bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endostar (rh‐endostatin) versus placebo in combination with vinorelbine plus cisplatin chemotherapy regimen in treatment of advanced non‐small cell lung cancer: A meta‐analysis
Authors: An Jihong , Lv Weiling 
Published: March 2018

BackgroundThis meta‐analysis was conducted to investigate the efficacy and safety of Endostar (rh‐endostatin) versus a placebo in combination with a vinorelbine plus cisplatin (NP) chemotherapy regimen for the treatment of advanced non‐small cell lung cancer (NSCLC).MethodsTwo reviewers independently searched Medline, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, ASCO, ESMO, the Web of Science, and CNKI databases to locate relevant controlled clinical trials. The treatment efficacy and drug‐related toxicity of NP + Endostar (NPE) and NP groups were pooled through meta‐analysis according to random or fixed effect models.ResultsFifteen prospective clinical studies were included in this meta‐analysis. The pooled risk ratio (RR) for objective response rate was 1.74 (95% confidence interval [CI] 1.43–2.11); the objective response rate in the NPE group was significantly higher than in the NP group (P < 0.05). Nine publications evaluated the incidence of leucopenia between Endostar versus a placebo in combination with an NP chemotherapy regimen. The pooled results showed no statistically significant difference between NPE and NP chemotherapy regimens for leucopenia, thrombocytopenia, and nausea/vomiting risk (P > 0.05). The one‐year survival rate in the NPE group was higher than in the NP group, with a statistically significant difference (RR = 1.70, 95% CI 1.07–2.89; P < 0.05).ConclusionEndostar combined with an NP chemotherapy regimen can improve the prognosis of patients with advanced NSCLC without increasing the risk of toxicity.
Analysis of the activity and safety of weekly low‐dose bevacizumab‐based regimens in heavily pretreated patients with metastatic breast cancer
Authors: Zhai Xiaoyu , Hong Ruoxi , Fan Ying , Yuan Peng , Wang Jiayu , Sang Die , Chen Junlin , Zhao Chunying , Ou Kaiping , Ma Fei , Xu Binghe 
Published: March 2018

BackgroundCurrently, there are no standard regimens for metastatic breast cancer patients (MBC) who have failed ≥ 3 chemotherapy treatments. The aim of this study was to assess whether weekly low‐dose bevacizumab‐based regimens were well tolerated and would improve efficacy in MBC patients who had failed numerous therapies.MethodsSeventeen patients with MBC who were heavily pretreated with a median of five regimens of therapy (range 1–10) between 2012 and 2016 were included in the analysis. Bevacizumab was administered at a dose of 100 mg intravenously once a week combined with one or two types of chemotherapeutic drugs until confirmed disease progression or an intolerable adverse event was observed. Patient characteristics, objective response rate, clinical benefit rate, progression‐free survival, and toxicity were assessed.ResultsAll 17 patients had been pretreated with taxane‐based and anthracycline‐based chemotherapy. Weekly low‐dose bevacizumab combined with one or two types of chemotherapeutic drugs, which had usually not been previously used (e.g. etoposide, irinotecan, pemetrexed, methotrexate, and nab‐paclitaxel), was administered. Three patients achieved a partial response, while one had stable disease for > 24 weeks, and the clinical benefit rate was 23.5%. Median progression‐free survival was 3.4 months (95% confidence interval 2.0–4.8). The most common hematological adverse events were neutropenia, anemia, and thrombocytopenia. Bevacizumab‐related adverse events included grade 1 bleeding (17.6%) and grade 2 hypertension (5.9%).ConclusionsWeekly low‐dose bevacizumab combined with chemotherapy shows a relatively favorable clinical response and tolerable toxicity, providing a feasible option for heavily pretreated MBC patients.
Integrating auxiliary data in optimal spatial design for species distribution modelling
Authors: Reich Brian J. , Pacifici Krishna , Stallings Jonathan W. 
Published: March 2018

AbstractTraditional surveys used to create species distribution maps and estimate ecological relationships are expensive and time consuming. Citizen science offers a way to collect a massive amount of data at negligible cost and has been shown to be a useful supplement to traditional analyses. However, there remains a need to conduct formal surveys to firmly establish ecological relationships and trends.In this paper, we investigate the use of auxiliary (e.g. citizen science) data as a guide to designing more efficient ecological surveys. Our aim is to explore the use of opportunistic data to inform spatial survey design through a novel objective function that minimizes misclassificaton rate (i.e. false positives and false negatives) of the estimated occupancy maps. We use an initial occupancy estimate from auxiliary data as the prior in a Bayesian spatial occupancy model, and an efficient posterior approximation that accounts for spatial dependence, covariate effects, and imperfect detection in an exchange algorithm to search for the optimal set of sampling locations to minimize misclassification rate.We examine the optimal design as a function of the detection rate and quality of the citizen‐science data, and compare this optimal design with several common ad hoc designs via an extensive simulation study. We then apply our method to eBird data for the brown‐headed nuthatch in the Southeast US.We argue that planning a survey with the use of auxiliary data improves estimation accuracy and may significantly reduce the costs of sampling.
Cerebrovascular autoregulation monitoring and patient‐centred outcomes after cardiac surgery: a systematic review
Authors: Chan B. , Butler E. , Frost S. A. , Chuan A. , Aneman A. 
Published: March 2018

BackgroundImpaired cerebrovascular autoregulation (CVAR) is observed in up to 20% of cardiac surgical patients. This systematic review aims to evaluate the association between impaired CVAR, measured by current monitoring techniques, and patient‐centred outcomes in adults following cardiac surgery.MethodsMEDLINE, EMBASE, PubMed, MEDLINE In‐Process and Cochrane Library were systematically searched through 8 December 2017. Studies were included if they assessed associations between CVAR and patient‐centred outcomes in the adult cardiac surgical population. The primary outcome of this systematic review was mortality. Secondary outcomes were stroke, delirium and acute kidney injury. Risk of bias was systematically assessed, and the GRADE methodology was used to evaluate the quality of evidence across outcomes.ResultsEleven observational studies and no randomised controlled trials met the inclusion criteria. Due to methodological heterogeneity, meta‐analysis was not possible. There was a high risk of bias within individual studies and low quality of evidence across outcomes. Of the included studies, one assessed mortality, five assessed stroke, four assessed delirium, and three assessed acute kidney injury. No reliable conclusions can be drawn from the one study assessing mortality. Interpretation of studies investigating CVAR and stroke, delirium and acute kidney injury was complicated by the lack of standardisation of monitoring techniques as well as varying definitions of impaired CVAR.ConclusionsThere is a paucity of high quality evidence for CVAR monitoring and its associations with outcome measures in post‐cardiac surgical patients, highlighting the need for future studies.
The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon
Authors: Fontana Luigi , Mitchell Sharon E. , Wang Boshi , Tosti Valeria , van Vliet Thijmen , Veronese Nicola , Bertozzi Beatrice , Early Dayna S. , Maissan Parcival , Speakman John R. , Demaria Marco 
Published: March 2018

SummaryCalorie restriction (CR) is an effective strategy to delay the onset and progression of aging phenotypes in a variety of organisms. Several molecular players are involved in the anti‐aging effects of CR, but mechanisms of regulation are poorly understood. Cellular senescence—a cellular state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate with age and promote a number of age‐related pathologies. Whether environmental conditions such as diet affect the accumulation of cellular senescence with age is still unclear. Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice under CR. Moreover, we demonstrate that such senescence markers are not induced in the colon of middle‐age human volunteers under CR in comparison with age‐matched volunteers consuming normal Western diets. Our data support the idea that the improvement in health span observed in different organisms under CR might be partly due to a reduction in the number of senescent cells.
Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast
Authors: Campos Sergio E. , Avelar‐Rivas J. Abraham , Garay Erika , Juárez‐Reyes Alejandro , DeLuna Alexander 
Published: March 2018

SummaryDietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and γ‐aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross‐talks in aging cells.
Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism
Authors: Guan Ying‐Jie , Li Jing , Yang Xu , Du Shaohua , Ding Jing , Gao Yun , Zhang Ying , Yang Kun , Chen Qian 
Published: March 2018

SummaryPrimary osteoarthritis (OA) is associated with aging, while post‐traumatic OA (PTOA) is associated with mechanical injury and inflammation. It is not clear whether the two types of osteoarthritis share common mechanisms. We found that miR‐146a, a microRNA‐associated with inflammation, is activated by cyclic load in the physiological range but suppressed by mechanical overload in human articular chondrocytes. Furthermore, miR‐146a expression is decreased in the OA lesions of human articular cartilage. To understand the role of miR‐146a in osteoarthritis, we systemically characterized mice in which miR‐146a is either deficient in whole body or overexpressed in chondrogenic cells specifically. miR‐146a‐deficient mice develop early onset of OA characterized by cartilage degeneration, synovitis, and osteophytes. Conversely, miR‐146a chondrogenic overexpressing mice are resistant to aging‐associated OA. Loss of miR‐146a exacerbates articular cartilage degeneration during PTOA, while chondrogenic overexpression of miR‐146a inhibits PTOA. Thus, miR‐146a inhibits both OA and PTOA in mice, suggesting a common protective mechanism initiated by miR‐146a. miR‐146a suppresses IL‐1β of catabolic factors, and we provide evidence that miR‐146a directly inhibits Notch1 expression. Therefore, such inhibition of Notch1 may explain suppression of inflammatory mediators by miR‐146a. Chondrogenic overexpression of miR‐146a or intra‐articular administration of a Notch1 inhibitor alleviates IL‐1β‐induced catabolism and rescues joint degeneration in miR‐146a‐deficient mice, suggesting that miR‐146a is sufficient to protect OA pathogenesis by inhibiting Notch signaling in the joint. Thus, miR‐146a may be used to counter both aging‐associated OA and mechanical injury‐/inflammation‐induced PTOA.
The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence
Authors: Mohrin Mary , Widjaja Andrew , Liu Yufei , Luo Hanzhi , Chen Danica 
Published: March 2018

SummaryThe mitochondrial unfolded protein response (UPRmt), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPRmt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPRmt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking. In this study, we devised three experimental approaches that enable us to monitor quiescent and proliferating hematopoietic stem cells (HSCs) and provided the direct evidence that the UPRmt is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation.
One way or another: predictors of wolf poaching in a legally harvested wolf population
Authors: Suutarinen J. , Kojola I. 
Published: March 2018

AbstractPoaching is a major threat to large predator populations, but the predictors of poaching are poorly mapped in developed countries where illegal killing is motivated by social reasons. Poaching can be common although the species is legally hunted, such as in the case of the wolf (Canis lupus). Our goal was to identify crucial motives of poaching to find possible solutions to the ongoing wolf conflict. We studied predictors of poaching on two spatial scales – countrywide (76 wolves) and territory [30 Global Positioning System (GPS)‐wolves] – during 2001–2016 in Finland. The countrywide factors predicting illegal kill were as follows: (1) lifestage, with adult wolves showing a remarkably high probability of being illegally killed in comparison with juveniles; (2) the number of wolves killed legally in the local scale, that is, licensed wolf hunting at the local scale decreased the likelihood of illegal killing, as did the total number of legally hunted wolves; (3) total legal bag in the whole country; and (4) density of the local human population, that is, low human density increased the probability of illegal kill. For breeding adult GPS‐collared wolves at the territory level, there was a positive relationship between the tendency to cross roads and likelihood of being illegally killed. Our results provided evidence that poaching is a matter of local intolerance toward wolves and that the problem is mainly related to wolf hunting. Legal hunting might decrease poaching, but seems inefficient as a long‐term solution. To maintain a viable wolf population, the poaching risk of breeding adults should be decreased. Predicted poaching probabilities could be used to tackle poaching in a preventive manner by involving both decision makers and local residents in anti‐poaching actions.
Clozapine reduces nicotine self‐administration, blunts reinstatement of nicotine‐seeking but increases responding for food
Authors: Abela Andrew R. , Li Zhaoxia , Lê Anh D. , Fletcher Paul J. 
Published: March 2018

AbstractPeople with schizophrenia display significantly higher rates of smoking than the general population, which may be due to an interaction between nicotine and antipsychotic medication. While the conventional antipsychotic drug haloperidol sometimes increases cigarette smoking in patients with schizophrenia, there is some evidence suggesting that clozapine, an atypical antipsychotic drug, may reduce nicotine use in these patients. However, the effects of antipsychotic drugs like clozapine on aspects of nicotine self‐administration and reinstatement have not been systematically examined. In the current study, we assessed the effect of clozapine on nicotine self‐administration under fixed ratio and progressive ratio schedules of reinforcement, as well as reinstatement of nicotine‐seeking following a period of abstinence. To determine the specificity of its effect on nicotine reward, we also tested the effect of clozapine on responding for food reinforcement under fixed ratio and progressive ratio schedules. For comparison, we also examined the effects of haloperidol, a first‐generation antipsychotic drug, under some of the same behavioral conditions as clozapine. We show that clozapine inhibits nicotine self‐administration and reinstatement of nicotine‐seeking but also increases the amount of effort that rats will exert for food reward. In contrast, haloperidol at a wide range of doses attenuated responding for nicotine and food reward, suggestive of a non‐specific reduction in reinforcer efficacy. These results show the potential utility of clozapine as a smoking cessation treatment for patients with schizophrenia, in addition to its antipsychotic properties.
Denise Kandel's classic work on the gateway sequence of drug acquisition
Authors: Lynskey Michael T. , Agrawal Arpana 
Published: March 2018

AbstractDuring the early 1970s Denise Kandel and her colleagues documented an ‘invariant sequence’ in initiation of drug use: starting with alcohol and tobacco, progressing to cannabis and then to other illicit, or ‘harder’ drugs. This observation, which became known as the ‘gateway sequence’ of drug use, has been influential in policy debates but remains highly contentious, with the area of greatest controversy focusing upon whether cannabis use increases risk causally for initiation of other illicit drugs. While numerous studies have replicated Kandel's initial findings (sequence of onset) and reported that associations between cannabis use and the use of other illicit drugs remain after controlling for potentially confounding factors, the mechanisms underlying these observed associations remain hotly debated. In particular, it is possible that the observed associations are non‐causal but reflect the influence of confounding factors which influence both early‐onset drug use and subsequent progressions. However, research employing a range of techniques to address this issue has been unable to discount the possibility that associations between earlier and subsequent drug use reflect causal processes. This paper reviews Kandel's ongoing contributions to this field, which span 45 years, and discusses both the influence of her work and the controversy that it has aroused.
Attempts to reduce alcohol intake and treatment needs among people with probable alcohol dependence in England: a general population survey
Authors: Dunne Jacklyn , Kimergård Andreas , Brown Jamie , Beard Emma , Buykx Penny , Michie Susan , Drummond Colin 
Published: March 2018

AbstractAimsTo compare the proportion of people in England with probable alcohol dependence [Alcohol Use Disorders Identification Test (AUDIT) score ≥ 20] with those with other drinking patterns (categorized by AUDIT scores) in terms of motivation to reduce drinking and use of alcohol support resources.DesignA combination of random probability and simple quota sampling to conduct monthly cross‐sectional household computer‐assisted interviews between March 2014 and August 2017.SettingThe general population in all nine regions of England.ParticipantsParticipants in the Alcohol Toolkit Study (ATS), a monthly household survey of alcohol consumption among people aged 16 years and over in England (n = 69 826). The mean age was 47 years [standard deviation (SD) = 18.78; 95% confidence interval (CI) = 46.8–47] and 51% (n = 35 560) were female.Measurementsχ2 tests were used to investigate associations with demographic variables, motivation to quit drinking, attempts to quit drinking, general practitioner (GP) engagement and types of support accessed in the last 12 months across AUDIT risk zones.FindingsA total of 0.6% were classified as people with probable alcohol dependence (95% CI = 0.5–0.7). Motivation to quit (χ2 = 1692.27, P < 0.001), current attempts (χ2 = 473.94, P < 0.001) and past‐year attempts (χ2 = 593.67, P < 0.001) differed by AUDIT risk zone. People with probable dependence were more likely than other ATS participants to have a past‐year attempt to cut down or quit (51.8%) and have received a specialist referral from their GP about drinking (13.7%), and less likely to report no motivation to reduce their drinking (26.2%). Those with probable dependence had higher use of self‐help books and mobile applications (apps) than other ATS participants; however, 27.7% did not access any resources during their most recent attempt to cut down.ConclusionsAdults in England with probable alcohol dependence, measured through the Alcohol Use Disorders Identification Test, demonstrate higher motivation to quit drinking and greater use of both specialist treatment and self‐driven support compared with those in other Alcohol Use Disorders Identification Test zones, but most do not access treatment resources to support their attempts.
Keeping secrets: Leslie E. Keeley, the gold cure and the 19th‐century neuroscience of addiction
Authors: Hickman Timothy A. 
Published: March 2018

AbstractBackground and AimsDr Leslie E. Keeley was perhaps the world's most famous addiction cure doctor at the turn of the 20th century, but mainstream medicine dismissed him as a quack because he dispensed a secret cure. This paper aims to describe Keeley's now largely forgotten story and to draw attention to the role of contextual issues in the acceptance or rejection of any theory of addiction, particularly the neuroscientific theories of the early 21st century.MethodsThis study is a qualitative assessment and contextualization of historical documents. Its main sources are archival and are, for the most part, unknown to historians. The paper also offers intellectual and historical context that is drawn from leading historical and sociological analyses.ResultsKeeley's addiction cure was dismissed as quackery because it failed to meet the changing standards of late 19th‐century professional medicine. This begs us to consider contextual issues in any assertion of the viability of addiction therapeutics, in the present as well the past.ConclusionsKeeley's near erasure from the historical record was a consequence of a broader, late 19th‐century medical power struggle that took precedence over the testimony of tens of thousands of satisfied patients who claimed that Keeley's cure worked. Context matters in the assessment of the viability of theories of addiction from the past, but also from the present. Historians and social scientists are well placed to make those assessments.