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141.
Robert Mason Helen C. Dearden Bella Nguyen Jennifer A. Soon Jessica Louise Smith Manreet Randhawa Andrew Mant Lydai Warburton Serigne Lo Tarek Meniawy Alexander Guminski Phillip Parente Sayed Ali Andrew Haydon Georgina V. Long Matteo S. Carlino Michael Millward Victoria G. Atkinson Alexander M. Menzies 《Pigment cell & melanoma research》2020,33(2):358-365
The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response. 相似文献
142.
Abdullah Al Emran Hsin‐Yi Tseng Mikaela C. Coleman Jessamy Tiffen Stuart Cook Helen M. McGuire Stuart Gallagher Carl Feng Peter Hersey 《Pigment cell & melanoma research》2020,33(5):660-670
Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms. 相似文献
143.
Cora E. Lewis John P. Bantle Alain G. Bertoni George Blackburn Frederick L. Brancati George A. Bray Lawrence J. Cheskin Jeffrey M. Curtis Caitlin Egan Mary Evans John P. Foreyt Siran Ghazarian Bethany Barone Gibbs Stephen P. Glasser Edward W. Gregg Helen P. Hazuda Louise Hesson James O. Hill Edward S. Horton Van S. Hubbard John M. Jakicic Robert W. Jeffery Karen C. Johnson Steven E. Kahn Abbas E. Kitabchi Dalane Kitzman William C. Knowler Edward Lipkin Sara Michaels Maria G. Montez David M. Nathan Ebenezer Nyenwe Jennifer Patricio Anne Peters Xavier Pi‐Sunyer Henry Pownall David M. Reboussin Donna H. Ryan Thomas A. Wadden Lynne E. Wagenknecht Holly Wyatt Rena R. Wing Susan Z. Yanovski 《Obesity (Silver Spring, Md.)》2020,28(2):247-258
144.
Ariana M. Chao Thomas A. Wadden Robert I. Berkowitz George Blackburn Paula Bolin Jeanne M. Clark Mace Coday Jeffrey M. Curtis Linda M. Delahanty Gareth R. Dutton Mary Evans Linda J. Ewing John P. Foreyt Linda J. Gay Edward W. Gregg Helen P. Hazuda James O. Hill Edward S. Horton Denise K. Houston John M. Jakicic Robert W. Jeffery Karen C. Johnson Steven E. Kahn William C. Knowler Anne Kure Katherine L. Michalski Maria G. Montez Rebecca H. Neiberg Jennifer Patricio Anne Peters Xavier Pi‐Sunyer Henry Pownall David Reboussin Bruce Redmon W. Jack Rejeski Helmut Steinburg Martha Walker Donald A. Williamson Rena R. Wing Holly Wyatt Susan Z. Yanovski Ping Zhang 《Obesity (Silver Spring, Md.)》2020,28(5):893-901
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146.
Philip Lavretsky Nancy Rotzel McInerney Jonathon E. Mohl Joshua I. Brown Helen F. James Kevin G. McCracken Robert C. Fleischer 《Molecular ecology》2020,29(3):578-595
Along with manipulating habitat, the direct release of domesticated individuals into the wild is a practice used worldwide to augment wildlife populations. We test between possible outcomes of human‐mediated secondary contact using genomic techniques at both historical and contemporary timescales for two iconic duck species. First, we sequence several thousand ddRAD‐seq loci for contemporary mallards (Anas platyrhynchos) throughout North America and two domestic mallard types (i.e., known game‐farm mallards and feral Khaki Campbell's). We show that North American mallards may well be becoming a hybrid swarm due to interbreeding with domesticated game‐farm mallards released for hunting. Next, to attain a historical perspective, we applied a bait‐capture array targeting thousands of loci in century‐old (1842–1915) and contemporary (2009–2010) mallard and American black duck (Anas rubripes) specimens. We conclude that American black ducks and mallards have always been closely related, with a divergence time of ~600,000 years before present, and likely evolved through prolonged isolation followed by limited bouts of gene flow (i.e., secondary contact). They continue to maintain genetic separation, a finding that overturns decades of prior research and speculation suggesting the genetic extinction of the American black duck due to contemporary interbreeding with mallards. Thus, despite having high rates of hybridization, actual gene flow is limited between mallards and American black ducks. Conversely, our historical and contemporary data confirm that the intensive stocking of game‐farm mallards during the last ~100 years has fundamentally changed the genetic integrity of North America's wild mallard population, especially in the east. It thus becomes of great interest to ask whether the iconic North American mallard is declining in the wild due to introgression of maladaptive traits from domesticated forms. Moreover, we hypothesize that differential gene flow from domestic game‐farm mallards into the wild mallard population may explain the overall temporal increase in differentiation between wild black ducks and mallards, as well as the uncoupling of genetic diversity and effective population size estimates across time in our results. Finally, our findings highlight how genomic methods can recover complex population histories by capturing DNA preserved in traditional museum specimens. 相似文献
147.
148.
Michael A.P. Bloomfield Tinya Chang Maximillian J. Woodl Laura M. Lyons Zhen Cheng Clarissa Bauer‐Staeb Catherine Hobbs Sophie Bracke Helen Kennerley Louise Isham Chris Brewin Jo Billings Talya Greene Glyn Lewis 《World psychiatry》2021,20(1):107-123
Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psychological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis. 相似文献
149.
Santos Francisco Denis Souza Maubrigades Lucas Reichert Gonçalves Vitória Sequeira Franz Helen Cabaldi Rodrigues Paulo Ricardo Centeno Cunha Rodrigo Casquero Leite Fábio Pereira Leivas 《Probiotics and antimicrobial proteins》2021,13(3):655-663
Probiotics and Antimicrobial Proteins - Bacterial spores of the genus Bacillus are being evaluated as adjuvant molecules capable of improving the immune response to vaccines. In this study, we... 相似文献
150.
Helen Ngum Ntonifor Julius Suh Chewa Mahamat Oumar Hermann Desire Mbouobda 《PLoS neglected tropical diseases》2021,15(3)
This study aimed at determining the impact of intestinal helminths on malaria parasitaemia, anaemia and pyrexia considering the levels of IL-1β among outpatients in Bamenda. A cohort of 358 consented participants aged three (3) years and above, both males and females on malaria consultation were recruited in the study. At enrolment, patients’ axillary body temperatures were measured and recorded. Venous blood was collected for haemoglobin concentration and malaria parasitaemia determination. Blood plasma was used to measure human IL-1β levels using Human ELISA Kit. The Kato-Katz technique was used to process stool samples. Five species of intestinal helminths Ascaris lumbricoides (6.4%), Enterobius vermicularis (5.0%), Taenia species (4.2%), Trichuris trichiura (1.1%) and hookworms (0.8%) were identified. The overall prevalence of Plasmodium falciparum and intestinal helminths was 30.4% (109/358) and 17.6% (63/358) respectively. The prevalence of intestinal helminths in malaria patients was 17.4% (19/109). Higher Geometric mean parasite density (GMPD ±SD) (malaria parasitaemia) was significantly observed in patients co-infected with Enterobius vermicularis (5548 ± 2829/μL, p = 0.041) and with Taenia species (6799 ± 4584/μL, p = 0.020) than in Plasmodium falciparum infected patients alone (651 ± 6076/ μL). Higher parasitaemia of (1393 ± 3031/μL) and (3464 ± 2828/μL) were recorded in patients co-infected with Ascaris lumbricoides and with hookworms respectively but the differences were not significant (p > 0.05). Anaemia and pyrexia prevalence was 27.1% (97/358) and 33.5% (120/358) respectively. Malaria patients co-infected with Enterobius vermicularis and Ascaris lumbricoides had increased risk of anaemia (OR = 13.712, p = 0.002 and OR = 16.969, p = 0.014) respectively and pyrexia (OR = 18.07, p = 0.001 and OR = 22.560, p = 0.007) respectively than their counterparts. Increased levels of IL-1β were significantly observed in anaemic (148.884 ± 36.073 pg/mL, t = 7.411, p = 0.000) and pyretic (127.737 ± 50.322 pg/mL, t = 5.028, p = 0.000) patients than in non-anaemic (64.335 ± 38.995pg/mL) and apyretic patients (58.479 ± 36.194pg/mL). Malaria patients co-infected with each species of intestinal helminths recorded higher IL-1β levels (IL-1β > 121.68 ± 58.86 pg/mL) and the overall mean (139.63 ± 38.33pg/mL) was higher compared with levels in malaria (121.68 ± 58.86 pg/mL) and helminth (61.78 ± 31.69pg/mL) infected patients alone. Intestinal helminths exacerbated the clinical outcomes of malaria in the patients and increased levels of IL-1β were observed in co-infected patients with anaemia, pyrexia and higher parasitaemia. 相似文献