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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/29448967/facial-nerve-stimulation-in-normal-pigs-and-healthy-human-volunteers-transitional-development-of-a-medical-device-for-the-emergency-treatment-of-ischemic-stroke
#1
Olivia Sanchez, Andrea García, Fernando Castro-Prado, Miriam Perez, Rafael Lara-Estrada, Martin Ramirez-Meza, Montserrat Godinez, Michael L Coco, Joaquín Azpiroz, Mark K Borsody, Emilio Sacristán
BACKGROUND: Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29448963/academic-medical-centers-as-innovation-ecosystems-to-address-population-omics-challenges-in-precision-medicine
#2
REVIEW
Patrick J Silva, Valerie M Schaibley, Kenneth S Ramos
While the promise of the Human Genome Project provided significant insights into the structure of the human genome, the complexities of disease at the individual level have made it difficult to utilize -omic information in clinical decision making. Some of the existing constraints have been minimized by technological advancements that have reduced the cost of sequencing to a rate far in excess of Moore's Law (a halving in cost per unit output every 18 months). The reduction in sequencing costs has made it economically feasible to create large data commons capturing the diversity of disease across populations...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29448962/non-viral-gene-delivery-systems-for-tissue-repair-and-regeneration
#3
REVIEW
Pan Wu, Haojiao Chen, Ronghua Jin, Tingting Weng, Jon Kee Ho, Chuangang You, Liping Zhang, Xingang Wang, Chunmao Han
Critical tissue defects frequently result from trauma, burns, chronic wounds and/or surgery. The ideal treatment for such tissue loss is autografting, but donor sites are often limited. Tissue engineering (TE) is an inspiring alternative for tissue repair and regeneration (TRR). One of the current state-of-the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS) have great potential for TE and have several advantages over viral delivery including lower immunogenicity and toxicity, better cell specificity, better modifiability, and higher productivity...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29448960/double-negative-cd27-igd-b-cells-are-expanded-in-nsclc-and-inversely-correlate-with-affinity-matured-b-cell-populations
#4
Sara M Centuori, Cecil J Gomes, Samuel S Kim, Charles W Putnam, Brandon T Larsen, Linda L Garland, David W Mount, Jesse D Martinez
BACKGROUND: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A + CD27 - IgD - ...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29448956/immunomodulatory-plasticity-of-mesenchymal-stem-cells-a-potential-key-to-successful-solid-organ-transplantation
#5
REVIEW
Urvashi Kaundal, Upma Bagai, Aruna Rakha
Organ transplantation remains to be a treatment of choice for patients suffering from irreversible organ failure. Immunosuppressive (IS) drugs employed to maintain the allograft have shown excellent short-term graft survival, but, their long-term use could contribute to immunological and non-immunological risk factors, resulting in graft dysfunctionalities. Upcoming IS regimes have highlighted the use of cell-based therapies, which can eliminate the risk of drug-borne toxicities while maintaining efficacy of the treatment...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29422056/turning-the-tables-on-cytomegalovirus-targeting-viral-fc-receptors-by-cars-containing-mutated-ch2-ch3-igg-spacer-domains
#6
Julia Proff, Charlotte U Brey, Armin Ensser, Wolfgang Holter, Manfred Lehner
BACKGROUND: During infection with human cytomegalovirus (HCMV) several viral proteins occur on cell surfaces in high quantity. We thus pursue an HLA-independent approach for immunotherapy of HCMV using chimeric antigen receptors (CARs) and bispecific BiTE® antibody constructs. In this context, HCMV-encoded proteins that mediate viral immune evasion and bind human IgG might represent particularly attractive target antigens. Unlike in observations of similar approaches for HIV and hepatitis B and C viruses, however, HCMV-infected cells develop a striking resistance to cytotoxic effector functions at later stages of the replication cycle...
February 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29415739/hepcidin-an-emerging-and-important-player-in-brain-iron-homeostasis
#7
REVIEW
Driton Vela
Hepcidin is emerging as a new important factor in brain iron homeostasis. Studies suggest that there are two sources of hepcidin in the brain; one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain. The most important source of hepcidin in the brain are glial cells. Role of hepcidin in brain functions has been observed during neuronal iron-load and brain hemorrhage, where secretion of abundant hepcidin is related with the severity of brain damage...
February 7, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29409514/immune-monitoring-and-tcr-sequencing-of-cd4-t-cells-in-a-long-term-responsive-patient-with-metastasized-pancreatic-ductal-carcinoma-treated-with-individualized-neoepitope-derived-multipeptide-vaccines-a-case-report
#8
Katja Sonntag, Hisayoshi Hashimoto, Matthias Eyrich, Moritz Menzel, Max Schubach, Dennis Döcker, Florian Battke, Carolina Courage, Helmut Lambertz, Rupert Handgretinger, Saskia Biskup, Karin Schilbach
BACKGROUND: Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. METHODS: Vaccination started during chemotherapy in second complete remission and continued monthly thereafter...
February 6, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29409505/open-label-pilot-for-treatment-targeting-gut-dysbiosis-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-neuropsychological-symptoms-and-sex-comparisons
#9
Amy Wallis, Michelle Ball, Henry Butt, Donald P Lewis, Sandra McKechnie, Phillip Paull, Amber Jaa-Kwee, Dorothy Bruck
BACKGROUND: Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS. METHODS: An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons...
February 6, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29402328/expression-of-the-hippo-transducer-taz-in-association-with-wnt-pathway-mutations-impacts-survival-outcomes-in-advanced-gastric-cancer-patients-treated-with-first-line-chemotherapy
#10
Elisa Melucci, Beatrice Casini, Livia Ronchetti, Laura Pizzuti, Francesca Sperati, Matteo Pallocca, Francesca De Nicola, Frauke Goeman, Enzo Gallo, Carla Azzurra Amoreo, Domenico Sergi, Irene Terrenato, Patrizia Vici, Luigi Di Lauro, Maria Grazia Diodoro, Edoardo Pescarmona, Maddalena Barba, Marco Mazzotta, Marcella Mottolese, Maurizio Fanciulli, Gennaro Ciliberto, Ruggero De Maria, Simonetta Buglioni, Marcello Maugeri-Saccà
BACKGROUND: An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. METHODS: In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice...
February 5, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29391028/improvement-of-severe-myalgic-encephalomyelitis-chronic-fatigue-syndrome-symptoms-following-surgical-treatment-of-cervical-spinal-stenosis
#11
Peter C Rowe, Colleen L Marden, Scott Heinlein, Charles C Edwards
BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a potentially disabling disorder. Little is known about the contributors to severe forms of the illness. We describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis. METHODS: All patients satisfied clinical criteria for ME/CFS and orthostatic intolerance, and were later found to have cervical spinal stenosis...
February 2, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29382345/investigation-of-genetic-variation-and-lifestyle-determinants-in-vitamin-d-levels-in-arab-individuals
#12
Massimo Mezzavilla, Sara Tomei, Fadi Alkayal, Motasem Melhem, Maisa M Ali, Monira Al-Arouj, Abdullah Bennakhi, Osama Alsmadi, Naser Elkum
BACKGROUND: Differences in the concentrations of circulating 25-hydroxyvitamin D [25(OH)D] are associated with a wide range of health outcomes; however, most studies on genetic variants that impact 25(OH)D levels have been conducted in European populations. Here we aimed to identify common genetic variants that affect vitamin D concentrations in individuals of self-reported Arab ethnicity. METHODS: The study included 1151 Arab subjects living in Kuwait. Common variants of single-nucleotide polymorphisms and genes previously associated with vitamin D levels, such as GC, PDE3B, CYP2R1, and NADSYN1, were genotyped...
January 30, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29378619/chromosome-conformation-signatures-define-predictive-markers-of-inadequate-response-to-methotrexate-in-early-rheumatoid-arthritis
#13
Claudio Carini, Ewan Hunter, Aroul S Ramadass, Jayne Green, Alexandre Akoulitchev, Iain B McInnes, Carl S Goodyear
BACKGROUND: There is a pressing need in rheumatoid arthritis (RA) to identify patients who will not respond to first-line disease-modifying anti-rheumatic drugs (DMARD). We explored whether differences in genomic architecture represented by a chromosome conformation signature (CCS) in blood taken from early RA patients before methotrexate (MTX) treatment could assist in identifying non-response to DMARD and, whether there is an association between such a signature and RA specific expression quantitative trait loci (eQTL)...
January 29, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29378596/myeloid-derived-suppressor-cells-in-transplantation-the-dawn-of-cell-therapy
#14
REVIEW
Weitao Zhang, Jiawei Li, Guisheng Qi, Guowei Tu, Cheng Yang, Ming Xu
Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation...
January 29, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29370861/toolbox-for-research-or-how-to-facilitate-a-central-data-management-in-small-scale-research-projects
#15
Martin Bialke, Henriette Rau, Oliver C Thamm, Ronny Schuldt, Peter Penndorf, Arne Blumentritt, Robert Gött, Jens Piegsa, Thomas Bahls, Wolfgang Hoffmann
BACKGROUND: In most research projects budget, staff and IT infrastructures are limiting resources. Especially for small-scale registries and cohort studies professional IT support and commercial electronic data capture systems are too expensive. Consequently, these projects use simple local approaches (e.g. Excel) for data capture instead of a central data management including web-based data capture and proper research databases. This leads to manual processes to merge, analyze and, if possible, pseudonymize research data of different study sites...
January 25, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29370858/chronic-diseases-inflammation-and-spices-how-are-they-linked
#16
REVIEW
Ajaikumar B Kunnumakkara, Bethsebie L Sailo, Kishore Banik, Choudhary Harsha, Sahdeo Prasad, Subash Chandra Gupta, Alok Chandra Bharti, Bharat B Aggarwal
Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc...
January 25, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29370817/establishment-and-genomic-characterizations-of-patient-derived-esophageal-squamous-cell-carcinoma-xenograft-models-using-biopsies-for-treatment-optimization
#17
Jianling Zou, Ying Liu, Jingyuan Wang, Zhentao Liu, Zhihao Lu, Zuhua Chen, Zhongwu Li, Bin Dong, Wenwen Huang, Yanyan Li, Jing Gao, Lin Shen
BACKGROUND: Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application. METHODS: Fresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice...
January 25, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29370807/voltammetric-analysis-for-fast-and-inexpensive-diagnosis-of-urinary-tract-infection-a-diagnostic-study
#18
Diana Lelli, Claudio Pedone, Pamela Alemanno, Alessandra Bertini, Claudia Di Gioia, Sara Fazzina, Giorgio Pennazza, Marco Santonico, Simone Grasso, Alessandro Zompanti, Silvia Angeletti, Raffaele Antonelli Incalzi
BACKGROUND: Dipstick test is widely used to support the diagnosis of urinary tract infections (UTI). It is effective in ruling out UTI, but urine culture is needed for diagnosis confirmation. In this study we compared the accuracy of voltammetric analysis (VA) with that of DT to detect UTI (diagnosed using urine culture), and its usefulness as a second-stage test in people with positive DT. METHODS: 142 patients were enrolled with no exclusion criteria. VA was performed using the BIONOTE device...
January 25, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29368612/enhanced-clinical-scale-manufacturing-of-tcr-transduced-t-cells-using-closed-culture-system-modules
#19
Jianjian Jin, Nikolaos Gkitsas, Vicki S Fellowes, Jiaqiang Ren, Steven A Feldman, Christian S Hinrichs, David F Stroncek, Steven L Highfill
BACKGROUND: Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. METHODS: TCRs that target human papillomavirus E6 and E7 were independently tested...
January 24, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29361946/the-prognostic-value-of-preoperative-prognostic-nutritional-index-in-patients-with-hypopharyngeal-squamous-cell-carcinoma-a-retrospective-study
#20
Lu-Lu Ye, Ronald Wihal Oei, Fang-Fang Kong, Cheng-Run Du, Rui-Ping Zhai, Qing-Hai Ji, Chao-Su Hu, Hong-Mei Ying
BACKGROUND: To analyze the prognostic value of preoperative prognostic nutritional index (PNI) in predicting the survival outcome of hypopharyngeal squamous cell carcinoma (HPSCC) patients receiving radical surgery. METHODS: From March 2006 to August 2016, 123 eligible HPSCC patients were reviewed. The preoperative PNI was calculated as serum albumin (g/dL) × 10 + total lymphocyte count (mm-3) × 0.005. These biomarkers were measured within 2 weeks prior to surgery...
January 24, 2018: Journal of Translational Medicine
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