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https://www.readbyqxmd.com/read/28820959/takinib-a-selective-tak1-inhibitor-broadens-the-therapeutic-efficacy-of-tnf-%C3%AE-inhibition-for-cancer-and-autoimmune-disease
#1
Juliane Totzke, Deepak Gurbani, Rene Raphemot, Philip F Hughes, Khaldon Bodoor, David A Carlson, David R Loiselle, Asim K Bera, Liesl S Eibschutz, Marisha M Perkins, Amber L Eubanks, Phillip L Campbell, David A Fox, Kenneth D Westover, Timothy A J Haystead, Emily R Derbyshire
Tumor necrosis factor alpha (TNF-α) has both positive and negative roles in human disease. In certain cancers, TNF-α is infused locally to promote tumor regression, but dose-limiting inflammatory effects limit broader utility. In autoimmune disease, anti-TNF-α antibodies control inflammation in most patients, but these benefits are offset during chronic treatment. TAK1 acts as a key mediator between survival and cell death in TNF-α-mediated signaling. Here, we describe Takinib, a potent and selective TAK1 inhibitor that induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer...
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28820942/the-effects-of-preheating-and-storage-temperature-on-aroma-profile-and-physical-properties-of-citrus-oil-emulsions
#2
Ying Yang, Chengying Zhao, Guifang Tian, Chang Lu, Shaojie Zhao, Yuming Bao, David Julian McClements, Hang Xiao, Jinkai Zheng
Citrus oils are used as good carrier oil for emulsion fabrication due to their special flavor and various health-promoting functions. In this study, the effects of preheating temperature (30, 40, 50, 60, and 70 oC) and storage temperature (4, 25 and 37 oC) on aroma profiles and physical properties of three citrus-oil (i.e. mandarin, sweet orange and bergamot oils) emulsions were systematically investigated for the first time. The results demonstrated the significant impact of temperature on aroma profile and physical properties...
August 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28820351/genomic-and-chromatin-features-shaping-meiotic-double-strand-break-formation-and-repair-in-mice
#3
Shintaro Yamada, Seoyoung Kim, Sam E Tischfield, Maria Jasin, Julian Lange, Scott Keeney
The SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated formation and action of both PRDM9-dependent histone modifications...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819111/community-outbreaks-of-group-a-streptococcus-revealed-by-genome-sequencing
#4
Claire E Turner, Luke Bedford, Nicholas M Brown, Kim Judge, M Estée Török, Julian Parkhill, Sharon J Peacock
The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819001/epigenomics-and-human-adaptation-to-high-altitude
#5
Colleen Glyde Julian
Over the past decade, major technological and analytical advancements have propelled efforts towards identifying the molecular mechanisms that govern human adaptation to high altitude. Despite remarkable progress with respect to the identification of adaptive genomic signals that are strongly associated with the 'hypoxia-tolerant' physiological characteristics of high-altitude populations, many questions regarding the fundamental biological processes underlying human adaptation remain unanswered. Vital to address these enduring questions will be to determine the role of epigenetic processes, or non-sequence based features of the genome, that are not only critical for the regulation of transcriptional responses to hypoxia but heritable across generations...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#6
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28818217/thirty-sixth-month-follow-up-of-first-in-human-use-of-cyanoacrylate-adhesive-for-treatment-of-saphenous-vein-incompetence
#7
Jose I Almeida, Julian J Javier, Edward G Mackay, Claudia Bautista, Daniel J Cher, Thomas M Proebstle
OBJECTIVE: The objective of this study was to evaluate the long-term safety and effectiveness of endovenous cyanoacrylate (CA)-based closure of incompetent great saphenous veins. METHODS: This was a prospective, single-arm, single-center feasibility study conducted at the Canela Clinic (La Romana, Dominican Republic) to assess the effectiveness and safety of a CA-based adhesive for great saphenous vein closure at 36 months after treatment. Thirty-eight subjects were treated by injection of small boluses of CA under ultrasound guidance and without the use of perivenous tumescent anesthesia or postprocedure graduated compression stockings...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28818062/ocular-toxicity-due-to-trametinib-and-dabrafenib
#8
Stephanie Sarny, Michael Neumayer, Julian Kofler, Yosuf El-Shabrawi
BACKGROUND: To report a case of uveitis and neuroretinal detachment in a patient treated with Trametinib and Dabrafenib due to metastatic cutaneous melanoma stage IV. CASE PRESENTATION: We evaluated slit lamp examination, fundoscopy, optical coherence tomography, fluorescein and indocyanine green angiography in a 66 years old man suffering visual loss. Fundoscopy showed serous neuroretinal detachment of the fovea accompanied with white spots surrounding the fovea in both eyes...
August 17, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28818056/adaptation-of-chinese-and-english-versions-of-the-ankylosing-spondylitis-quality-of-life-asqol-scale-for-use-in-singapore
#9
Ying Ying Leung, Weixian Lee, Nai Lee Lui, Matthew Rouse, Stephen P McKenna, Julian Thumboo
BACKGROUND: To cross-culturally adapt and validate the Singapore Chinese and Singapore English versions of the Ankylosing Spondylitis Quality of Life (ASQoL) scales. METHODS: Translation of the ASQoL into Singapore Chinese and English was performed by professional and lay translation panels. Field-testing for face and content validity was performed by interviewing ten Chinese speaking and ten English speaking axial spondyloarthritis (AxSpA) patients. AxSpA patients (either Chinese or English speaking) were invited to take part in validation surveys...
August 17, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28817460/high-demand-for-psychotherapy-in-patients-with-inflammatory-bowel-disease
#10
Thomas Klag, Nazar Mazurak, Laura Fantasia, Juliane Schwille-Kiuntke, Andreas Kirschniak, Claudius Falch, Martin Goetz, Nisar P Malek, Paul Enck, Jan Wehkamp
BACKGROUND: The relative contribution of psychological factors to the onset and course of inflammatory bowel diseases (IBD) is a matter of constant debate since its beginning, as is the clinical need and the efficacy of psychotherapeutic interventions. However, the perspective of patients with IBD has largely been ignored in this debate. METHODS: Psychometric tests including the Short-Form IBD Questionnaire (SIBDQ), the ADAP test measuring demand for psychotherapy, and the Fear-of-Progression Questionnaire Short Form as well as disease-related questions were positioned on the internet between December 2014 and January 2016...
August 16, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28817080/feasibility-study-of-an-optical-caustic-plasmonic-light-scattering-sensor-for-human-serum-anti-dengue-protein-e-antibody-detection
#11
Antonio A García, Lina S Franco, Miguel A Pirez-Gomez, José L Pech-Pacheco, Jorge F Mendez-Galvan, Carlos Machain-Williams, Lourdes Talavera-Aguilar, José H Espinosa-Carrillo, Miriam M Duarte-Villaseñor, Christian Be-Ortiz, Luz E Espinosa-de Los Monteros, Ariel Castillo-Pacheco, Julian E Garcina-Rejon
Antibody detection and accurate diagnosis of tropical diseases is essential to help prevent the spread of disease. However, most detection methods lack cost-effectiveness and field portability, which are essential features for achieving diagnosis in a timely manner. To address this, 3D-printed oblate spheroid sample chambers were fabricated to measure green light scattering of gold nanoparticles using an optical caustic focus to detect antibodies. Scattering signals of 20-200 nm gold nanoparticles using a green laser were compared to green light emitting diode (LED) light source signals and to Mie theory...
August 17, 2017: Diagnostics
https://www.readbyqxmd.com/read/28816621/use-disuse-paradigms-are-ubiquitous-concepts-in-characterizing-the-process-of-inheritance
#12
Sophie Juliane Veigl
In recent years, a Lamarckian theme has found its way back into academic discourse on evolution and inheritance. Especially the emerging field of transgenerational small RNAs has provided at least a proof of concept for the inheritance of acquired traits. Yet it remains unclear whether the Lamarckian concept of inheritance will in fact have its rennaisance or whether it will remain the rallying cry for the outlaws, heretics and enfants terribles of molecular biology. As unclear as the future of Lamarckian theory is its content and reference...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28816169/long-term-results-of-a-randomized-trial-comparing-iridium-implant-plus-external-beam-radiation-therapy-with-external-beam-radiation-therapy-alone-in-node-negative-locally-advanced-cancer-of-the-prostate
#13
Ian S Dayes, Sameer Parpia, Jaclyn Gilbert, Jim A Julian, Ian R Davis, Mark N Levine, Jinka Sathya
PURPOSE: To determine the impact on long-term survival from the addition of brachytherapy to external beam radiation therapy (EBRT) in patients with prostate cancer. METHODS AND MATERIALS: Between 1992 and 1997, 104 men with cT2-3, surgically staged node-negative prostate cancer were randomized to receive either EBRT (40 Gy/20 fractions) with iridium implant (35 Gy/48 hours) or EBRT alone (66 Gy/33 fractions) to the prostate. According to T stage, Gleason score, and prostate-specific antigen level, 60% of patients had high-risk disease...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28816143/radiation-therapy-versus-no-radiation-therapy-to-the-neo-breast-following-skin-sparing-mastectomy-and-immediate-autologous-free-flap-reconstruction-for-breast-cancer-patient-reported-and-surgical-outcomes-at-1-year-a-mastectomy-reconstruction-outcomes-consortium
#14
Andrew L Cooke, Julian Diaz-Abele, Tom Hayakawa, Ed Buchel, Kimberly Dalke, Pascal Lambert
PURPOSE: To determine whether adjuvant radiation therapy (RT) is associated with adverse patient-reported outcomes and surgical complications 1 year after skin-sparing mastectomy and immediate autologous free flap reconstruction for breast cancer. METHODS AND MATERIALS: We compared 24 domains of patient-reported outcome measures 1 year after autologous reconstruction between patients who received adjuvant RT and those who did not. A total of 125 patients who underwent surgery between 2012 and 2015 at our institution were included from the Mastectomy Reconstruction Outcomes Consortium study database...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28816091/mobile-three-dimensional-visualisation-technologies-for-clinician-led-fall-prevention-assessments
#15
Julian Hamm, Arthur G Money, Anita Atwal, Gheorghita Ghinea
The assistive equipment provision process is routinely carried out with patients to mitigate fall risk factors via the fitment of assistive equipment within the home. However, currently, over 50% of assistive equipment is abandoned by the patients due to poor fit between the patient and the assistive equipment. This paper explores clinician perceptions of an early stage three-dimensional measurement aid prototype, which provides enhanced assistive equipment provision process guidance to clinicians. Ten occupational therapists trialled the three-dimensional measurement aid prototype application; think-aloud and semi-structured interview data was collected...
August 1, 2017: Health Informatics Journal
https://www.readbyqxmd.com/read/28815764/aligning-digital-cd8-scoring-and-targeted-next-generation-sequencing-with-pd-l1-expression-a-pragmatic-approach-in-early-stage-squamous-cell-lung-carcinoma
#16
Esther Conde, Alejandra Caminoa, Carolina Dominguez, Antonio Calles, Stefan Walter, Barbara Angulo, Elena Sánchez, Marta Alonso, Luis Jimenez, Luis Madrigal, Florentino Hernando, Julian Sanz-Ortega, Beatriz Jimenez, Pilar Garrido, Luis Paz-Ares, Javier de Castro, Susana Hernandez, Fernando Lopez-Rios
AIMS: To study PD-L1 expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8(+) TILs were scored with a digital algorithm...
August 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28815629/impulsive-decision-making-in-young-adult-social-drinkers-and-detoxified-alcohol-dependent-patients-a-cross-sectional-and-longitudinal-study
#17
Nadine Bernhardt, Stephan Nebe, Shakoor Pooseh, Miriam Sebold, Christian Sommer, Julian Birkenstock, Ulrich S Zimmermann, Andreas Heinz, Michael N Smolka
BACKGROUND: Impulsive decision making relates to problematic substance use. Specifically, altered delay discounting has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting or loss aversion are clearly understudied. METHODS: Two studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of delay discounting, probability discounting for gains and losses, and loss aversion...
August 17, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28815296/autoantibodies-against-rods-and-rings-related-impdh2-in-hepatitis-c-genotype-1-and-daa-therapy-in-a-real-life-cohort
#18
Werner Dammermann, Susanne Polywka, Inga Dettmann, Swantje Mindorf, Lars Komorowski, Malte Wehmeyer, Julian Schulze Zur Wiesch, Winfried Stöcker, Stefan Lüth
Autoantibodies against inosine-5'-monophosphate-dehydrogenase-2 (IMPDH2; "rods and rings" pattern) develop in chronic hepatitis C (CHC) patients under treatment with peg-interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. We investigated the influence of the alternative therapy with direct-acting antivirals (DAA)/ribavirin on anti-IMPDH2 autoantibody generation and the use of anti-IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). We analyzed a "real life" cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV-treated CHC GT1 patients...
August 16, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28814497/extracellular-acid-base-balance-and-ion-transport-between-body-fluid-compartments
#19
REVIEW
Julian L Seifter, Hsin-Yun Chang
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment...
September 2017: Physiology
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#20
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
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