flow was multiplied by 16. The inset represents the reciprocal space map (RSM) around the asymmetric (224) peak of SiGe:B layers grown on Si(001) substrates with the highest B flow. The RSM clearly indicates high quality and fully strained SiGe:B layer. Figure 3b depicts the apparent Ge drop vs B flow. This reduction in Ge content is attributed to B strain compensation effect leading to artificially lower Ge content [4]. Figure 3c represents SiGe:B layer resistivity vs B flow. Resistivity drops until a critical B flow and then increases with increasing B flow. Figure 4 shows active doping concentration and Hall mobility as function of the B flow. The Hall measurements were performed on a cleaved wafer edge and assume a Hall scattering factor of 1. Active carrier concertation increases with increased B flow. As a side effect of the higher activation, the Hall mobility is lowered likely due to an increase in ionized impurity scattering which is the reason why the resistivity does not decrease substantially below a certain value for higher B flows at current growth conditions. Layers with similar physical properties have resulted in S/D metal contact resistivity of ~5×10-10 Ohm.cm2 [5]. Figure 5 depicts the selective process on advanced patterned nanosheet test structures. Figure 5a illustrates the selectivity towards several nanosheet structures, Figure 5b shows a zoomed in image indicating selective process towards inner SiN spacers and SiO2. Figure 5c is a FFT of the SiGe:B area indicated by red square and Figure 5d is an EDS map of the key elements (Si, Ge, O, C, Cl, F, N). Figure 6a and 6b show the selective process stability over 20 runs. The HR-XRD measurements at wafer center are represented in Figure 6a. Figure 6b represents the resistivity at the wafer center. Thickness uniformity across one of the wafer is illustrated in Figure 6c. The results indicate excellent wafer to wafer and within wafer uniformities despite low temperature processing. LT epitaxy offers several advantages to reach high active doping concentrations and enable novel integration schemes. Despite challenges associated to LT epitaxy, in this work we showed the possibility to grow selective layers while maintaining the excellent physical layer properties, within wafer uniformity and wafer to wafer reproducibility. [1] H. Wu et al. EEE International Electron Devices Meeting (IEDM), (2018), pp. 35.4.1. [2] A. Vandooren et al. IEEE Symposium on VLSI Technology, (2018), pp. 69-70. [3] R. Khazaka et al. ECS Meeting Abstracts, MA2020-02(24), (2020) 1734-1734. [4] J.M. Hartmann et al. ECS JSST, 3(11) (2014) 382. [5] H. Xu et al. IEEE Symposium on VLSI Technology, (2022), (to be published). Figure 1

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Lin, Chi Hua Sarah, Beth Shaz y Rona Singer Weinberg. "Low Dose Umbilical Cord Blood Transplant Results in Skewed Immune Cell Composition Which May Impact Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation". Blood 132, Supplement 1 (29 de noviembre de 2018): 5672. http://dx.doi.org/10.1182/blood-2018-99-111541.

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Abstract Introduction Reconstitution of donor-derived immune system after allogeneic hematopoietic stem cell transplantation (HSCT) is essential for recovery and long-term survival. Despite routine use of human umbilical cord blood (hUCB) as a stem cell source for allogeneic HSCT, much remains unknown regarding the kinetics of immune recovery and correlation with different transplant cell dosages. To study the hUCB repopulating potential, different hUCB CD34+ cell dosages were transplanted into immune deficient NSG mice; hematopoietic cells were then collected and engraftment was analyzed. Methods NOD/SCID/IL-2Rγnull recipient (NSG) mice (Jackson Laboratories, Bar Harbor, ME) were kept in pathogen-free facilities. CD34+ cells were isolated from a pool of six hUCB donors using a CD34+ microbead kit (Miltenyi Biotec). Each sublethal irradiated (220 or 300 cGy) 8 week old female NSG mice received either low dose (15x103, N=15) or high dose (75x103, N=15) CD34+ cells transplanted intravenously via retro-orbital route. Animal experiments were performed in accordance with Institutional Animal Care and Use Committee guidelines. Statistical analysis was performed with Prism software (GraphPad Software, Inc) and Excel. Data are presented as mean ± standard error of the mean (SEM). Results To determine the effects of hUCB CD34+ cell dosages on the rate of engraftment, NSG mice were transplanted with low doseor high dose CD34+ cells. The transplanted CD34+ cell dosages were comparable to clinical dosages based on body weight (Mavroudis et al. 1996). The engrafted cells were analyzed for expression of surface markers that define human hematopoietic cells. During the follow up period of up to 18 weeks, the high dose infused group had increased hUCB engraftment compared with the low dose infused group in peripheral blood (Fig 1A), bone marrow (Fig 1B & 1C) and spleen (Fig 1D), which is consistent with reported clinical observations that infused cell dosage is inversely correlated with time to engraftment (Migliaccio et al. 2000 Blood). Interestingly, we observed different lymphoid subset frequencies between low and high dose infused groups at the post-engraftment stage (18 weeks post transplantation) (data not shown). To investigate different lymphoid subset engraftment frequencies in low and high dose hUCB transplanted recipient mice at early engraftment stage, peripheral blood and hematopoietic organs were collected and analyzed up to 10 weeks post transplantation. The low dose infused group had significantly lower CD3+ (T cells) and CD56+ (NK cells) frequency in peripheral blood at 4 and 8 weeks (Fig 2A & 3A). More importantly, CD3+ (T cells) frequency was close to non-detectable in the bone marrow and spleen in the low dose infused group (Fig 2B & 2C), and CD56 (NK cells) frequency was decreased in the low dose infused group compared with the high dose infused group (Fig 3B & 3C). The absolute CD3+ and CD56+ number, displayed as fold difference, were even more dramatically decreased in the femur (Fig 2D & 3D) and the spleen (Fig 2E & 3E) of low dose infused group. Because of the substantial difference in T cell subset frequencies between the two dosage groups in bone marrow and spleen, thymuses were collected and analyzed to study T cell development and maturation. Engraftment of hCD45+ cells in the thymuses were observed in 10 out of 15 animals (66.7%) in the low dose infused group and 12 out of 14 animals (85.7%) in the high dose infused group. Interestingly, in animals with high hCD45+ frequency, the total thymocyte CD3+ frequency was lower in the low dose infused group (Fig 4A). Additionally, the low dose infused group had lower CD3+CD4+ T cell frequency (Fig 4B) and higher CD3+CD4+CD8+ T cell frequency (Fig 4C), suggesting low dose infused group had a decreased mature T cell population and increased immature T cell population in the thymus. In contrast, the low dose hUCB CD34+ cells infused group had increased hCD19 (B cells) frequency in the peripheral blood, bone marrow and spleen (Fig 5A-5C), while the absolute hCD19 (B cells), displayed as fold difference, did not show a statistically significant difference between the two groups (Fig 5D & 5E). Conclusions In summary, our findings suggest that (1) transplanted hUCB cell dosage is inversely correlated with time to engraftment (2) low transplanted hUCB cell dosage resulted in skewed immune cell population which may contribute to delayed immune recovery after allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

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Manjum, Marjanul, Saheed Adewale Lateef, Hunter Addison McRay, William Earl Mustain y Golareh Jalilvand. "Low-Cost Processing of Highly Durable (>1000 cycles) Sulfur Cathodes for Li-S Batteries". ECS Meeting Abstracts MA2022-02, n.º 6 (9 de octubre de 2022): 588. http://dx.doi.org/10.1149/ma2022-026588mtgabs.

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Lithium-sulfur (Li-S) batteries are one of the promising alternatives to modern Lithium-ion Battery (LIB) technology due to their superior specific energy density, which can satisfy the emerging needs of advanced energy storage applications such as electric vehicles and grid-scale energy storage and delivery. However, achieving this high specific energy density is hampered by several challenges inherent to the properties of sulfur and its discharge products. One major issue is related to the insulating nature of S and its fully discharged product (Li2S), which often leads to low utilization of the active material and poor rate capability. The poor electronic conductivity of these species can be overcome by utilizing conductive hosts, though they are dilutive and decrease the energy density, meaning that their mass ratio to the active material should be as low as possible [1]. Another crucial issue relates to the undesired solubility of certain sulfur discharge products, so-called long-chain Li polysulfides (LiPSs), in the conventional ether-based liquid electrolyte. The solubility of long-chain LiPSs promotes their free back-and-forth transport between the positive and negative electrodes, which results in poor cyclability and capacity decay [2, 3]. Despite the efforts to engineer and control the undesired LiPSs shuttling effect, advances have been mostly limited to a small number of cycles (100-200), or the need for complex and often expensive synthesis that has limited the rational development of new sulfur cathodes. At present, a large majority of the sulfur cathode research has focused on nano-architectured electrodes using 2D and 3D host materials for sulfur, such as carbon nanotubes, graphene, conductive scaffolds, yolk-shell structures, and the like, to increase the conductivity and alleviate the LiPSs shuttling [4]. Although these approaches have helped to increase the achievable capacity, and sometimes the cyclability, their synthesis methods have been highly complex, meaning that their manufacturing cost will be high. Also, in operating cells, it is highly unlikely that these complex structures can be effectively reproduced upon many charge-discharge cycles – meaning that capacity loss is essentially inevitable. Thus, developing novel, yet affordable and scalable, cathode architectures that can enhance the rapid transport of Li-ions to active sites for electrode reactions, accommodate discharge-induced volume expansion, and minimize the shuttling mechanism by sulfur encapsulation are still in great need. In this work, we present a low-cost and scalable processing method for highly durable sulfur cathodes containing commercial sulfur, carbon black, and polyvinylidene fluoride (PVDF). The sulfur cathode slurry was prepared through a simple and scalable recipe where the degree of binder dissolution into the solvent was controlled before electrode deposition. Variables such as the solvent:binder ratio, dissolution time, and agitation will be discussed. The microstructure of the sulfur cathodes was characterized using scanning electron microscopy. Through controlled dissolution of binder, a porous, swollen network of binder was achieved that adhered the sulfur and carbon particles while providing a highly porous structure that can accommodate the sulfur volume expansion during discharge and impede dissolution of the discharge products into the electrolyte by physically trapping them. The cycling performance of the sulfur cathodes prepared through the present novel processing was tested at C/10 and compared with those prepared through the conventional production techniques. The sulfur cathodes prepared with this novel electrode processing offered impressive capacity retention of 80% after 1000 cycles suggesting a considerable improvement in the shuttling effect and active material preservation. These results are expected to help move the production and manufacturing of Li-S batteries forward. References -J. Lee, T.-H. Kang, H.-Y. Lee, J. S. Samdani, Y. Jung, C. Zhang, Z. Yu, G.-L. Xu, L. Cheng, S. Byun et al., Advanced Energy Materials, vol. 10, no. 22, p. 1903934, 2020. Yang, G. Zheng, and Y. Cui, Chemical Society Reviews, vol. 42, no. 7, pp. 3018–3032, 2013. She, Y. Sun, Q. Zhang, and Y. Cui., Chemical society reviews, vol. 45, no. 20, pp. 5605-5634, 2016. Zhou, D. L. Danilov, R.-A. Eichel, and P. H. L. Notten, Advanced Energy Materials, vol. 1, p. 2001304, 2020.

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Han, Xiaoyu, Qimanguli Saiding, Xiaolu Cai, Yi Xiao, Peng Wang, Zhengwei Cai, Xuan Gong, Weiming Gong, Xingcai Zhang y Wenguo Cui. "Intelligent Vascularized 3D/4D/5D/6D-Printed Tissue Scaffolds". Nano-Micro Letters 15, n.º 1 (31 de octubre de 2023). http://dx.doi.org/10.1007/s40820-023-01187-2.

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AbstractBlood vessels are essential for nutrient and oxygen delivery and waste removal. Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering. Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer, mainly including but not limited to 3D printing, but also 4D printing, 5D printing and 6D printing. It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds. Herein, the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue. Additionally, the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories: functional vascularized 3D printed scaffolds, cell-based vascularized 3D printed scaffolds, vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds. Finally, a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering, cardiovascular system, skeletal muscle, soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

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Nazir, Safdar. "Insulator-to-half metal transition and enhancement of structural distortions in $$\text {Lu}_2 \text {NiIrO}_6$$ double perovskite oxide via hole-doping". Scientific Reports 11, n.º 1 (13 de enero de 2021). http://dx.doi.org/10.1038/s41598-020-80265-6.

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AbstractUsing density functional theory calculations, we found that recently high-pressure synthesized double perovskite oxide $$\text {Lu}_2 \text {NiIrO}_6$$ Lu 2 NiIrO 6 exhibits ferrimagnetic (FiM) Mott-insulating state having an energy band gap of 0.20 eV which confirms the experimental observations (Feng et al. in Inorg Chem 58:397–404, 2019). Strong antiferromagnetic superexchange interactions between high-energy half-filled $$\text {Ni}^{+2}$$ Ni + 2 -$$e_g^2\uparrow$$ e g 2 ↑ and low-energy partially filled $$\text {Ir}^{+4}\,t_{2g}^3\uparrow t_{2g}^2\downarrow$$ Ir + 4 t 2 g 3 ↑ t 2 g 2 ↓ orbitals, results in a FiM spin ordering. Besides, the effect of 3d transition metal (TM = Cr, Mn, and Fe) doping with 50% concentration at Ni sites on its electronic and magnetic properties is explored. It is established that smaller size cation-doping at the B site enhances the structural distortion, which further gives strength to the FiM ordering temperature. Interestingly, our results revealed that all TM-doped structures exhibit an electronic transition from Mott-insulating to a half-metallic state with effective integral spin moments. The admixture of Ir 5d orbitals in the spin-majority channel are mainly responsible for conductivity, while the spin minority channel remains an insulator. Surprisingly, a substantial reduction and enhancement of spin moment are found on non-equivalent Ir and oxygen ions, respectively. This leads the Ir ion in a mixed-valence state of $$+4$$ + 4 and $$+5$$ + 5 in all doped systems having configurations of $$5d^5$$ 5 d 5 ($$t_{2g}^3\uparrow t_{2g}^2\downarrow$$ t 2 g 3 ↑ t 2 g 2 ↓ ) and $$5d^4$$ 5 d 4 ($$t_{2g}^2\uparrow t_{2g}^2\downarrow$$ t 2 g 2 ↑ t 2 g 2 ↓ ), respectively. Hence, the present work proposes that doping engineering with suitable impurity elements could be an effective way to tailor the physical properties of the materials for their technological potential utilization in advanced spin devices.

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Di Berardino, C., L. Liverani, G. Capacchietti, A. Peserico, A. R. Boccaccini y B. Barboni. "P-440 Impact of electrospun scaffold topology on the performance of in-vitro Folliculogenesis applied to preantral ovine follicles". Human Reproduction 37, Supplement_1 (29 de junio de 2022). http://dx.doi.org/10.1093/humrep/deac107.415.

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Abstract Study question How to improve in-vitro Folliculogenesis (ivF) protocols to address the enlarged demand of fertility preservation? Summary answer Tissue engineering-based approach opens new frontiers for ivF improving 3D-technologies addressed to support immature-ovarian-follicle-growth to obtain an increased number of competent oocytes enrolled in Assisted-Reproductive-Technology. What is known already ivF is a promising Assisted-Reproductive-Technology (ART) for preserving and restoring fertility. This technology potentially reproduces the early stages of folliculogenesis and oogenesis in-vitro allowing to move a large amount of oocyte on individual basis towards the validated protocol of in-vitro maturation/in-vitro fertilization (IVM/IVF). The current availability of biocompatible-supporting materials offers the challenging opportunity to mimic the native organ stroma in order to better reproduce the 3D environmental conditions leading to synergic follicles-oocyte development in-vitro with the aim to improve the performance of ivF in translational large sized mammal models. Study design, size, duration The present research aimed to compare preantral (PA) follicles culture on two different typologies of scaffolds fabricated using PCL(poly(epsilon caprolactone)), respectively made with patterned and randomly aligned fibers (PCL-Patterned/PCL-Randomic) with a standardized-single-follicle scaffold-free-method (3D-oil), widely validated on ovine model (Cecconi et al., 2004). The culture outcomes are compared analyzing follicle/oocyte growth, percentage of antrum differentiation and the incidence of meiotic competence, by exposing ivF growing oocytes to IVM protocol. Participants/materials, setting, methods PA follicles (mean size diameter: 250±4μm), mechanically isolated from slaughterhoused lamb ovaries, were individually cultured on electrospun PCL scaffolds (patterned vs randomic) or using the 3D-oil method. ivF were cultured alphaMEM-Fetal Bovine Serum free medium (5% Knockout Serum Replacement) supplemented with 4 IU/mL of equine Chorionic Gonadotropin (Di Berardino et al., 2021). At the end of ivF (14-days) the fully-grown oocytes isolated from early-antral follicles were tested on IVM. Main results and the role of chance PCL-Patterned electrospun scaffolds were able to strongly support a synergic oocyte and follicular growth. The 3D culture on Patterned electrospun scaffold supported the highest viability of follicles (87.5% vs 63% under 3D-oil conditions). On the contrary, the highest incidence of degenerated follicles was observed in cultures performed using PCL-Randomic materials (55 vs 37% vs 12.5% for PCL-Randomic vs 3D-oil vs PCL-Patterned, respectively; p <0.0004). The greatest follicle diameter increment (74.7±1 vs 70±0.4 vs 60.9±2%, for PCL-Patterned vs 3D-oil vs PCL-Randomic, respectively p <0.0007) and rate of antrum differentiation (87.5% vs 45% and vs 63%, for PCL-Patterned vs 3D-oil vs PCL-Randomic, for both p <0.0001) were observed in PA ovine follicles cultured on PCL-Patterned scaffolds. Furthermore, PCL-Patterned electrospun scaffolds supported a complete functional development of the oocyte compartment. More in detail, the majority of fully grown oocytes isolated from early- antral follicles grown on PCL-Patterned materials reached the metaphase-II stage (MII 80%) at the end of IVM in comparison to the significant lower percentage in 3D-oil (MII 68%, p =0.04) and PCL-Randomic (MII 18%, p <0.0001) protocols, respectively. Limitations, reasons for caution - Wider implications of the findings Tissue engineering scaffold-based approach represents a valid strategy generating a multi-organ in-vitro system, where different compartments may cooperate generating the complexity of paracrine-mechanism controlling early-follicles outcomes. Scaffold topology is essential to control early-follicles development. Indeed, exclusively PCL-Patterned can preserve long-term follicle 3D-microarchitecture supporting in-vitro oogenesis up to a complete meiotic-competence-acquisition. Trial registration number not applicable

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Di Nisio, V., K. Papaikonomou, Z. Xiao, A. Damdimopoulos, P. Damdimopoulou y A. Salumets. "P-425 Biosilk and ovarioids: recombinant silk as a new tool for establishing a 3D-culture system for human ovarian primary cells". Human Reproduction 38, Supplement_1 (1 de junio de 2023). http://dx.doi.org/10.1093/humrep/dead093.775.

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Abstract Study question Can Biosilk be used as scaffold for establishing a 3D-culture system to support attachment and growth of primary cells derived from adult ovarian biopsies? Summary answer The use of recombinant spider silk-based scaffold allowed the formation of 3D-structured ovarioids from both cortex and medulla isolated from 5 different patients. What is known already Fertility in women is adversely affected by several factors, such as age, environmental pollutants and diseases requiring gonadotoxic treatments. Understanding ovarian cell composition and organization may pave the way to novel fertility preservation methods with the ultimate goal of being applied to clinics. So far, there are no clinically established methods for in vitro growth and maturation of human ovarian follicles leading to mature competent oocytes. Therefore, exploring new 3D-culture systems for in vitro reconstruction of ovarian somatic cell niche could lead to development of novel tools to support growth of patient-specific follicles. Study design, size, duration Ovarian tissue was collected from gender reassignment patients (GRP) after informed written consent at Karolinska University Hospital Huddinge from 2019 to 2022. After separation of cortex and medulla, the samples were mechanically and enzymatically dissociated into single-cell suspensions and used to evaluate 3D- and 2D-culture methods. Freshly fixed biopsies from cortex and medulla (3x3x1 mm3) were used as control for the transcriptomic analysis and RNA-FISH assay. Participants/materials, setting, methods Tissue was obtained from five patients aged 23-31 years. Dissociated primary somatic cells seeded on Biosilk-foam scaffolds were kept in culture for 2 weeks, followed by detachment, equal division of the foams and suspension culture for additional 4 weeks (BioSilk-Ovarioids, BSO). BSOs were harvested in PFA and RNAlater (n = 6/patient, respectively) for morphological and transcriptomic analysis. Protein ZO1, and cell type-specific marker genes (AMHR2, PDGFRa, CLDN5, GJA4) were evaluated via immunodetection and RNA-FISH assay, respectively. Main results and the role of chance The sizes of BSOs from both cortex and medulla ranged between 0.5-1 mm at the end of the culture, appearing highly compacted under optical microscope. HE-stained BSO sections revealed that cells were distributed throughout the foams, showing good attachment and distribution. Marker genes were selected for specific cell types [AMHR2-granulosa, PDGFRa-stroma, CLDN5-endothelial, GJA4-perivascular cells (Wagner et al. 2020)] and used to study the representation of different somatic cells in the BSOs. The RNA-FISH analysis confirmed the presence of all cell type-specific marker genes, with predominating presence of stromal cells (PDGFRa). Newly formed ZO1-specific gap junctions were detected in both cortex- and medulla-derived BSOs, appearing mainly in the outer part of the structures. Interestingly, cell layers surrounding the original Biosilk scaffold were observed, especially in medulla-BSOs. Transcriptomic profiling of the samples showed clear separation to three main clusters by principal component analysis: freshly fixed tissue, 2D-cultures, and BSO. Moreover, clustering analysis of differentially expressed genes (DEGs) showed the presence of gene clusters in fresh tissues affected by both 3D/2D-cultures. Further analyses will focus on identification of significantly affected gene ontologies and pathways, which will further guide the optimization of the BSO culture system. Limitations, reasons for caution The tissue was derived from GRPs who always receive androgen treatments prior to surgery. As hormonal treatment may affect the ovarian environment, further trials with untreated patient samples will be needed to generalize the model to fertility preservation patients. Wider implications of the findings The establishment and development of the BSO 3D-culture system may enable the construction of patient-specific clinically significant tools for in vitro folliculogenesis. This would open new avenues for fertility restoration in patients who cannot receive auto-transplants and treatment of infertility in premature ovarian insufficiency if residual follicles remain in tissue. Trial registration number Not applicable

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