bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of transcatheter arterial chemoembolization with embospheres in treatment of hepatocellular carcinoma
Authors: Hao Ming Zhi , Lin Hai Lan , Chen Qi Zhong , Hu Yu Bin , Chen Jian Bin , Zheng Jian Xiong , Zhou Dong , Zhang Hui 
Published: December 2016

ObjectiveTo investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE) with embospheres for the treatment of unresectable hepatocellular carcinoma (HCC).MethodsPatients with unresectable HCC who were treated with TACE followed by embosphere treatment (Embo‐TACE) or conventional TACE (cTACE) between May 2010 and March 2014 were retrospectively included in this study. The Embo‐TACE group received lipiodol and chemotherapeutic agent emulsion, followed by embospheres. The cTACE group received lipiodol and chemotherapeutic agent emulsion, followed by gelatin sponge pellets. Time to progression (TTP), overall survival (OS), overall response rate (ORR), and safety were compared between the two groups. Univariate and multivariate regression analyses of the factors affecting survival were conducted.ResultsThe median TTP and OS in the Embo‐TACE group were significantly longer than those in the cTACE group (TPP: 7.0 months vs 5.4 months, P = 0.035; OS: 15 months vs 12 months, P = 0.032). Seven days after the first TACE treatment, alanine aminotransferase level was higher in the cTACE group than in the Embo‐TACE group (P = 0.015). The ORR did not significantly differ between the two groups (P = 0.827). Additional therapy and local responses one month after the first TACE treatment were associated with OS.ConclusionsEmbo‐TACE resulted in a significant improvement in TTP and OS for patients with unresectable HCC, compared with cTACE. Furthermore, Embo‐TACE was better tolerated. Additional therapy and local responses one month after the first TACE were independent prognostic factors for OS.
Insulin treatment restores islet microvascular vasomotion function in diabetic mice
Authors: Liu Mingming , Zhang Xiaoyan , Li Ailing , Zhang Xu , Wang Bing , Li Bingwei , Liu Shuying , Li Hongwei , Xiu Ruijuan 
Published: December 2016

AbstractBackgroundThe microcirculation plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that pancreatic islet microvascular (PIM) vasomotion, as a parameter of pancreatic islet microcirculation function, is abnormal in diabetic mice and that insulin treatment may reverse this dysfunction.MethodsMice were randomly assigned to non‐diabetic control, untreated diabetic, and insulin‐treated diabetic groups (n = 6 in each group). Separate groups of streptozotocin (STZ)‐induced diabetic and high‐fat diet‐fed mice were used as a model of hyperglycemia. Insulin‐treated diabetic mice were treated with 1–1.5 IU/day insulin for 1 week. Laser Doppler monitors were used to evaluate PIM vasomotion. Morphological and ultrastructural changes in islet endothelial cells were determined by immunohistochemistry and transmission electron microscopy. Glucagon, insulin, vascular endothelial growth factor (VEGF)‐A, and platelet endothelial cell adhesion molecule (PECAM‐1) expression was determined by immunohistochemistry and Western blotting.ResultsIn both untreated diabetic groups, the pancreatic islet microcirculation was unable to regulate PIM vasomotion. The rhythm of vasomotion was irregular, and the average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower than in non‐diabetic controls. Insulin treatment restored the functional status of PIM vasomotion. In islet endothelial cells from both untreated diabetic groups, the mitochondria were swollen with disarrangement of the cristae, and the distribution of PECAM‐1 was discontinuous. Insulin treatment significantly increased the reduced expression of PECAM‐1 in both untreated diabetic groups and VEGF‐A expression in untreated STZ‐diabetic mice.ConclusionThe results suggest that the functional status of PIM vasomotion is impaired in diabetic mice but can be restored by insulin.
The role of imaging in the surveillance and diagnosis of hepatocellular cancer
Authors: Dulku Gurjeet , Dhillon Ravinder , Goodwin Mark , Cheng Wendy , Kontorinis Nick , Mendelson Richard 
Published: December 2016

SummaryA decision support tool has been developed as part of a suite of on‐line evidence‐based and consensus‐based guidelines Diagnostic imaging Pathways (DIP): www.imagingpathways.health.wa.gov.au) in the form of an algorithmic flow chart with supporting evidence and consensus to inform referrers to diagnostic imaging and radiologists as to the optimum strategy for surveillance and diagnosis of primary hepatocellular cancer (HCC) in those patients with risk factors of this disease. A literature review, including reference to several international consensus‐based expert guidelines, has been employed to develop this tool.
Radiation Oncology research grants awarded by the Royal Australian and New Zealand College of Radiologists: Value for money?
Authors: Roos Daniel E , Kartika Joshua K , Hu Marcus Q 
Published: December 2016

AbstractIntroductionThe Royal Australian and New Zealand College of Radiologists (RANZCR) and other medical colleges have provided research grants from their budgets for many years. This survey‐based project aimed to determine whether the RANZCR Faculty of Radiation Oncology (FRO) is realizing value for money from its seed funding, and to compare this with grant activities of the other colleges.MethodsEligible FRO grant recipients between 1999 and 2014 were surveyed regarding bibliometric data, subjective outcomes and factors considered important in completing their research projects. The other colleges were also approached via email and phone interviews.ResultsA records search identified 26 eligible individuals who received 42 grants for 41 projects. The survey response rate was 100%, identifying 33 secondary grants, 65 conference presentations, 10 prizes and 69 publications associated with the FRO grants and consequential research. At least seven higher degrees also resulted. The funding process was very positively perceived by grant recipients, and the two factors identified as most important in project completion were local infrastructure and RANZCR funding. In 2015, FRO allocated AUD$150K for grants compared with $10K–$2.6M from 10 of the other 15 Australasian Medical Colleges. In general, appraisal of funding outcomes relative to expenditure has been only low level until recently.ConclusionsThis project has identified significant research output and subjective benefit from relatively modest FRO seed grants, implying a favourable cost‐benefit ratio. Such outcomes monitoring needs to be more widely pursued within Australasian medical colleges.
Partial Protection by Dietary Antioxidants Against Ethanol‐Induced Osteopenia and Changes in Bone Morphology in Female Mice
Authors: Alund Alexander W. , Mercer Kelly E. , Pulliam Casey F. , Suva Larry J. , Chen Jin‐Ran , Badger Thomas M. , Ronis Martin J. J. 
Published: December 2016

BackgroundChronic alcohol consumption leads to increased fracture risk and an elevated risk of osteoporosis by decreasing bone accrual through increasing osteoclast activity and decreasing osteoblast activity. We have shown that this mechanism involves the generation of reactive oxygen species (ROS) produced by NADPH oxidases. It was hypothesized that different dietary antioxidants, N‐acetyl cysteine (NAC; 1.2 mg/kg/d), and α‐tocopherol (Vit.E; 60 mg/kg/d) would be able to attenuate the NADPH oxidase‐mediated ROS effects on bone due to chronic alcohol intake.MethodsTo study the effects of these antioxidants, female mice received a Lieber–DeCarli liquid diet containing ethanol (EtOH) with or without additional antioxidant for 8 weeks.ResultsTibias displayed decreased cortical bone mineral density in both the EtOH and EtOH + antioxidant groups compared to pair‐fed (PF) and PF + antioxidant groups (p < 0.05). However, there was significant protection from trabecular bone loss in mice fed either antioxidant (p < 0.05). Microcomputed tomography analysis demonstrated a significant decrease in bone volume (bone volume/tissue volume) and trabecular number (p < 0.05), along with a significant increase in trabecular separation in the EtOH compared to PF (p < 0.05). In contrast, the EtOH + NAC and EtOH + Vit.E did not statistically differ from their respective PF controls. Ex vivo histologic sections of tibias were stained for nitrotyrosine, an indicator of intracellular damage by ROS, and tibias from mice fed EtOH exhibited significantly more staining than PF controls. EtOH treatment significantly increased the number of marrow adipocytes per mm as well as mRNA expression of aP2, an adipocyte marker in bone. Only NAC was able to reduce the number of marrow adipocytes to PF levels. EtOH‐fed mice exhibited reduced bone length (p < 0.05) and had a reduced number of proliferating chondrocytes within the growth plate. NAC and Vit.E prevented this (p < 0.05).ConclusionsThese data show that alcohol's pathological effects on bone extend beyond decreasing bone mass and suggest a partial protective effect of the dietary antioxidants NAC and Vit.E at these doses with regard to alcohol effects on bone turnover and bone morphology.
A novel bispecific DARPin targeting FcγRIIB and FcεRI‐bound IgE inhibits allergic responses
Authors: Zellweger F. , Gasser P. , Brigger D. , Buschor P. , Vogel M. , Eggel A. 
Published: December 2016

AbstractBackgroundBinding of allergen‐specific IgE to its high‐affinity receptor FcεRI on basophils and mast cells is a central event in the development of allergies. Exposure of these cells to allergens induces the release of soluble mediators causing allergic symptoms. The inhibitory low‐affinity IgG Fc‐receptor FcγRIIB is co‐expressed on allergic effector cells and has been implicated in negative regulation of immediate hypersensitivity responses. In order to harvest the inhibitory function of this receptor, we aimed to select specific binders against FcγRIIB and to generate a bispecific molecule simultaneously targeting FcγRIIB and FcεRI‐bound IgE on the surface of allergic effector cells.MethodsWe selected FcγRIIB‐specific binding molecules from a library of designed ankyrin repeat proteins using ribosome display technology. The bispecific binding modality was generated by molecular cloning and recombinant protein expression. We determined binding characteristics on molecular and cellular levels using SPR, ELISA, and flow cytometry. The inhibitory potential of the newly described molecules was assessed in different cellular degranulation assays ex vivo and in a mouse model of passive systemic anaphylaxis.ResultsWe demonstrate that the selected DARPin® proteins recognize FcγRIIB with high affinity. Furthermore, the bispecific binding protein successfully interferes with allergen‐induced cell degranulation and efficiently inhibits systemic anaphylaxis in vivo. Mechanistically, we report that FcγRIIB‐mediated inhibition of effector cell activation requires direct ligation to an activating FcεRI receptor.ConclusionThe described bispecific DARPin protein has the ability to co‐ligate FcγRIIB with FcεRI‐bound IgE on allergic effector cells and represents an efficient dual‐modality to interfere with allergic hypersensitivity reactions.
The effect of physical fatigue on oscillatory dynamics of the sensorimotor cortex
Authors: Fry A. , Mullinger K. J. , O'Neill G. C. , Brookes M. J. , Folland J. P. 
Published: December 2016

AbstractAimWhile physical fatigue is known to arise in part from supraspinal mechanisms within the brain, exactly how brain activity is modulated during fatigue is not well understood. Therefore, this study examined how typical neural oscillatory responses to voluntary muscle contractions were affected by fatigue.MethodsEleven healthy adults (age 27 ± 4 years) completed two experimental sessions in a randomized crossover design. Both sessions first assessed baseline maximal voluntary isometric wrist‐flexion force (MVFb). Participants then performed an identical series of fourteen test contractions (2 × 100%MVFb, 10 × 40%MVFb, 2 × 100%MVFb) both before and after one of two interventions: forty 12‐s contractions at 55%MVFb (fatigue intervention) or 5%MVFb (control intervention). Magnetoencephalography (MEG) was used to characterize both the movement‐related mu and beta decrease (MRMD and MRBD) and the post‐movement beta rebound (PMBR) within the contralateral sensorimotor cortex during the 40%MVFb test contractions, while the 100%MVFb test contractions were used to monitor physical fatigue.ResultsThe fatigue intervention induced a substantial physical fatigue that endured throughout the post‐intervention measurements (28.9–29.5% decrease in MVF, P < 0.001). Fatigue had a significant effect on both PMBR (anova, session × time‐point interaction: P = 0.018) and MRBD (P = 0.021): the magnitude of PMBR increased following the fatigue but not the control interventions, whereas MRBD was decreased post‐control but not post‐fatigue. Mu oscillations were unchanged throughout both sessions.ConclusionPhysical fatigue resulted in an increased PMBR, and offset attenuations in MRBD associated with task habituation.
Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats
Authors: Bi Mingjun , Li Qin , Guo Dadong , Ding Xiaoyu , Bi Weikang , Zhang Yueheng , Zou Yong 
Published: December 2016

AbstractCarbon monoxide (CO) poisoning is one of the leading causes of toxicity‐related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC‐1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and thioredoxin‐1 (Trx‐1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle‐dose or high‐dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.
Ublituximab (TG‐1101), a novel glycoengineered anti‐CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial
Authors: Sharman Jeff P. , Farber Charles M. , Mahadevan Daruka , Schreeder Marshall T. , Brooks Heather D. , Kolibaba Kathryn S. , Fanning Suzanne , Klein Leonard , Greenwald Daniel R. , Sportelli Peter , Miskin Hari P. , Weiss Michael S. , Burke John M. 
Published: December 2016

SummaryIbrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti‐CD20 monoclonal antibody with single‐agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2–6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty‐one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high‐risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long‐term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).
Outcomes of primary refractory diffuse large B‐cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era
Authors: Vardhana Santosha A. , Sauter Craig S. , Matasar Matthew J. , Zelenetz Andrew D. , Galasso Natasha , Woo Kaitlin M. , Zhang Zhigang , Moskowitz Craig H. 
Published: December 2016

SummaryRituximab‐containing salvage chemotherapy followed by high‐dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B‐cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first‐line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant‐eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high‐dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3‐year overall and progression‐free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long‐term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high‐dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.
Li‐Fraumeni syndrome: a paradigm for the understanding of hereditary cancer predisposition
Authors: Valdez Jessica M. , Nichols Kim E. , Kesserwan Chimene 
Published: December 2016

SummaryLi‐Fraumeni syndrome (LFS) is a rare cancer predisposing condition caused by germline mutations in TP53, the gene encoding the TP53 transcription factor. LFS is typified by the development of a wide spectrum of childhood and adult‐onset malignancies, which includes, among others, the lymphoid and myeloid leukaemias, myelodysplastic syndrome and, to a lesser extent, lymphoma. Accordingly, it is important that haematologists/oncologists be familiar with this pleiotropic hereditary cancer syndrome. The high cancer risk and variability in type and age of cancer onset have raised questions about the underlying biology and optimal treatment approaches for individuals with LFS. Since its description almost 50 years ago, many clinical and basic research investigations have provided insights into the pathogenesis, manifestations, genetic testing and management strategies for individuals with LFS. Here we provide an update on the current state of knowledge regarding LFS with an emphasis, where possible, on information relevant to practicing haematologists.
The promise of chimeric antigen receptor T cells (CARTs) in leukaemia
Authors: Orlowski Robert J. , Porter David L. , Frey Noelle V. 
Published: December 2016

SummaryThe success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, but also in maintaining long‐term disease control, has been unprecedented. While the foundation for this approach has been firmly set in place, continued development will improve the efficacy, toxicity and applicability to other malignancies of this new class of ‘living drugs’. In this review, we provide a comprehensive overview of the most current clinical trial data in both acute and chronic leukaemias, and discuss some of the potential ways to enhance the activity and safety of CART therapy going forward.
Perturbations environnementales et migrations au Vietnam
Authors: Haemmerli Guillaume , Bélanger Danièle , Fleury Charles , Bich Ngoc Luu 
Published: December 2016

Faits saillants

Les perturbations environnementales ne sont pas un facteur significatif de la migration au sein des ménages au Vietnam.
L'analyse multivariée montre que les caractéristiques socioéconomiques sont les facteurs les plus importants pour expliquer la propension à migrer suite à un évènement climatique extrême.
Une contradiction apparait entre la perception subjective de l'impact des évènements climatiques et leurs effets mesurés par des variables objectives.
Environmental tobacco smoke exposure and periodontitis prevalence among nonsmokers in the hispanic community Health Study/Study of Latinos
Authors: Akinkugbe Aderonke A. , Sanders Anne E. , Preisser John S. , Cai Jianwen , Salazar Christian R. , Beck James D. 
Published: December 2016

AbstractObjectiveTo describe self‐reported exposure to environmental tobacco smoke (ETS) and its association with periodontitis prevalence in a diverse group of Hispanics/Latinos.MethodsData came from 8675 lifetime nonsmokers in the 2008–2011 Hispanic Community Health Study/Study of Latinos. Exposure to ETS was self‐reported, while periodontitis was defined using the Centers for Disease Control and Prevention‐American Academy of Periodontology criteria and the proportion of sites affected by clinical attachment level of ≥3 mm or pocket depth of ≥4 mm. Survey logistic regression estimated prevalence odds ratios (POR) and 95% confidence intervals (CI). In addition, we assessed whether greater hours of exposure to ETS in the past year was associated with greater periodontitis prevalence, and lastly, we conducted a simple sensitivity analysis of ETS misclassification.ResultsAge‐standardized prevalence estimates (95% CI) for ETS exposure and periodontitis were 57.6% (55.9, 59.4) and 39.8% (38.1, 41.4), respectively. After adjusting for confounders and periodontitis risk factors, we estimated an overall adjusted POR (95% CI) for the ETS–periodontitis association as 1.09 (0.95–1.26) with a confidence limit ratio (CLR) of 1.34. This association varied in magnitude by Hispanic/Latino background, ranging from 1.04 (0.75, 1.43 with a CLR = 1.91) among Central Americans to 1.76 (1.16, 2.66 with a CLR = 2.29) in Puerto Ricans.ConclusionsPreviously reported associations between ETS and periodontitis appear weak in this study. However, the magnitude of the association differs according to Hispanic/Latino background.