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Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Sandesh Parajuli, Didier A Mandelbrot, Brenda Muth, Maha Mohamed, Neetika Garg, Fahad Aziz, Robert R Redfield, Weixiong Zhong, Brad C Astor, Arjang Djamali
Background: There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation. Methods: In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks...
December 2017: Transplantation Direct
Daniel Walsh, Katherine Glass, Samantha Morris, Horace Zhang, Isabel McRae, Noel Anderson, Alysha Alfieri, Sara Perl Egendorf, Shana Holberton, Shahandeh Owrang, Zhongqi Cheng
Urban soil is an ongoing source for lead (Pb) and other pollutant exposure. Sources of clean soil that are locally-available, abundant and inexpensive are needed to place a protective cover layer over degraded urban soil to eliminate direct and indirect pollutant exposures. This study evaluates a novel sediment exchange program recently established in New York City (NYC Clean Soil Bank, CSB) and found that direct exchange of surplus sediment extracted from urban construction projects satisfies these criteria...
March 10, 2018: Journal of Environmental Management
Matthias Vonbrüll, Elisabeth Riegel, Christian Halter, Michaela Aigner, Holger Bock, Birgit Werner, Thomas Lindhorst, Thomas Czerny
There have been many attempts to unveil the therapeutic potential of antisense molecules during the last decade. Due to its specific role in canonical Wnt signalling, β-catenin is a potential target for an antisense-based antitumour therapy. In order to establish such a strategy with peptide nucleic acids, we developed a reporter assay for quantification of antisense effects. The luciferase-based assay detects splice blocking with high sensitivity. Using this assay, we show that the splice donor of exon 13 of β-catenin is particularly suitable for an antisense strategy, as it results in a truncated protein which lacks transactivating functions...
March 9, 2018: Molecular Biotechnology
Timothy J Petros
The mammalian brain develops from a simple sheet of neuroepithelial cells into an incredibly complex structure containing billions of neurons with trillions of synapses. Understanding how intrinsic genetic programs interact with environmental cues to generate neuronal diversity and proper connectivity is one of the most daunting challenges in developmental biology. We recently explored this issue in forebrain GABAergic inhibitory interneurons, an extremely diverse population of neurons that are classified into distinct subtypes based on morphology, neurochemical markers, and electrophysiological properties...
2018: Journal of Experimental Neuroscience
Emil Andersen, Lars Roed Ingerslev, Odile Fabre, Ida Donkin, Ali Altıntaş, Soetkin Versteyhe, Thue Bisgaard, Viggo B Kristiansen, David Simar, Romain Barrès
BACKGROUND: Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function of preadipocytes. METHODS: The transcriptomic profile of visceral adipose tissue preadipocytes collected from Lean, Obese and Obese with T2D was assessed throughout in vitro differentiation using RNA sequencing...
February 20, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Takahiro Kamiya, Desmond Wong, Yi Tian Png, Dario Campana
Practical methods are needed to increase the applicability and efficacy of chimeric antigen receptor (CAR) T-cell therapies. Using donor-derived CAR-T cells is attractive, but expression of endogenous T-cell receptors (TCRs) carries the risk for graft-versus-host-disease (GVHD). To remove surface TCRαβ, we combined an antibody-derived single-chain variable fragment specific for CD3ε with 21 different amino acid sequences predicted to retain it intracellularly. After transduction in T cells, several of these protein expression blockers (PEBLs) colocalized intracellularly with CD3ε, blocking surface CD3 and TCRαβ expression...
March 13, 2018: Blood Advances
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
Jonathan Canaani, Myriam Labopin, Xiao-Jun Huang, William Arcese, Fabio Ciceri, Didier Blaise, Giuseppe Irrera, Lucia Lopez Corral, Benedetto Bruno, Stella Santarone, Maria Teresa Van Lint, Antonin Vitek, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation...
March 2, 2018: American Journal of Hematology
Eva Marxen, Liang Jin, Jette Jacobsen, Christian Janfelt, Birgitte Hyrup, Joseph A Nicolazzo
PURPOSE: The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS: The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [3 H]-nicotine and [14 C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers...
February 21, 2018: Pharmaceutical Research
Xiaolei Lin, Yue Wu, Yana Fu, Qi Dai
RATIONALE: To report a case of late spontaneous reattachment of Descemet membrane (DM) detachment after deep anterior lamellar keratoplasty (DALK). PATIENT CONCERNS: A 50-year-old woman with stromal corneal scarring underwent a DALK with the big bubble technique. The DM detachment and double anterior chamber were observed on the first day after operation. DIAGNOSES: Descemet membrane detachment after deep anterior lamellar keratoplasty [Oculus Dexter (OD), indicates right eye]...
February 2018: Medicine (Baltimore)
Yohei Yamada, Ken Hoshino, Yasushi Fuchimoto, Kentaro Matsubara, Taizo Hibi, Hiroshi Yagi, Yuta Abe, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Takahito Yagi, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto, Tatsuya Suzuki, Keiichi Kubota, Tomoharu Yoshizumi, Yoshihiko Maehara, Yukihiro Inomata, Yuko Kitagawa, Hiroto Egawa, Tatsuo Kuroda
Background: Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx...
February 2018: Transplantation Direct
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
Fei Li, Myles H Alderman, Aya Tal, Ramanaiah Mamillapalli, Alexis Coolidge, Demetra Hufnagel, Zhihao Wang, Elham Neisani, Stephanie Gidicsin, Graciela Krikun, Hugh S Taylor
Endometriosis is ectopic growth of endometrial tissue traditionally thought to arise through retrograde menstruation. We aimed to determine if cells derived from endometriosis could enter vascular circulation and lead to hematogenous dissemination. Experimental endometriosis was established by transplanting endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice. Using flow cytometry, we identified DsRed+ cells in blood of animals with endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem cell (MSC) biomarkers, but not hematopoietic stem cell markers...
February 16, 2018: Stem Cells
Kriti M Jain, Prashanth Bhat, Cathy Maulsby, Alexandria Andersen, Tomas Soto, Ashley Tarrant, David R Holtgrave, Erin Nortrup, Melissa Werner, Laurie Dill
Purpose Using a mixed-methods formative evaluation, the purpose of this study was to provide a broad overview of the Alabama eHealth programme set-up and initial patient outcomes. The Alabama eHealth programme uses telemedicine to provide medical care to people living with HIV in rural Alabama. It was led by a community-based organisation, Medical Advocacy and Outreach (MAO), and supported by AIDS United and the Corporation for National Community Service's Social Innovation Fund with matching support from non-federal donors...
January 1, 2018: Journal of Telemedicine and Telecare
Gerrit H J Kema, Amir Mirzadi Gohari, Lamia Aouini, Hesham A Y Gibriel, Sarah B Ware, Frank van den Bosch, Robbie Manning-Smith, Vasthi Alonso-Chavez, Joe Helps, Sarrah Ben M'Barek, Rahim Mehrabi, Caucasella Diaz-Trujillo, Elham Zamani, Henk J Schouten, Theo A J van der Lee, Cees Waalwijk, Maarten A de Waard, Pierre J G M de Wit, Els C P Verstappen, Bart P H J Thomma, Harold J G Meijer, Michael F Seidl
Host resistance and fungicide treatments are cornerstones of plant-disease control. Here, we show that these treatments allow sex and modulate parenthood in the fungal wheat pathogen Zymoseptoria tritici. We demonstrate that the Z. tritici-wheat interaction complies with the gene-for-gene model by identifying the effector AvrStb6, which is recognized by the wheat resistance protein Stb6. Recognition triggers host resistance, thus implying removal of avirulent strains from pathogen populations. However, Z. tritici crosses on wheat show that sex occurs even with an avirulent parent, and avirulence alleles are thereby retained in subsequent populations...
February 12, 2018: Nature Genetics
Kui Li, Wei-De Zhang
Conjugated polymers with tailored donor-acceptor units have recently attracted considerable attention in organic photovoltaic devices due to the controlled optical bandgap and retained favorable separation of charge carriers. Inspired by these advantages, an effective strategy is presented to solve the main obstructions of graphitic carbon nitride (g-C3 N4 ) photocatalyst for solar energy conversion, that is, inefficient visible light response and insufficient separation of photogenerated electrons and holes...
February 12, 2018: Small
Sarah M Clark, Chloe N Vaughn, Jennifer A Soroka, Xin Li, Leonardo H Tonelli
Accumulating evidence has shown that lymphocytes modulate behavior and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune deficient mice restores a number of neurobehavioral deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behavior during development remains unknown...
February 11, 2018: European Journal of Neuroscience
Himansu Sekhar Nanda, Ankur Harish Shah, Gautama Wicaksono, Oleksandr Pokholenko, Feng Gao, Ivan Djordjevic, Terry W J Steele
Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto poly (amidoamine) (PAMAM-G5) dendrimers. Herein, the structure activity relationships of platelet adhesion and activation is evaluated for the first time on the cured PAMAM-g-diazirine bioadhesives. Three strategies were employed to prevent healthy human donor platelets from adhering and activating on light cured bioadhesive surfaces: 1) Attenuation of cationic surface charge, 2) anti-fouling composites by incorporating heparin and alginate in uncured formulation, and 3) heparin wash of cured bioadhesive surface...
February 9, 2018: Biomacromolecules
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