bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical modeling of fluvial strath-terrace formation in response to oscillating climate
Authors: Hancock Gregory S. , Anderson Robert S. 
Published: July 2020

AbstractMany river systems in western North America retain a fluvial strath-terrace rec ord of discontinuous downcutting into bedrock through the Quaternary. Their importance lies in their use to interpret climatic events in the headwaters and to determine long-term incision rates. Terrace formation has been ascribed to changes in sediment supply and/or water discharge produced by late Quaternary climatic fluctuations. We use a one-dimensional channel- evolution model to explore whether temporal variations in sediment and water discharge can generate terrace sequences. The model includes sediment transport, vertical bedrock erosion limited by alluvial cover, and lateral valley-wall erosion. We set limits on our modeling by using data collected from the terraced Wind River basin. Two types of experiments were performed: constant- period sinusoidal input histories and variable-period inputs scaled by the marine δ18O rec ord. Our simulations indicate that strath-terrace formation requires input variability that produces a changing ratio of vertical to lateral erosion rates. Straths are cut when the channel floor is protected from erosion by sediment and are abandoned—and terraces formed—when incision can resume following sediment-cover thinning. High sediment supply promotes wide valley floors that are abandoned as sediment supply decreases. In contrast, wide valleys are promoted by low effective water discharge and are abandoned as discharge increases. Widening of the valley floors that become terraces occurs over many thousands of years. The transition from valley widening to downcutting and terrace creation occurs in response to subtle input changes affecting local divergence of sediment-transport capacity. Formation of terraces lags by several thousand years the input changes that cause their formation.Our results suggest that use of terrace ages to set limits on the timing of a specific event must be done with the knowledge that the system can take thousands of years to respond to a perturbation. The incision rate calculated in the field from the lowest terrace in these systems will likely be higher than the rate calculated by using older terraces, because the most recent fluvial response in the field is commonly downcutting associated with declining sediment input since the Last Glacial Maximum. This apparent increase in incision rates is observed in many river systems and should not necessarily be interpreted as a response to an increase in rock-uplift rate.
Familiarity with the clinical environment, achieved by priming, improves time to antibiotic administration in a simulated paediatric sepsis scenario: a randomised control trial
Authors: McNaughten Ben , Storey Lesley , Corkin Doris , Cardwell Pauline , Thompson Andrew , Bourke Thomas , O'Donoghue Dara 
Published: July 2020

AimThe early administration of antibiotics in sepsis reduces mortality and improves outcomes. This randomised control trial evaluated the effect of environmental priming (EP) on healthcare student performance in a simulated paediatric sepsis scenario.MethodsMedical and nursing students were randomised into primed and unprimed groups. Primed groups received both direct and virtual priming. Each group completed a standardised simulated sepsis scenario. Time to achieve five key clinical interventions was recorded. Mini focus groups were conducted to explore perceptions of EP.ResultsThere were 26 primed and 26 unprimed groups. The primed students were quicker to complete all five interventions and statistically significantly quicker to achieving intravenous (IV) access (median 350 s vs 373 s, p=0.02), administering IV antibiotics (median 648 s vs 760 s, p=0.045) and seeking senior help (median 703 s vs 780 s, p=0.02). Primed students did not feel that they had gained any specific advantage from being primed.ConclusionsEP can improve clinical performance. Implications for practice include incorporating EP of key clinical areas into local induction, standardisation of resuscitation areas and regular use of in situ simulation.
Liver stiffness by transient elastography accompanies illness severity in COVID-19
Authors: Effenberger Maria , Grander Christoph , Fritsche Gernot , Bellmann-Weiler Rosa , Hartig Frank , Wildner Sophie , Seiwald Stefanie , Adolph Timon Erik , Zoller Heinz , Weiss Gunter , Tilg Herbert 
Published: July 2020

ObjectiveSevere liver damage is associated with worse outcome in COVID-19. Our aim was to explore the degree of liver damage, liver stiffness (LS) and severity of illness in patients with COVID-19.DesignWe investigated 32 patients with COVID-19 admitted to the University Hospital of Innsbruck in a prospective cross-sectional study. We performed laboratory testing, liver and spleen sonography and elastography to measure organ stiffness.Results12 patients (38%) showed elevated aminotransferases and gamma-glutamyltransferase levels. LS was positively correlated with elevated aminotransferase levels in patients with COVID-19 compared with those without elevated enzymes. Even mild liver damage raised LS significantly in COVID-19 as it was in patients with gastrointestinal symptoms. Furthermore, higher LS measurements were significantly associated with illness severity like pneumonia, need for mechanical ventilation, and even death.ConclusionTransient elastography is a useful and non-invasive tool to assess onset and severity of acute liver injury in patients with COVID-19 patients. Increased LS seems to be predictive for a more severe and complicated course of disease.
Study protocol of the Health4Life initiative: a cluster randomised controlled trial of an eHealth school-based program targeting multiple lifestyle risk behaviours among young Australians
Authors: Teesson Maree , Champion Katrina E , Newton Nicola C , Kay-Lambkin Frances , Chapman Cath , Thornton Louise , Slade Tim , Sunderland Matthew , Mills Katherine , Gardner Lauren A , Parmenter Belinda , Lubans David R , Hides Leanne , McBride Nyanda , Allsop Steve , Spring Bonnie J , Smout Scarlett , Osman Bridie 
Published: July 2020

IntroductionLifestyle risk behaviours, including alcohol use, smoking, poor diet, physical inactivity, poor sleep (duration and/or quality) and sedentary recreational screen time (‘the Big 6’), are strong determinants of chronic disease. These behaviours often emerge during adolescence and co-occur. School-based interventions have the potential to address risk factors prior to the onset of disease, yet few eHealth school-based interventions target multiple behaviours concurrently. This paper describes the protocol of the Health4Life Initiative, an eHealth school-based intervention that concurrently addresses the Big 6 risk behaviours among secondary school students.Methods and analysisA multisite cluster randomised controlled trial will be conducted among year 7 students (11–13 years old) from 72 Australian schools. Stratified block randomisation will be used to assign schools to either the Health4Life intervention or an active control (health education as usual). Health4Life consists of (1) six web-based cartoon modules and accompanying activities delivered during health education (once per week for 6 weeks), and a smartphone application (universal prevention), and (2) additional app content, for students engaging in two or more risk behaviours when they are in years 8 and 9 (selective prevention). Students will complete online self-report questionnaires at baseline, post intervention, and 12, 24 and 36 months after baseline. Primary outcomes are consumption of sugar-sweetened beverages, moderate-to-vigorous physical activity, sleep duration, sedentary recreational screen time and uptake of alcohol and tobacco use.Ethics and disseminationThis study has been approved by the University of Sydney (2018/882), NSW Department of Education (SERAP no. 2019006), University of Queensland (2019000037), Curtin University (HRE2019-0083) and relevant Catholic school committees. Results will be presented to schools and findings disseminated via peer-reviewed journals and scientific conferences. This will be the first evaluation of an eHealth intervention, spanning both universal and selective prevention, to simultaneously target six key lifestyle risk factors among adolescents.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000431123), 18 March 2019.
Women’s experiences of the renewed National Cervical Screening Program in Australia 12 months following implementation: a qualitative study
Authors: Dodd Rachael H , Mac Olivia A , McCaffery Kirsten J 
Published: July 2020

ObjectiveTo explore women’s experiences of the renewed National Cervical Screening Program in Australia from the perspective of women who have received different human papillomavirus (HPV) test results. Women aged 25 to 74 are now screened every 5 years with primary HPV screening.DesignQualitative interview study.SettingAustralia.ParticipantsWomen in Australia aged 25 to 74 who reported participating in cervical screening since December 2017, purposively sampled by test result (HPV positive, HPV negative and HPV status unknown).Methods26 interviews with women aged 25 to 74 were conducted and analysed thematically.ResultsThree main themes emerged: knowledge and attitudes about the programme changes, information dissemination, the meaning and responses to test results and the new cervical screening test (CST). Some women showed little awareness of the changes, but others understood that HPV is detected earlier than abnormal cells. Some expressed positive attitudes towards the CST and were not anxious about less frequent screening. Most women envisaged the changes would have minimal impact on their screening behaviour. Women mainly wanted more information about the changes and the possible results from the new CST. Overall women could recall their HPV results and understand the implications for future cervical screening. Anxiety about being at ‘increased risk’ was more apparent in women who were HPV positive without history of abnormal results.ConclusionsWomen show some understanding of HPV and the new CST, but more written and public communication about the changes and possible results are warranted. Efforts are needed to ensure that women who are HPV positive without history of abnormal results receive the information needed to alleviate anxiety.
Nutrition and physical activity professional education in gastrointestinal oncology: a national multidisciplinary survey
Authors: Hilmi Marc , Pellat Anna , Benoit Olivier , Foucaut Aude-Marie , Mino Jean-Christophe , Kauffmann Agnes , Rochet Fanny , Heuze Emmanuel , Pudlarz Thomas , Naoun Natacha , Garcia-Larnicol Marie-Line , Delpeut Christine , Peschaud Frederique , Neuzillet Cindy 
Published: July 2020

ObjectivesSarcopenia, present in more than 50% of digestive oncology patients, has a negative impact on clinical outcomes. Nutrition and adapted physical activity are two major interventions for the management of sarcopenia. However, young hepato-gastroenterologists, oncologists and surgeons in France have limited awareness on these topics. We aimed to evaluate the need for training programmes of physicians (residents and senior doctors) involved in digestive oncology on nutrition and adapted physical activity.MethodsA 42-question survey was developed, by a working group of clinicians, dieticians and adapted physical activity teachers, to assess five areas related to demographics of respondents, nutrition practices, nutrition training, adapted physical activity practices and adapted physical activity training. The national survey was undertaken between April and July of 2019.Results230 physicians participated in the survey; 34% were hepato-gastroenterologists, 31% were oncologists, 23% were surgeons and 40% were residents. Sixty-one per cent of participants had received training in nutrition and only 21% in adapted physical activity. Ninety per cent of the physicians expressed their desire for more effective training on these two topics. Disparities in clinical practices were observed between hepato-gastroenterologists, oncologists and surgeons.ConclusionsMore initial and continuing training on nutrition and adapted physical activity is needed for French physicians in the current digestive oncology clinical practice.
Cardiovascular disease in homeless versus housed individuals: a systematic review of observational and interventional studies
Authors: Al-Shakarchi Nader James , Evans Hannah , Luchenski Serena A , Story Alistair , Banerjee Amitava 
Published: July 2020

ObjectivesTo identify: (i) risk of cardiovascular disease (CVD) in homeless versus housed individuals and (ii) interventions for CVD in homeless populations.MethodsWe conducted a systematic literature review in EMBASE until December 2018 using a search strategy for observational and interventional studies without restriction regarding languages or countries. Meta-analyses were conducted, where appropriate and possible. Outcome measures were all-cause and CVD mortality, and morbidity.ResultsOur search identified 17 articles (6 case-control, 11 cohort) concerning risk of CVD and none regarding specific interventions. Nine were included to perform a meta-analysis. The majority (13/17, 76.4%) were high quality and all were based in Europe or North America, including 765 459 individuals, of whom 32 721 were homeless. 12/17 studies were pre-2011. Homeless individuals were more likely to have CVD than non-homeless individuals (pooled OR 2.96; 95% CI 2.80 to 3.13; p<0.0001; heterogeneity p<0.0001; I2=99.1%) and had increased CVD mortality (age-standardised mortality ratio range: 2.6–6.4). Compared with non-homeless individuals, hypertension was more likely in homeless people (pooled OR 1.38–1.75, p=0.0070; heterogeneity p=0.935; I2=0.0%).ConclusionsHomeless people have an approximately three times greater risk of CVD and an increased CVD mortality. However, there are no studies of specific pathways/interventions for CVD in this population. Future research should consider design and evaluation of tailored interventions or integrating CVD into existing interventions.
Patterns of gun owner beliefs about firearm risk in relation to firearm storage: a latent class analysis using the 2019 National Firearms Survey
Authors: Salhi Carmel , Azrael Deborah , Miller Matthew 
Published: July 2020

BackgroundResearch on gun owners’ risk-related beliefs has focused on how gun owners answer discrete questions about firearm risk. The current study is the first to use latent class analysis (LCA) to: (A) identify groups of gun owners who share patterns of beliefs about firearm-related risk and (B) examine whether class membership predicts household firearm storage.MethodsWe conducted LCA using the 2019 National Firearms Survey, a nationally representative survey of US adult gun-owners (n=2950). The LCA assigned gun owners to classes based on responses to four questions about firearm-related risk. Identified classes were included in logistic regression models predicting firearm storage, along with characteristics linked to storage in past research.ResultsThree classes emerged: (1) owners who believe that guns unconditionally make the home safer and should generally be readily accessible (47%); (2) owners who believe that whether guns make homes safer or less safe depends on context (34%); (3) owners who believe that guns do not pose a risk if stored safely (19%). In adjusted models, compared with owners in class 1, those in classes 2 and 3 were less likely to store guns loaded and unlocked (class 2: OR 0.30, 95% CI 0.23 to 0.39; class 3: OR 0.23, 95% CI 0.16 to 0.32).ConclusionOur LCA is a first step towards better understanding variation in patterns of beliefs among gun owners regarding the risks and benefits of firearms. Our results suggest that messaging aimed at promoting safer firearms storage might benefit from the empirically derived typologies we identify.
Leveraging naturally occurring variation in financial stress to examine associations with inflammatory burden among older adults
Authors: Samuel Laura , Szanton Sarah L , Fedarko Neal S , Simonsick Eleanor M 
Published: July 2020

BackgroundFinancial strain is associated with earlier disability and mortality, but causal links are underexplored, partly because it is unethical to randomise people to financial stress. This study leverages naturally occurring random variation in days since monthly Social Security payment arrival among older adults to test associations with inflammatory biomarkers.MethodsBiomarker data, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and C reactive protein (CRP), was collected from 2155 non-working healthy adults aged 70–79 years, participating in the Health, Aging and Body Composition Study. Days since payment arrival was independent of all demographic, socioeconomic or health characteristics measured in this study. Restricted cubic spline models estimated associations separately for each week of the month, stratified by financial strain status (interaction term p value for TNF-α model <0.05).ResultsAmong financially strained older adults, more days since payment arrival was associated with higher TNF-α levels during the first week of the month (coefficient=0.102). Associations with IL-6 and CRP differed depending on the degree of financial strain (interaction term p values <0.05). Those with low, but not high, strain had lower levels of IL-6 (coefficient=−0.152) and CRP (coefficient=−0.179) during the first week.ConclusionsDays since monthly payments were associated with inflammatory cytokines among older adults who have difficulty making ends meet financially and associations depended on financial strain severity, suggesting that results are attributable to monthly variation in financial stress. Future research should examine whether more frequent Social Security disbursement would modify financial strain and inflammatory biomarkers.
RAD51AP1 Deficiency Reduces Tumor Growth by Targeting Stem Cell Self-Renewal
Authors: Bridges Allison E. , Ramachandran Sabarish , Pathania Rajneesh , Parwal Utkarsh , Lester Adrienne , Rajpurohit Pragya , Morera Daley S. , Patel Nikhil , Singh Nagendra , Korkaya Hasan , Manicassamy Santhakumar , Prasad Puttur D. , Lokeshwar Vinata B. , Lokeshwar Bal L. , Ganapathy Vadivel , Thangaraju Muthusamy 
Published: July 2020

Abstract

RAD51-associated protein 1 (RAD51AP1) plays an integral role in homologous recombination by activating RAD51 recombinase. Homologous recombination is essential for preserving genome integrity and RAD51AP1 is critical for D-loop formation, a key step in homologous recombination. Although RAD51AP1 is involved in maintaining genomic stability, recent studies have shown that RAD51AP1 expression is significantly upregulated in human cancers. However, the functional role of RAD51AP1 in tumor growth and the underlying molecular mechanism(s) by which RAD51AP1 regulates tumorigenesis have not been fully understood. Here, we use Rad51ap1-knockout mice in genetically engineered mouse models of breast cancer to unravel the role of RAD51AP1 in tumor growth and metastasis. RAD51AP1 gene transcript was increased in both luminal estrogen receptor–positive breast cancer and basal triple-negative breast cancer, which is associated with poor prognosis. Conversely, knockdown of RAD51AP1 (RADP51AP1 KD) in breast cancer cell lines reduced tumor growth. Rad51ap1-deficient mice were protected from oncogene-driven spontaneous mouse mammary tumor growth and associated lung metastasis. In vivo, limiting dilution studies provided evidence that Rad51ap1 plays a critical role in breast cancer stem cell (BCSC) self-renewal. RAD51AP1 KD improved chemotherapy and radiotherapy response by inhibiting BCSC self-renewal and associated pluripotency. Overall, our study provides genetic and biochemical evidences that RAD51AP1 is critical for tumor growth and metastasis by increasing BCSC self-renewal and may serve as a novel target for chemotherapy- and radiotherapy-resistant breast cancer.

Significance:
This study provides in vivo evidence that RAD51AP1 plays a critical role in breast cancer growth and metastasis by regulating breast cancer stem cell self-renewal.
The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling
Authors: Jackson Dakota N. , Alula Kibrom M. , Delgado-Deida Yaritza , Tabti Redouane , Turner Kevin , Wang Xuan , Venuprasad K. , Souza Rhonda F. , Désaubry Laurent , Theiss Arianne L. 
Published: July 2020

Abstract

Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors of the Wnt/β-catenin pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative of natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, but has not been previously tested in cell or preclinical models of intestinal tumorigenesis. In vitro studies suggest that flavaglines target prohibitin 1 (PHB1) as a ligand, but this has not been established in the intestine. PHB1 is a highly conserved protein with diverse functions that depend on its posttranslational modifications and subcellular localization. Here, we demonstrate that FL3 combats intestinal tumorigenesis in the azoxymethane-dextran sodium sulfate and ApcMin/+ mouse models and in human colorectal cancer tumor organoids (tumoroids) by inhibiting Wnt/β-catenin signaling via induction of Axin1 expression. FL3 exhibited no change in cell viability in normal intestinal epithelial cells or human matched-normal colonoids. FL3 response was diminished in colorectal cancer cell lines and human colorectal cancer tumoroids harboring a mutation at S45 of β-catenin. PHB1 deficiency in mice or in human colorectal cancer tumoroids abolished FL3-induced expression of Axin1 and drove tumoroid death. In colorectal cancer cells, FL3 treatment blocked phosphorylation of PHB1 at Thr258, resulting in its nuclear translocation and binding to the Axin1 promoter. These results suggest that FL3 inhibits Wnt/β-catenin signaling via PHB1-dependent activation of Axin1. FL3, therefore, represents a novel compound that combats Wnt pathway–dependent cancers, such as colorectal cancer.

Significance:
Targeting of PHB1 by FL3 provides a novel mechanism to combat Wnt-driven cancers, with limited intestinal toxicity.
Progresses Toward Precision Medicine inRET-altered Solid Tumors
Authors: Belli Carmen , Anand Santosh , Gainor Justin F. , Penault-Llorca Frederique , Subbiah Vivek , Drilon Alexander , Andrè Fabrice , Curigliano Giuseppe 
Published: July 2020

AbstractRET (rearranged during transfection) gene encodes a receptor tyrosine kinase essential for many physiologic functions, but RET aberrations are involved in many pathologies. While RET loss-of-function mutations are associated with congenital disorders like Hirschsprung disease and CAKUT, RET gain-of-function mutations and rearrangements are critical drivers of tumor growth and proliferation in many different cancers. RET-altered (RET+) tumors have been hitherto targeted with multikinase inhibitors (MKI) having anti-RET activities, but they inhibit other kinase targets more potently and show limited clinical activities. The lack of target specificity and consequently increased side effects, responsible for dose reduction and drug discontinuation, are critical limitations of MKIs in the clinics. New selective RET inhibitors, selpercatinib and pralsetinib, are showing promising activities, improved response rates, and more favorable toxicity profiles in early clinical trials. This review critically discusses the oncogenic activation of RET and its role in different kinds of tumors, clinical features of RET+ tumors, clinically actionable genetic RET alterations and their diagnosis, and the available data and results of nonselective and selective targeting of RET.