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https://www.readbyqxmd.com/read/28221865/cost-effectiveness-of-immune-checkpoint-inhibition-in-braf-wild-type-advanced-melanoma
#1
Christine G Kohn, Simon B Zeichner, Qiushi Chen, Alberto J Montero, Daniel A Goldstein, Christopher R Flowers
Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220108/adaptations-in-basal-and-hypothalamic-pituitary-adrenal-activated-deoxycorticosterone-responses-following-ethanol-self-administration-in-cynomolgus-monkeys
#2
Vanessa A Jimenez, Patrizia Porcu, A Leslie Morrow, Kathleen A Grant
Acute ethanol activates the hypothalamic-pituitary-adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28214176/sex-differences-in-prolactin-levels-in-emerging-psychosis-indication-for-enhanced-stress-reactivity-in-women
#3
Sarah Ittig, Erich Studerus, Ulrike Heitz, Stephanie Menghini-Müller, Katharina Beck, Laura Egloff, Letizia Leanza, Christina Andreou, Anita Riecher-Rössler
BACKGROUND: Hyperprolactinemia is a known side effect of antipsychotics. In recent reports it has also been shown in antipsychotic-naïve at-risk mental state (ARMS) and first-episode psychosis (FEP) patients. Prolactin is not only involved in reproduction and lactation, but is also synthesized in response to stress. As stress is thought to play an important role in the onset and relapse of schizophrenia, the aim of this study was to further elucidate the influence of prolactin in emerging psychosis...
February 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28203119/higher-phagocytic-activity-of-thioglycollate-elicited-peritoneal-macrophages-is-related-to-metabolic-status-of-the-cells
#4
Sofia Pavlou, Luxi Wang, Heping Xu, Mei Chen
BACKGROUND: Peritoneal macrophages are widely used in immunological studies. The cells can be collected under non-elicited (resident) or elicited (e.g., with Brewer thioglycollate broth injection) conditions, and their phenotype and functions differ. Recent studies have shown that macrophage phenotype and function are related to their metabolic states, and metabolic reprogramming has been an emerging concept for controlling macrophage function. In this study, we examined the metabolic state of resident and elicited macrophages and investigated how their metabolic state may affect cell function, including phagocytosis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28201920/atomic-vs-quantum-dot-open-shell-spectra
#5
Jacob Katriel, H E Montgomery
Hund's rules apply to pairs of atomic states which, in the limit of weak interelectronic repulsion, belong to a common configuration. We examine the asymptotic behavior of the energy difference between states belonging to such pairs (ΔE) as a function of the nuclear charge (Z) at both Z→∞ (ignoring relativistic effects) and at Z→Zc, where Zc is the critical charge below which the outermost electron is not bound. We find that the ratio ΔEZ(2) is non-monotonic, having a maximum at some intermediate value of Z...
February 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28198672/integrated-metagenomic-data-analysis-demonstrates-that-a-loss-of-diversity-in-oral-microbiota-is-associated-with-periodontitis
#6
Dongmei Ai, Ruocheng Huang, Jin Wen, Chao Li, Jiangping Zhu, Li Charlie Xia
BACKGROUND: Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. METHODS: A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28197805/economic-analysis-and-budget-impact-of-tenofovir-and-entecavir-in-the-first-line-treatment-of-hepatitis-b-virus-in-italy
#7
M Ruggeri, M Basile, S Coretti, C Drago, A Cicchetti
BACKGROUND: Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. The treatments of chronic hepatitis B cannot totally cure the disease but can prevent its progression to hepatocellular carcinoma, decreasing the levels of both morbidity and mortality. To date, there are several therapies indicated by the international guidelines as first-line treatments for the management of hepatitis B; two of the most effective are those based on either tenofovir or entecavir...
February 14, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/28195569/rare-damaging-variants-in-dna-repair-and-cell-cycle-pathways-are-associated-with-hippocampal-and-cognitive-dysfunction-a-combined-genetic-imaging-study-in-first-episode-treatment-naive-patients-with-schizophrenia
#8
Z Yang, M Li, X Hu, B Xiang, W Deng, Q Wang, Y Wang, L Zhao, X Ma, P C Sham, G Northoff, T Li
Schizophrenia is a complex neurodevelopmental disorder where changes in both hippocampus and memory-related cognitive functions are central. However, the exact relationship between neurodevelopmental-genetic factors and hippocampal-cognitive dysfunction remains unclear. The general aim of our study is to link the occurrence of rare damaging mutations involved in susceptibility gene pathways to the structure and function of hippocampus in order to define genetically and phenotypically based subgroups in schizophrenia...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28190681/differential-effects-of-metformin-on-age-related-comorbidities-in-older-men-with-type-2-diabetes
#9
Chen-Pin Wang, Carlos Lorenzo, Samy L Habib, Booil Jo, Sara E Espinoza
AIMS: To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality. METHODS: We identified a clinical cohort of male veterans in the United States who were ≥65years old with T2D and free from ARCs during 2002-2003...
January 28, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28187217/electrophysiological-cognitive-and-clinical-profiles-of-at-risk-mental-state-the-longitudinal-minds-in-transition-mint-study
#10
Rebbekah J Atkinson, W Ross Fulham, Patricia T Michie, Philip B Ward, Juanita Todd, Helen Stain, Robyn Langdon, Renate Thienel, Georgie Paulik, Gavin Cooper, Ulrich Schall
The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established...
2017: PloS One
https://www.readbyqxmd.com/read/28187216/the-lexicocalorimeter-gauging-public-health-through-caloric-input-and-output-on-social-media
#11
Sharon E Alajajian, Jake Ryland Williams, Andrew J Reagan, Stephen C Alajajian, Morgan R Frank, Lewis Mitchell, Jacob Lahne, Christopher M Danforth, Peter Sheridan Dodds
We propose and develop a Lexicocalorimeter: an online, interactive instrument for measuring the "caloric content" of social media and other large-scale texts. We do so by constructing extensive yet improvable tables of food and activity related phrases, and respectively assigning them with sourced estimates of caloric intake and expenditure. We show that for Twitter, our naive measures of "caloric input", "caloric output", and the ratio of these measures are all strong correlates with health and well-being measures for the contiguous United States...
2017: PloS One
https://www.readbyqxmd.com/read/28185094/abnormal-functional-connectivity-strength-in-patients-with-adolescent-onset-schizophrenia-a-resting-state-fmri-study
#12
Shuai Wang, Yajing Zhan, Yan Zhang, Luxian Lv, Renrong Wu, Jingping Zhao, Wenbin Guo
Structural and functional abnormalities were reported in the brain of patients with adolescent-onset schizophrenia (AOS). However, evidence of abnormal functional connectivity of the brain in AOS patients is limited. Thus, we analyzed the resting-state functional magnetic resonance scans of 48 drug-naive AOS patients and 31 healthy controls to determine their functional connectivity strength (FCS) and examined if FCS abnormalities were correlated with clinical characteristics. Compared with healthy controls, AOS patients showed significantly increased FCS in the left cerebellum VI and right inferior frontal gyrus/insula...
February 9, 2017: European Child & Adolescent Psychiatry
https://www.readbyqxmd.com/read/28183272/sepia-a-knowledge-driven-algorithm-for-predicting-conformational-b-cell-epitopes-from-the-amino-acid-sequence
#13
Georgios A Dalkas, Marianne Rooman
BACKGROUND: The identification of immunogenic regions on the surface of antigens, which are able to be recognized by antibodies and to trigger an immune response, is a major challenge for the design of new and effective vaccines. The prediction of such regions through computational immunology techniques is a challenging goal, which will ultimately lead to a drastic limitation of the experimental tests required to validate their efficiency. However, current methods are far from being sufficiently reliable and/or applicable on a large scale...
February 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28174249/tracking-the-embryonic-stem-cell-transition-from-ground-state-pluripotency
#14
Tüzer Kalkan, Nelly Olova, Mila Roode, Carla Mulas, Heather J Lee, Isabelle Nett, Hendrik Marks, Rachael Walker, Hendrik G Stunnenberg, Kathryn S Lilley, Jennifer Nichols, Wolf Reik, Paul Bertone, Austin Smith
Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here we examined the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28174129/intrinsic-cerebral-activity-at-resting-state-in-adults-with-major-depressive-disorder-a-meta-analysis
#15
Ming Zhou, Xinyu Hu, Lu Lu, Lianqing Zhang, Lizhou Chen, Qiyong Gong, Xiaoqi Huang
Numerous neuroimaging studies have been undertaken to detect cerebral intrinsic activity in major depressive disorder (MDD) with resting state fMRI (rs-fMRI). However, the inconsistent results have hindered our understanding of the exact neuropathology related to MDD. The current meta-analysis used state-of-the-art conjunction analysis techniques to systematically review and summarize all available neuroimaging studies using rs-fMRI with amplitude of low frequency fluctuation (ALFF) and/or fractional ALFF (fALFF) on MDD patients and further explored the effect of antidepressants on the intrinsic activity of the brain...
February 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28172657/op025-evaluation-of-adalimumab-effectiveness-in-anti-tumor-necrosis-factor-na%C3%A3-ve-pediatric-patients-with-crohn-s-disease-in-clinical-practice
#16
S Steiner, E King, K Park, D Pashankar, H Shashidhar, B Sudel, S Eichner, S Chen, J Pratt, R Colletti
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28169971/health-related-quality-of-life-in-pediatric-patients-with-chronic-hepatitis-b-living-in-the-united-states-and-canada
#17
Sarah Jane Schwarzenberg, Simon C Ling, Yona Keich Cloonan, Hsing-Hua S Lin, Donna M Evon, Karen F Murray, Norberto Rodriguez-Baez, Philip Rosenthal, Jeffrey Teckman, Kathleen B Schwarz
OBJECTIVES: To determine if selected socio-demographic and HBV-specific clinical factors are associated with health-related quality of life (HRQoL) among pediatric patients chronically infected with hepatitis B virus (HBV). METHODS: Children with chronic HBV enrolled in the Hepatitis B Research Network completed the Child Health Questionnaire (CHQ) at study entry. Caregivers of children 5- < 10 years completed the parent-reported PF50; youth 10- < 18 years completed the child-reported CF87...
February 4, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28169326/novel-peptides-for-deciphering-structural-and-signalling-functions-of-e-cadherin-in-mouse-embryonic-stem-cells
#18
Joe M Segal, Christopher M Ward
We have previously shown that E-cadherin regulates the naive pluripotent state of mouse embryonic stem cells (mESCs) by enabling LIF-dependent STAT3 phosphorylation, with E-cadherin null mESCs exhibiting over 3000 gene transcript alterations and a switch to Activin/Nodal-dependent pluripotency. However, elucidation of the exact mechanisms associated with E-cadherin function in mESCs is compounded by the difficulty in delineating the structural and signalling functions of this protein. Here we show that mESCs treated with the E-cadherin neutralising antibody DECMA-1 or the E-cadherin binding peptide H-SWELYYPLRANL-NH2 (Epep) exhibit discrete profiles for pluripotent transcripts and NANOG protein expression, demonstrating that the type of E-cadherin inhibitor employed dictates the cellular phenotype of mESCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152950/brentuximab-vedotin-in-relapsed-refractory-hodgkin-lymphoma-following-autologous-stem-cell-transplant-a-cost-effectiveness-analysis-updated-with-5-year-follow-up-data-from-the-pivotal-trial
#19
Gemma Kay, Esprit Ma, Beth Woods, James Eaton, Peter Sajosi, Andreas Engstrom, Ross Selby, Eugene Benson, Jeremy Teasell, Akshara Richhariya, Andrew Briggs, Vijayveer Bonthapally
: 19 Background: In 2015, the Scottish Medicines Consortium (SMC) made a positive recommandation for brentuximab vedotin (BV) in patients with relapsed or refractory (R/R) Hodgkin lymphoma (HL) who have received autologous stem cell transplantation (ASCT) based on 3-year follow-up data from the pivotal phase 2 single-arm trial (SG035-0003; NCT00848926). At 3-years, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin compared with chemotherapy +/- radiotherapy (C/R) was £43,731 per quality-adjusted life year (QALY)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28150133/impact-of-age-and-polytherapy-on-fingolimod-induced-bradycardia-a-preclinical-study
#20
Christian Ritter, Martin K R Svačina, Ilja Bobylev, Abhijeet Joshi, Toni Schneider, Helmar C Lehmann
Fingolimod is a an oral disease modifying drug for relapsing remitting multiple sclerosis (MS) preventing egress of B and T cells from lymph nodes. Relevant first dose adverse events include bradycardia and atrioventricular conduction slowing. Cardiac side effects of fingolimod and combinational pharmacotherapy including duloxetine and tolterodine were monitored in mice of different age using implantable ECG telemetric systems. Cardiac tissue was assessed for S1P-receptor subtype (1 and 3), and for GIRK1 expression...
February 1, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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