bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-superiority of lumen-apposing metal stents over plastic stents for drainage of walled-off necrosis in a randomised trial
Authors: Bang Ji Young , Navaneethan Udayakumar , Hasan Muhammad K , Sutton Bryce , Hawes Robert , Varadarajulu Shyam 
Published: August 2019

ObjectiveAlthough lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off necrosis (WON), their advantage over plastic stents is unclear. We compared efficacy of LAMS and plastic stents for WON drainage.DesignPatients with WON were randomised to endoscopic ultrasound-guided drainage using LAMS or plastic stents. Primary outcome was comparing total number of procedures to achieve treatment success defined as symptom relief in conjunction with WON resolution on CT at 6 months. Secondary outcomes were treatment success, procedure duration, clinical/stent-related adverse events, readmissions, length of hospital stay (LOS) and costs.Results60 patients underwent LAMS (n=31) or plastic stent (n=29) placement. There was no significant difference in total number of procedures performed (median 2 (range 2–7) LAMS vs 3 (range 2–7) plastic, p=0.192), treatment success, clinical adverse events, readmissions, LOS and overall treatment costs between cohorts. Although procedure duration was shorter (15 vs 40 min, p<0.001), stent-related adverse events (32.3% vs 6.9%, p=0.01) and procedure costs (US$12 155 vs US$6609, p<0.001) were higher with LAMS. Significant stent-related adverse events were observed ≥3 weeks postintervention in LAMS cohort. Interim audit resulted in protocol amendment where CT scan was obtained at 3 weeks postintervention followed by LAMS removal if WON had resolved. After protocol amendment, there was no significant difference in adverse events between cohorts.ConclusionExcept for procedure duration, there was no significant difference in treatment outcomes between LAMS and plastic stents. To minimise adverse events with LAMS, patients should undergo follow-up imaging and stent removal at 3 weeks if WON has resolved.Trial registration numberNCT02685865.
Hazardous children’s products on the Australian and US market 2011–2017: an empirical analysis of child-related product safety recalls
Authors: Niven Catherine M , Mathews Ben , Harrison James E , Vallmuur Kirsten 
Published: August 2019

ObjectiveWhile there is evidence that unsafe children’s products are entering the Australian market, with increasing product safety recalls, no research has examined the nature of recalls or their trends over time. This research analyses Australian and US child-related product safety recall data to better understand the frequency and nature of unsafe children’s products, emerging hazard trends and cross-jurisdictional similarities and differences. Results can inform improved childhood injury prevention policy and regulation strategies in Australia.MethodEmpirical analysis of child-related product safety recalls in Australia and the USA over the period 2011–2017.ResultsCross-jurisdictional comparison revealed similarities in Australia and the USA, with over 80% of recalled products occurring in four industry segments (toys/games, household furniture/furnishings, clothing and sports equipment) and a common leading hazard of choking. Australia and the USA also had a similar number of child-related recalls over the study period (Australia: 652, USA: 668). Disparate trends included a 21% decrease in US child-related recalls over the study period, with most recalled products still complying with mandated safety requirements. In contrast, Australian child-related recalls increased by 88% over the study period, with the majority of recalled products failing to comply with mandated safety requirements. Based on US child-related recall data, the leading cause of injuries was the child falling, the most severe injuries related to furniture/furnishings and the most frequent injuries related to sports equipment.ConclusionAnalysing recall data provides new insights into hazardous children’s products. Cross-jurisdictional comparison of data on recalls highlights disparities and indicates a need for reforms to improve regulation of children’s products in Australia.
Forecasting global road traffic injury mortality for 2030
Authors: Inada Haruhiko , Li Qingfeng , Bachani Abdulgafoor , Hyder Adnan A 
Published: August 2019

ObjectiveTo forecast the number and rate of deaths from road traffic injuries (RTI) in the world in 2030.MethodsThis study was a secondary analysis of annual country-level data of RTI mortality rates for 1990–2017 in the Global Burden of Disease (GBD) 2017 Study, population projection for 2030, gross domestic product (GDP) per capita for 1990–2030 and average years of schooling among people aged 15 years+ for 1990–2030. We developed up to 6884 combinations of forecasting models for each subgroup stratified by country, sex and mode of transport using linear and squared year, GDP per capita and average years of schooling as potential predictors. We conducted a fixed-size, rolling window out-of-sample forecast to choose the best combination for each subgroup. In the validation, we used the data for 1990–2002, 1991–2003 and 1992–2004 (fit periods) to forecast mortality rates in 2015, 2016 and 2017 (test periods), respectively. We applied the selected combination of models to the data for 1990–2017 to forecast the mortality rate in 2030 for each subgroup. To forecast the number of deaths, we multiplied the forecasted mortality rates by the corresponding population projection.ResultsDuring the test periods, the selected combination of models produced the number of deaths that is higher than that estimated in the GBD Study by 5.1% collectively. Our model resulted in 1.225 million deaths and 14.3 deaths per 100 000 population in 2030, which were 1% and 12% less than those for 2017 in the GBD Study, respectively.ConclusionsThe world needs to accelerate its efforts towards achieving the Decade of Action for Road Safety goal and the Sustainable Development Goals target.
Increasing the perceived relevance of cervical screening in older women who do not plan to attend screening
Authors: Marlow Laura A V , Ryan Mairead , Waller Jo 
Published: August 2019

ObjectivesUptake of cervical screening among women aged 50–64 years is declining. Not feeling at risk because of current sexual behaviour is a reason some older women give for not being screened. We hypothesised that explaining the long interval between acquiring human papillomavirus (HPV) and developing cervical cancer would increase the relevance of screening in older women.MethodsWomen aged 50–64 years (n=597) who did not intend to go for screening were recruited through an online panel and randomised to one of three information conditions:cause only(basic information about HPV and cervical cancer),cause with basic timeline(also read a sentence describing the long interval between acquiring HPV and developing cervical cancer) andcause with explicit timeline(read the same as the timeline group alongside an explanation of what this means for older women). Perceived risk of cervical cancer, screening intention strength and understanding of HPV were assessed preinformation and postinformation exposure.ResultsInformation condition was significantly associated with risk perceptions and intention strength postintervention (F(2,593)=6.26, p=0.002 and F(2,593)=4.98, p=0.007 respectively). Women in thecause with explicit timelinecondition were more likely to increase their risk perceptions and intention strength compared withcause only(24% vs 9% and 25% vs 13% for risk perceptions and intention, respectively). In thecause with explicit timelinegroup, women with 4–10 lifetime partners had higher odds of increasing their perceived risk and intention strength postintervention compared with those with 0–1 partners (OR=2.27, 95% CI 1.01 to 5.12 and OR=3.20, 95% CI 1.34 to 7.67, respectively).ConclusionsProviding a clear explanation that decouples women’s perceived cervical cancer risk from their current sexual behaviour has the potential to increase perceived risk of cervical cancer and intentions to be screened among older women. Providing women with a clear cognitive representation of the aetiology of cervical cancer may be one approach to increasing screening uptake.
Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21
Authors: Albadrani Muayad , Seth Ratanesh K. , Sarkar Sutapa , Kimono Diana , Mondal Ayan , Bose Dipro , Porter Dwayne E. , Scott Geoff I. , Brooks Bryan , Raychoudhury Samir , Nagarkatti Mitzi , Nagarkatti Prakash , Jule Yvon , Diehl Anna Mae , Chatterjee Saurabh 
Published: August 2019

Nonalcoholic fatty liver disease (NAFLD) is an emerging global pandemic. Though significant progress has been made in unraveling the pathophysiology of the disease, the role of protein phosphatase 2A (PP2A) and its subsequent inhibition by environmental and genetic factors in NAFLD pathophysiology remains unclear. The present report tests the hypothesis that an exogenous PP2A inhibitor leads to hepatic inflammation and fibrogenesis via an NADPH oxidase 2 (NOX2)-dependent pathway in NAFLD. Results showed that microcystin (MC) administration, a potent PP2A inhibitor found in environmental exposure, led to an exacerbation of NAFLD pathology with increased CD68 immunoreactivity, the release of proinflammatory cytokines, and stellate cell activation, a process that was attenuated in mice that lacked the p47phox gene and miR21 knockout mice. Mechanistically, leptin-primed immortalized Kupffer cells (a mimicked model for an NAFLD condition) treated with apocynin or nitrone spin trap 5,5 dimethyl-1- pyrroline N-oxide (DMPO) had significantly decreased CD68 and decreased miR21 and α-smooth muscle actin levels, suggesting the role of NOX2-dependent reactive oxygen species in miR21-induced Kupffer cell activation and stellate cell pathology. Furthermore, NOX2-dependent peroxynitrite generation was primarily responsible for cellular events observed following MC exposure since incubation with phenylboronic acid attenuated miR21 levels, Kupffer cell activation, and inflammatory cytokine release. Furthermore, blocking of the AKT pathway attenuated PP2A inhibitor-induced NOX2 activation and miR21 upregulation. Taken together, we show that PP2A may have protective roles, and its inhibition exacerbates NAFLD pathology via activating NOX2-dependent peroxynitrite generation, thus increasing miR21-induced pathology. NEW & NOTEWORTHY Protein phosphatase 2A inhibition causes nonalcoholic steatohepatitis (NASH) progression via NADPH oxidase 2. In addition to a novel emchanism of action, we describe a new tool to describe NASH histopathology.
CDK4 Regulates Lysosomal Function and mTORC1 Activation to Promote Cancer Cell Survival
Authors: Martínez-Carreres Laia , Puyal Julien , Leal-Esteban Lucía C. , Orpinell Meritxell , Castillo-Armengol Judit , Giralt Albert , Dergai Oleksandr , Moret Catherine , Barquissau Valentin , Nasrallah Anita , Pabois Angélique , Zhang Lianjun , Romero Pedro , Lopez-Mejia Isabel C. , Fajas Lluis 
Published: August 2019

Abstract

Cyclin-dependent kinase 4 (CDK4) is well-known for its role in regulating the cell cycle, however, its role in cancer metabolism, especially mTOR signaling, is undefined. In this study, we established a connection between CDK4 and lysosomes, an emerging metabolic organelle crucial for mTORC1 activation. On the one hand, CDK4 phosphorylated the tumor suppressor folliculin (FLCN), regulating mTORC1 recruitment to the lysosomal surface in response to amino acids. On the other hand, CDK4 directly regulated lysosomal function and was essential for lysosomal degradation, ultimately regulating mTORC1 activity. Pharmacologic inhibition or genetic inactivation of CDK4, other than retaining FLCN at the lysosomal surface, led to the accumulation of undigested material inside lysosomes, which impaired the autophagic flux and induced cancer cell senescence in vitro and in xenograft models. Importantly, the use of CDK4 inhibitors in therapy is known to cause senescence but not cell death. To overcome this phenomenon and based on our findings, we increased the autophagic flux in cancer cells by using an AMPK activator in combination with a CDK4 inhibitor. The cotreatment induced autophagy (AMPK activation) and impaired lysosomal function (CDK4 inhibition), resulting in cell death and tumor regression. Altogether, we uncovered a previously unknown role for CDK4 in lysosomal biology and propose a novel therapeutic strategy to target cancer cells.

Significance:
These findings uncover a novel function of CDK4 in lysosomal biology, which promotes cancer progression by activating mTORC1; targeting this function offers a new therapeutic strategy for cancer treatment.
eIF4A Inhibitors Suppress Cell-Cycle Feedback Response and Acquired Resistance to CDK4/6 Inhibition in Cancer
Authors: Kong Tim , Xue Yibo , Cencic Regina , Zhu Xianbing , Monast Anie , Fu Zheng , Pilon Virginie , Sangwan Veena , Guiot Marie-Christine , Foulkes William D. , Porco John A. , Park Morag , Pelletier Jerry , Huang Sidong 
Published: August 2019

AbstractCDK4/6 inhibitors are FDA-approved drugs for estrogen receptor–positive (ER+) breast cancer and are being evaluated to treat other tumor types, including KRAS-mutant non–small cell lung cancer (NSCLC). However, their clinical utility is often limited by drug resistance. Here, we sought to better understand the resistant mechanisms and help devise potential strategies to overcome this challenge. We show that treatment with CDK4/6 inhibitors in both ER+ breast cancer and KRAS-mutant NSCLC cells induces feedback upregulation of cyclin D1, CDK4, and cyclin E1, mediating drug resistance. We demonstrate that rocaglates, which preferentially target translation of key cell-cycle regulators, effectively suppress this feedback upregulation induced by CDK4/6 inhibition. Consequently, combination treatment of CDK4/6 inhibitor palbociclib with the eukaryotic initiation factor (eIF) 4A inhibitor, CR-1-31-B, is synergistic in suppressing the growth of these cancer cells in vitro and in vivo. Furthermore, ER+ breast cancer and KRAS-mutant NSCLC cells that acquired resistance to palbociclib after chronic drug exposure are also highly sensitive to this combination treatment strategy. Our findings reveal a novel strategy using eIF4A inhibitors to suppress cell-cycle feedback response and to overcome resistance to CDK4/6 inhibition in cancer.
Refining the Association Between Body Mass Index and Atrial Fibrillation: G‐Formula and Restricted Mean Survival Times
Authors: Conner Sarah C. , Lodi Sara , Lunetta Kathryn L. , Casas Juan P. , Lubitz Steven A. , Ellinor Patrick T. , Anderson Christopher D. , Huang Qiuxi , Coleman Justin , White Wendy B. , Benjamin Emelia J. , Trinquart Ludovic 
Published: August 2019

Background

Previous studies assessing the association between body mass index (
BMI
) and atrial fibrillation (
AF
) did not account for time‐varying covariates, which may be affected by previous
BMI
. We illustrate how the g‐formula can account for time‐varying confounding.

Methods and Results

We included 4392 participants from the Framingham Heart Study who were AF free at ages 45 to 55 years, and followed them for up to 20 years. We estimated hazard ratios (
HR
s) comparing time‐varying nonobese versus obese with Cox models. We used the g‐formula to compare nonobese versus obese and 10% annual decrease in
BMI
(until normal weight is reached) versus natural course. We estimated
HR
s and differences in restricted mean survival times, the mean difference in time alive and
AF
free. We adjusted for sex, age, and time‐varying risk factors. Cox models indicated that nonobese participants had a decreased rate of
AF
versus obese participants (
HR
, 0.83; 95%
CI
, 0.72–0.97). G‐formula analyses comparing everyone had they been nonobese versus obese yielded stronger associations (
HR
, 0.73; 95%
CI
, 0.58–0.91). The restricted mean survival time was 19.22 years had everyone been nonobese and 19.03 years had everyone been obese (difference, 2.25 months; 95%
CI,
−0.66 to 5.16). When assessing a 10% annual decrease in
BMI
, the association was weaker (
HR
0.96; 95%
CI
, 0.86–1.08).

Conclusions

Decreased
BMI
was associated with a lower rate of
AF
after accounting for time‐varying covariates that depend on previous exposure using the g‐formula, which Cox models cannot accommodate. Absolute measures like the restricted mean survival time difference offer context to relative measures of association.
Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment
Authors: Wagenaar Nienke , van den Berk Daphne J.M. , Lemmers Petra M.A. , van der Aa Niek E. , Dudink Jeroen , van Bel Frank , Groenendaal Floris , de Vries Linda S. , Benders Manon J.N.L. , Alderliesten Thomas 
Published: August 2019

Background and Purpose—
In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit.

Methods—

aEEG patterns and regional cerebral oxygen saturation (rScO
2
) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome.

Results—

In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours;
P
<0.05). rScO
2
decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO
2
asymmetry ratio of 4.5% (interquartile range, −4.3% to 5.9%;
P
<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO
2
were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO
2
asymmetry between hemispheres was related with an increased risk for cognitive deficit (<−1 SD) at a median of 24.0 (interquartile range, 18.4–24.4) months of age.

Conclusions—
Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.
Effectiveness and Safety of Rivaroxaban 15 or 20 mg Versus Vitamin K Antagonists in Nonvalvular Atrial Fibrillation
Authors: Blin Patrick , Fauchier Laurent , Dureau-Pournin Caroline , Sacher Frédéric , Dallongeville Jean , Bernard Marie-Agnès , Lassalle Regis , Droz-Perroteau Cécile , Moore Nicholas 
Published: August 2019

Background and Purpose—
We compared the 1-year safety and effectiveness of rivaroxaban 15 mg (R15) or rivaroxaban 20 mg (R20) to vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation.

Methods—
New user cohort study of patients dispensed R15 or R20 versus VKA in 2013 or 2014 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million people). R15 and R20 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high-dimensional propensity score. Hazard ratios (95% CIs) for stroke and systemic embolism, major bleeding, and death were computed using Cox proportional hazards or models by Fine and Gray during exposure.

Results—

In 31 171 matched R20 and VKA, mean age, 71; 62% men; 76% with CHA
2
DS
2
-VASc ≥2; 5% HAS-BLED >3 (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol); incidence rates for stroke and systemic embolism were 1.5% and 1.9% (hazard ratio, 0.79 [0.69–0.90]); major bleeding, 1.5% and 2.2% (0.67 [0.59–0.77]); death, 3.9% and 5.8% (0.67 [0.61–0.73]). In 23 314 matched R15 and VKA patients, mean age, 80; 47% men; 93% with CHA
2
DS
2
-VASc ≥2 and 9% with HAS-BLED >3; incidence rates of stroke and systemic embolism were 2.3% and 2.1% (1.05 [0.92–1.21]); major bleeding, 2.4% and 2.9% (0.84 [0.74–0.96]); death, 9.1% and 10.8% (0.85 [0.79–0.90]). Numbers needed to treat to observe one fewer death (NNT) were 46 for R15 and 61 for R20.

Conclusions—
In real life in France over 2013 to 2015, R15 and R20 were at least as effective and safer than VKA.

Clinical Trial Registration—

URL:
http://www.encepp.eu
. Unique identifier: EUPAS14567.
Potential Predictability of North China Summer Drought
Authors: Zhang Lixia , Zhou Tianjun , Wu Peili , Chen Xiaolong 
Published: August 2019

AbstractAny skillful prediction is of great benefit to North China, a region that is densely populated and greatly impacted by droughts. This paper reports potential predictability of North China summer drought 1 month ahead based on hindcasts for 1961–2005 from the “ENSEMBLES” project. Correlation scores of the standardized precipitation–evapotranspiration index and standardized precipitation index reach 0.49 and 0.39, respectively. The lower-level northwestern Pacific cyclonic circulation anomaly (NWPCCA) and East Asian upper-tropospheric temperature (UTT) cooling are the crucial circulations with regard to summer drought. Two sources of predictability are identified: 1) Pacific–Japan and Silk Road teleconnections forced by well-established eastern Pacific Ocean El Niño sea surface temperature anomalies (SSTA) in summer, when the two key circulations are both well predicted because of a good prediction of enhanced equatorial central Pacific (CP) rainfall and Indian rainfall deficit, and 2) the subtropical atmosphere–ocean coupling associated with CP El Niño developing, when the skill mainly arises from the reasonable prediction of NWPCCA. In observations, the NWPCCA persists from the preceding spring to summer through a wind–evaporation–SST feedback related to the Pacific meridional mode (PMM). In predictions, the persistence of the NWPCCA is mainly forced by the enhanced convection over the subtropical central North Pacific due to the persistence of the PMM-related meridional SSTA gradient over the CP. This predicted SSTA suppresses the equatorial Pacific rainfall, contributing to low prediction skill for the East Asian UTT cooling. This study demonstrates the importance of extratropical signals from the preceding season in North China summer drought prediction.