bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quasi-experimental evaluation of Kenya’s pictorial health warnings versus Zambia’s single text-only warning: findings from the International Tobacco Control (ITC) Project
Authors: Kaai Susan Cherop , Sansone Genevieve , Meng Gang , Ong’ang’o Jane Rahedi , Goma Fastone , Ikamari Lawrence , Quah Anne C K , Fong Geoffrey T 
Published: June 2021

BackgroundPopulation studies in mostly high-income countries have shown that pictorial health warnings (PHWs) are much more effective than text-only warnings. This is the first quasi-experimental evaluation of the introduction of PHWs in Africa, comparing the change from text-only to PHWs in Kenya to the unchanged text-only health warning in Zambia.MethodsData were from International Tobacco Control (ITC) Surveys in Kenya (n=1495), and Zambia (n=1628), cohort surveys of nationally representative samples of adult smokers in each country. The ITC Kenya Survey was conducted in 2012 and 2018 (2 years after the 2016 introduction of three PHWs). The ITC Zambia Survey was conducted in 2012 and 2014 with no change to the single text-only warning. Validated indicators of health warning effectiveness (HWIs) (salience: noticing, reading; cognitive reactions: thinking about health risks, thinking about quitting; and behavioural reactions: avoiding warnings; forgoing a cigarette because of the warnings), and a summary measure—the Labels Impact Index (LII)—measured changes in warning impact between the two countries.ResultsPHWs implemented in Kenya led to a significant increase in all HWIs and the LII, compared with the text-only warning in Zambia. The failure to implement PHWs in Zambia led to a substantial missed opportunity to increase warning effectiveness (eg, an estimated additional 168 392 smokers in Zambia would have noticed the warnings).ConclusionsThe introduction of PHWs in Kenya substantially increased the effectiveness of warnings. These results provide strong empirical support for 34 African countries that still have text-only warnings, of which 31 are Parties of the Framework Convention on Tobacco Control and are thus obligated to implement PHWs.
Analysis of a bistable climate toy model with physics-based machine learning methods
Authors: Gelbrecht Maximilian , Lucarini Valerio , Boers Niklas , Kurths Jürgen 
Published: June 2021

AbstractWe propose a comprehensive framework able to address both the predictability of the first and of the second kind for high-dimensional chaotic models. For this purpose, we analyse the properties of a newly introduced multistable climate toy model constructed by coupling the Lorenz ’96 model with a zero-dimensional energy balance model. First, the attractors of the system are identified with Monte Carlo Basin Bifurcation Analysis. Additionally, we are able to detect the Melancholia state separating the two attractors. Then, Neural Ordinary Differential Equations are applied to predict the future state of the system in both of the identified attractors.
Multiple Roles of IL6 in Hepatic Injury, Steatosis, and Senescence Aggregate to Suppress Tumorigenesis
Authors: Shriki Anat , Lanton Tali , Sonnenblick Amir , Levkovitch-Siany Orr , Eidelshtein Dana , Abramovitch Rinat , Rosenberg Nofar , Pappo Orit , Elgavish Sharona , Nevo Yuval , Safadi Rifaat , Peled Amnon , Rose-John Stefan , Galun Eithan , Axelrod Jonathan H. 
Published: June 2021

AbstractHepatocellular carcinoma (HCC) typically develops on a background of chronic hepatitis for which the proinflammatory cytokine IL6 is conventionally considered a crucial driving factor. Paradoxically, IL6 also acts as a hepatoprotective factor in chronic liver injury. Here we used the multidrug-resistant gene 2 knockout (Mdr2−/−) mouse model to elucidate potential roles of IL6 in chronic hepatitis–associated liver cancer. Long-term analysis of three separate IL6/Stat3 signaling–deficient Mdr2−/− strains revealed aggravated liver injury with increased dysplastic nodule formation and significantly accelerated tumorigenesis in all strains. Tumorigenesis in the IL6/Stat3-perturbed models was strongly associated with enhanced macrophage accumulation and hepatosteatosis, phenotypes of nonalcoholic steatohepatitis (NASH), as well as with significant reductions in senescence and the senescence-associated secretory phenotype (SASP) accompanied by increased hepatocyte proliferation. These findings reveal a crucial suppressive role for IL6/Stat3 signaling in chronic hepatitis–associated hepatocarcinogenesis by impeding protumorigenic NASH-associated phenotypes and by reinforcing the antitumorigenic effects of the SASP.Significance:These findings describe a context-dependent role of IL6 signaling in hepatocarcinogenesis and predict that increased IL6-neutralizing sgp130 levels in some patients with NASH may herald early HCC development.See related commentary by Huynh and Ernst, p. 4671
Subgroup Analyses in Oncology Trials: Regulatory Considerations and Case Examples
Authors: Amatya Anup K. , Fiero Mallorie H. , Bloomquist Erik W. , Sinha Arup K. , Lemery Steven J. , Singh Harpreet , Ibrahim Amna , Donoghue Martha , Fashoyin-Aje Lola A. , de Claro R. Angelo , Gormley Nicole J. , Amiri-Kordestani Laleh , Sridhara Rajeshwari , Theoret Marc R. , Kluetz Paul G. , Pazdur Richard , Beaver Julia A. , Tang Shenghui 
Published: June 2021

Abstract
Subgroup analyses are assessments of treatment effects based on certain patient characteristics out of the total study population and are important for interpretation of pivotal oncology trials. However, appropriate use of subgroup analyses results for regulatory decision-making and product labeling is challenging. Typically, drugs approved by the FDA are indicated for use in the total patient population studied; however, there are examples of restriction to a subgroup of patients despite positive study results in the entire study population and also extension of an indication to the entire study population despite positive results appearing primarily in one or more subgroups. In this article, we summarize key issues related to subgroup analyses in the benefit–risk assessment of cancer drugs and provide case examples to illustrate approaches that the FDA Oncology Center of Excellence has taken when considering the appropriate patient population for cancer drug approval. In general, if a subgroup is of interest, the subgroup analysis should be hypothesis-driven and have adequate sample size to demonstrate evidence of a treatment effect. In addition to statistical efficacy considerations, the decision on what subgroups to include in labeling relies on the pathophysiology of the disease, mechanistic justification, safety data, and external information available. The oncology drug review takes the totality of the data into consideration during the decision-making process to ensure the indication granted and product labeling appropriately reflect the scientific evidence to support patient population for whom the drug is safe and effective.
Clinical and Functional Characterization of AtypicalKRAS/NRASMutations in Metastatic Colorectal Cancer
Authors: Loree Jonathan M. , Wang Yucai , Syed Muddassir A. , Sorokin Alexey V. , Coker Oluwadara , Xiu Joanne , Weinberg Benjamin A. , Vanderwalde Ari M. , Tesfaye Anteneh , Raymond Victoria M. , Miron Benjamin , Tarcic Gabi , Zelichov Ori , Broaddus Russell R. , Ng Patrick Kwok Shing , Jeong Kang Jin , Tsang Yiu Huen , Mills Gordon B. , Overman Michael J. , Grothey Axel , Marshall John L. , Kopetz Scott 
Published: June 2021

AbstractPurpose:Mutations in KRAS/NRAS (RAS) predict lack of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). However, it is unclear if all RAS mutations have similar impact, and atypical mutations beyond those in standard guidelines exist.Experimental Design:We reviewed 7 tissue and 1 cell-free DNA cohorts of 9,485 patients to characterize atypical RAS variants. Using an in vitro cell-based assay (functional annotation for cancer treatment), Ba/F3 transformation, and in vivo xenograft models of transduced isogenic clones, we assessed signaling changes across mutations.Results:KRAS exon 2, extended RAS, and atypical RAS mutations were noted in 37.8%, 9.5%, and 1.2% of patients, respectively. Among atypical variants, KRAS L19F, Q22K, and D33E occurred at prevalence ≥0.1%, whereas no NRAS codon 117/146 and only one NRAS codon 59 mutation was noted. Atypical RAS mutations had worse overall survival than RAS/BRAF wild-type mCRC (HR, 2.90; 95% confidence interval, 1.24–6.80; P = 0.014). We functionally characterized 114 variants with the FACT assay. All KRAS exon 2 and extended RAS mutations appeared activating. Of 57 atypical RAS variants characterized, 18 (31.6%) had signaling below wild-type, 23 (40.4%) had signaling between wild-type and activating control, and 16 (28.1%) were hyperactive beyond the activating control. Ba/F3 transformation (17/18 variants) and xenograft model (7/8 variants) validation was highly concordant with FACT results, and activating atypical variants were those that occurred at highest prevalence in clinical cohorts.Conclusions:We provide best available evidence to guide treatment when atypical RAS variants are identified. KRAS L19F, Q22K, D33E, and T50I are more prevalent than many guideline-included RAS variants and functionally relevant.
As Legislações Brasileiras São Instrumentos que Garantem a Autoestima do Idoso?
Authors: Feitosa Elza Alves 
Published: June 2021

Este artigo tem por objetivo estimular a reflexão sobre o processo de envelhecimento e as políticas públicas que visam proteger a população idosa no Brasil. Menciona as Assembléias Mundiais sobre o Envelhecimento, realizadas em Viena e Madri, nos anos 1982 e 2002, as quais chamaram a atenção dos países quanto à necessidade de proteger os direitos das pessoas idosas. No Brasil houve criação de leis de amparo à velhice, mas pouco tem sido feito para viabilizar o exercício dos direitos assegurados. É imprescindível que o Estado desenvolva políticas públicas para garantir uma melhor qualidade de vida para essa parcela da população. A autoestima é um fator que norteia o processo de envelhecimento, ela pode contribuir para a saúde da pessoa idosa e consequentemente poderá determinar a qualidade de vida. As projeções populacionais impõem ações de prevenção e cuidado direcionados às necessidades das pessoas idosas. É necessário reconhecer os seus direitos para que sejam desenvolvidas e garantidas ações políticas específicas e integradas, que reconheçam suas características e especificidades.
Possible impacts of December Laptev sea ice on Indian Ocean Dipole conditions during spring
Authors: Chen Ping , Sun Bo , Wang Huijun , Zhu Baoyan 
Published: June 2021

AbstractThis study investigates the relationship and underlying mechanisms between the Indian Ocean Dipole (IOD) and Arctic sea ice. The results reveal that the preceding December sea ice over the Laptev Sea plays an important role in the formation of positive IOD conditions during April–June (AMJ). In years with positive December Laptev sea ice anomalies, the zonal wavenumber-1 (ZWN1) planetary wave component is stimulated at middle and high latitudes. The high-latitude ZWN1 propagates upward to the stratosphere and downward to the troposphere in December, affects the atmospheric circulation over the North Atlantic, and further leads to a warm sea surface temperature anomaly (SSTA) that persists until the following February. The mid-latitude ZWN1 propagates upward to the stratosphere in January and downward to the troposphere in February, contributing to the positive 200-hPa geopotential height anomaly (GPHA) in the subtropical Atlantic. The ascending anomaly induced by the warm SSTA and the positive 200-hPa GPHA in the subtropical Atlantic in February are favorable for effective Rossby wave source formation and stimulate an atmospheric wave train that forms an anomalous cyclone over the northern Arabian Sea, which contributes to enhanced convection over North India, stimulating an anomalous anticyclone over East India and leading to reduced convection over the northeastern Indian Ocean in March. The reduced convection over the northeastern Indian Ocean may lead to strengthened equatorial easterly winds and further contribute to positive IOD conditions in AMJ. These findings indicate that December Laptev sea ice may contribute to AMJ IOD conditions.
What Matters? Exploring Drivers of Basic and Complex Adjustments to Tornadoes Among College Students
Authors: Huntsman David , Wu Hao-Che , Greer Alex 
Published: June 2021

AbstractScholars have produced several theories and models to explain why individuals adjust to hazards. While findings from these studies are informative, studies have not considered how threat and coping appraisals may have differential effects on varying types of hazard adjustments, or how these findings may generalize to vulnerable populations. This study expands on the Protection Motivation Theory to explore the factors that shape hazard adjustment intentions among college students, a population traditionally defined as vulnerable, in response to tornado risk. An online survey was administered to college students (n=377) at Oklahoma State University, situated in a region that experiences considerable tornado risk. While the correlations between threat appraisal and tornado hazard adjustment intentions are smaller than the correlations between coping appraisal and tornado hazard adjustment intentions, findings suggest that threat appraisals become more important for influencing college students’ adjustment intentions when adjustment activities are complex (e.g., tornado shelter, home insurance), rather than basic (e.g., flashlight, first aid kid). This suggests that while both threat appraisals and coping appraisals are important for complex hazard adjustment intentions, basic hazard adjustment intentions are almost exclusively determined by coping appraisals. These findings have several practical implications for emergency management and provide new avenues for future hazard adjustment studies.
Comparing the Associated Factors on Lifestyle Between Type 2 Diabetic Patients and Healthy People: A Case-Control Study
Authors: Moradi Farideh , Ziapour Arash , Abbas Jaffar , Najafi Sahar , Rezaeian Shahab , Faraji Obeidollah , Moayeri Elham , Soroush Ali 
Published: June 2021

Background the most important way to control diabetes is to follow a preventive lifestyle and if a diabetic individual follows a preventive lifestyle which he or she has accepted. The main objective of the current study is to compare the factors affecting the lifestyle in patients suffering from Type II diabetes and the healthy individuals in Kermanshah City. Methods this study is based on a case-control design where using simple random sampling, 110 patients suffering from type II diabetes are selected as the case group and 111 healthy subjects among the companions of other patients are selected as the control group from the Center for Diabetics in Kermanshah City. The average age of the participants is [Formula: see text]. The questionnaires used for collecting the data included the following: the demographic information questionnaire and the lifestyle questionnaire which covers diet, physical activity, coping with stress, and smoking. Software applications including STSTA14 and SPSS23 were used for performing statistical computations and logistic regression or linear regression tests were used for analyzing the collected data. Results in the subscales of diet, physical activity, spiritual growth, and stress management, there was a significant difference between the diabetic and healthy groups in a wat that the average score for these subscales was higher in the healthy individuals. While the average score for “health responsibility” was higher in the diabetic group compared to the healthy subjects, the difference was not significant ([Formula: see text]). Moreover, there was a significant statistical relationship between the two groups, i.e. the diabetic and healthy groups, and the variables of age, education level, and occupation (P > 0.05). Conclusion healthy lifestyle including proper diet and athletic activity is effective in preventing type II diabetes. Accordingly, implementing policies in the urban transportation system such as providing a special lane for bikers in the cities, increasing the tax for harmful foods, considering subsidies for healthy food products, and self-care of individuals can be effective.
Closed-Loop Versus Conventional Mechanical Ventilation in COVID-19 ARDS
Authors: Wendel Garcia Pedro David , Hofmaenner Daniel Andrea , Brugger Silvio D. , Acevedo Claudio T. , Bartussek Jan , Camen Giovanni , Bader Patrick Raphael , Bruellmann Gregor , Kattner Johannes , Ganter Christoph , Schuepbach Reto Andreas , Buehler Philipp Karl 
Published: June 2021

Background: Lung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes. Method: Prospective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume <8 ml per kg of ideal body weight, dynamic driving pressure <15 cmH2O, peak pressure <30 cmH2O, peripheral oxygen saturation ≥88% and dynamic mechanical power <17 J/min. Results: Forty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001). Conclusion: Among critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.
Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: Outcome and cost–utility analysis
Authors: Zhao Zixuan , Chen Chi , Sun Xueshan , Zhou Duo , Huang Xinwen , Dong Hengjin 
Published: June 2021

Objectives Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit–cost ratio (BCR), cost–utility ratio (CUR) and incremental cost–utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. Methods The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009–2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost–benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. Results Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders ( n = 276), then fatty acid oxidation disorders ( n = 248), followed by organic acidaemias ( n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ –768,428.76/QALY, and the BCR was 6.09. Conclusions NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.
A Kaleckian wealth tax to support a Green New Deal
Authors: Schroeder Susan 
Published: June 2021

Green New Deals are being widely discussed as both a means to confront climate change and to improve aspects of social well-being. An important facet of the discussion is how they should be financed. The negative impacts of Covid-19 on national budgets and sovereign debt question whether the implementation of Green New Deals is feasible if austerity needs to be introduced to achieve sustainability. This article assesses whether a wealth tax based upon the work of Michal Kalecki could help avoid austerity measures and facilitate the introduction of Green New Deals. While wealth taxes have traditionally been defined on net worth or assets to reduce wealth inequality, the formulation is meant to be equitable by applying to gross wealth or assets. Estimates are calculated for the United States and turn out to be quite modest. The approach not only generates revenue to cover expected net interest outlays on national debt, but additional revenue to pay down portions of it and/or support green initiatives, such as Biden’s de-carbonisation policy. The article concludes with a discussion of challenges for the tax’s effectiveness. JEL Codes: H2, H3, B2, B3