bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does a complex intervention targeting communities, health facilities and district health managers increase the utilisation of community-based child health services? A before and after study in intervention and comparison areas of Ethiopia
Authors: Berhanu Della , Okwaraji Yemisrach Behailu , Defar Atkure , Bekele Abebe , Lemango Ephrem Tekle , Medhanyie Araya Abrha , Wordofa Muluemebet Abera , Yitayal Mezgebu , W/Gebriel Fitsum , Desta Alem , Gebregizabher Fisseha Ashebir , Daka Dawit Wolde , Hunduma Alemayehu , Beyene Habtamu , Getahun Tigist , Getachew Theodros , Woldemariam Amare Tariku , Wolassa Desta , Persson Lars Åke , Schellenberg Joanna 
Published: September 2020

IntroductionEthiopia successfully reduced mortality in children below 5 years of age during the past few decades, but the utilisation of child health services was still low. Optimising the Health Extension Programme was a 2-year intervention in 26 districts, focusing on community engagement, capacity strengthening of primary care workers and reinforcement of district accountability of child health services. We report the intervention’s effectiveness on care utilisation for common childhood illnesses.MethodsWe included a representative sample of 5773 households with 2874 under-five children at baseline (December 2016 to February 2017) and 10 788 households and 5639 under-five children at endline surveys (December 2018 to February 2019) in intervention and comparison areas. Health facilities were also included. We assessed the effect of the intervention using difference-in-differences analyses.ResultsThere were 31 intervention activities; many were one-off and implemented late. In eight districts, activities were interrupted for 4 months. Care-seeking for any illness in the 2 weeks before the survey for children aged 2–59 months at baseline was 58% (95% CI 47 to 68) in intervention and 49% (95% CI 39 to 60) in comparison areas. At end-line it was 39% (95% CI 32 to 45) in intervention and 34% (95% CI 27 to 41) in comparison areas (difference-in-differences −4 percentage points, adjusted OR 0.49, 95% CI 0.12 to 1.95). The intervention neither had an effect on care-seeking among sick neonates, nor on household participation in community engagement forums, supportive supervision of primary care workers, nor on indicators of district accountability for child health services.ConclusionWe found no evidence to suggest that the intervention increased the utilisation of care for sick children. The lack of effect could partly be attributed to the short implementation period of a complex intervention and implementation interruption. Future funding schemes should take into consideration that complex interventions that include behaviour change may need an extended implementation period.Trial registration numberISRCTN12040912.
Management of children visiting the emergency department during out-of-office hours: an observational study
Authors: Schinkelshoek Gina , Borensztajn Dorine M , Zachariasse Joany M , Maconochie Ian K , Alves Claudio F , Freitas Paulo , Smit Frank J , van der Lei Johan , Steyerberg Ewout W , Greber-Platzer Susanne , Moll Henriëtte A 
Published: September 2020

BackgroundThe aim was to study the characteristics and management of children visiting the emergency department (ED) during out-of-office hours.MethodsWe analysed electronic health record data from 119 204 children visiting one of five EDs in four European countries. Patient characteristics and management (diagnostic tests, treatment, hospital admission and paediatric intensive care unit admission) were compared between children visiting during office hours and evening shifts, night shifts and weekend day shifts. Analyses were corrected for age, gender, Manchester Triage System urgency, abnormal vital signs, presenting problems and hospital.ResultsPatients presenting at night were younger (median (IQR) age: 3.7 (1.4–8.2) years vs 4.8 (1.8–9.9)), more often classified as high urgent (16.3% vs 9.9%) and more often had ≥2 abnormal vital signs (22.8% vs 18.1%) compared with office hours. After correcting for disease severity, laboratory and radiological tests were less likely to be requested (adjusted OR (aOR): 0.82, 95% CI 0.78–0.86 and aOR: 0.64, 95% CI 0.60–0.67, respectively); treatment was more likely to be undertaken (aOR: 1.56, 95% CI 1.49–1.63) and patients were more likely to be admitted to the hospital (aOR: 1.32, 95% CI 1.24–1.41) at night. Patterns in management during out-of-office hours were comparable between the different hospitals, with variability remaining.ConclusionsChildren visiting during the night are relatively more seriously ill, highlighting the need to keep improving emergency care on a 24-hour-a-day basis. Further research is needed to explain the differences in management during the night and how these differences affect patient outcomes.
Clinical trial of carotid artery stenting using dual-layer CASPER stent for carotid endarterectomy in patients at high and normal risk in the Japanese population
Authors: Imamura Hirotoshi , Sakai Nobuyuki , Matsumoto Yasushi , Yamagami Hiroshi , Terada Tomoaki , Fujinaka Toshiyuki , Yoshimura Shinichi , Sugiu Kenji , Ishii Akira , Matsumaru Yuji , Izumi Takashi , Oishi Hidenori , Higashi Toshio , Iihara Koji , Kuwayama Naoya , Ito Yasushi , Nakamura Masato , Hyodo Akio , Ogasawara Kuniaki 
Published: September 2020

Background
The dual-layer nitinol CASPER stent was designed to prevent plaque prolapse into its strut and periprocedural stroke.

Objective
To conduct a clinical trial for government approval of the device in patients at either high or normal risk for carotid endarterectomy (CEA).

Methods
Eligible patients had ≥50% symptomatic stenosis or ≥80% asymptomatic stenosis according to the North American Symptomatic Carotid Endarterectomy Trial methods (peak systolic velocity 130 and 230 cm/s on ultrasonography, respectively). The primary endpoint was the lack of major adverse events (MAEs), defined as death, stroke, and myocardial infarction within 30 days, and ipsilateral stroke within 1 year. The performance goal was set at 90.5%. MAE rates were also compared between the CEA high- and normal-risk groups.

Results
140 carotid artery stenting procedures, including 40% of patients at high risk and 60% at normal risk for CEA, were performed in 13 institutes. MAEs occurred in two cases (one intraprocedural and one postprocedural stroke), and the MAE rate was 1.4%. The non-MAE rate was 98.6% according to Kaplan-Meier analysis, which was superior to the previously set performance goal. The deployment success, target lesion revascularization (TLR), in-stent restenosis, and cerebrovascular event rates were 99.3%, 2.4%, 8.5%, and 7.2%, respectively. The MAE rate in patients with normal CEA risk was 1.2%, which was similar to the high-risk CEA group, with no significant difference due to the small number of MAEs.

Conclusions
The MAE rate following use of the CASPER stent was low (1.4%). The MAE, deployment success, TLR, in-stenosis, and cerebrovascular event rates were similar to those of previous reports.
Differences in the presentation and management of patients with severe aortic stenosis in different European centres
Authors: Lutz Matthias , Messika-Zeitoun David , Rudolph Tanja K , Schulz Eberhard , Thambyrajah Jeetendra , Lloyd Guy , Lauten Alexander , Frey Norbert , Kurucova Jana , Thoenes Martin , Deutsch Cornelia , Bramlage Peter , Steeds Richard Paul 
Published: September 2020

BackgroundAn investigation into differences in the management and treatment of severe aortic stenosis (AS) between Germany, France and the UK may allow benchmarking of the different healthcare systems and identification of levers for improvement.MethodsPatients with a diagnosis of severe AS under management at centres within the IMPULSE and IMPULSE enhanced registries were eligible.ResultsData were collected from 2052 patients (795 Germany; 542 France; 715 UK). Patients in Germany were older (79.8 years), often symptomatic (89.5%) and female (49.8%) and had a lower EF (53.8%) than patients in France and UK. Comorbidities were more common and they had a higher mean Euroscore II.Aortic valve replacement (AVR) was planned within 3 months in 70.2%. This was higher (p<0.001) in Germany than France/ UK. Of those with planned AVR, 82.3% received it within 3 months with a gradual decline (Germany>France> UK; p<0.001). In 253 patients, AVR was not performed, despite planned. Germany had a strong transcatheter aortic valve implantation (TAVI) preference (83.2%) versus France/ UK (p<0.001). Waiting time for TAVI was shorter in Germany (24.9 days) and France (19.5 days) than UK (40.3 days).Symptomatic patients were scheduled for an AVR in 79.4% (Germany> France> UK; p<0.001) and performed in 83.6% with a TAVI preference (73.1%). 20.4% of the asymptomatic patients were intervened.ConclusionPatients in Germany had more advanced disease. The rate of intervention within 3 months after diagnosis was startlingly low in the UK. Asymptomatic patients without a formal indication often underwent an intervention in Germany and France.
Multidisciplinary collaboration among young specialists: results of an international survey by the emerging EULAR network and other young organisations
Authors: Najm Aurélie , Kostine Marie , Pauling John D , Ferreira Ana Carina , Stevens Kate , Smith Evelyn , Eguiluz-Gracia Ibon , Studenic Paul , Rodríguez-Carrio Javier , Ramiro Sofia , Alunno Alessia , Richez Christophe , Nikiphorou Elena , Sepriano Alexandre 
Published: September 2020

BackgroundMultidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and research collaboration among young specialists and to identify unmet needs in this area.MethodsAn online survey was disseminated by email and social media to members of the EMerging EUlar NETwork, the Young Nephrologists’ Platform, the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers and the European Academy of Allergy and Clinical Immunology Junior Members.ResultsOf 303 respondents from 36 countries, 61% were female, 21% were aged below 30 years and 67% were aged 31–40 years. Young rheumatologists were the most represented (39%), followed by young nephrologists (24%), young paediatricians (20%), young allergologists (11%) then young internists (3%) and 3% other specialities. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1–2 days (85%) common courses including case discussion (81%) and training workshops (85%), as well as webinars recorded with several specialists on a specific disease (96%).ConclusionsThis collaborative initiative highlighted wishes from young specialists for developing (1) regular local multidisciplinary meetings to discuss complex patients, (2) clinical research collaboration with combined grants and (3) multidisciplinary online projects such as common courses, webinars and apps.
Changes in adults’ vaping and smoking behaviours associated with aerosol-free laws
Authors: Nguyen Hai V , Bornstein Stephen 
Published: September 2020

ObjectivesBanning e-cigarette use in public places has attracted considerable debate, with governments adopting different policies. However, little is known about the outcomes of such bans. We investigated the association of banning e-cigarette use in public places and workplaces in Canadian provinces with adults’ vaping and smoking behaviours.DesignDifference-in-differences.SettingNationally representative Canadian Tobacco Use Monitoring Survey (CTUMS) and Canadian Tobacco, Alcohol and Drugs Survey (CTADS).ParticipantsAdults aged 19 and older from CTADS 2013–2017 for e-cigarette outcomes (N=36 562) and from CTUMS/CTADS 2004–2017 for combustible cigarette outcomes (N=178 654).InterventionsBans on e-cigarette use in public places and workplaces in Canadian provinces.Main outcome measuresPast 30-day e-cigarette use, current combustible cigarette use, use of e-cigarettes when unable to smoke combustible cigarettes.ResultsAfter the bans, e-cigarette use in the past 30 days did not change significantly in provinces with a ban compared with provinces without a ban (0.004; 95% CI −0.025 to 0.032; p=0.783). The bans also had no impact on current combustible cigarette use (0.009; 95% CI −0.019 to 0.037; p=0.488). There is evidence of ban evasion among young people aged 19–24 who, after the bans, reported higher use of e-cigarettes when unable to smoke combustible cigarettes (0.114; 95% CI −0.023 to 0.250; p=0.092).ConclusionsTwo years after implementation, the aerosol-free laws in Canada had no impacton adults’ vaping and smoking behaviours. Policy efforts are urgently needed to improve the ban enforcement and to deal with discreet vaping among young adults.
Effect of bovine lactoferrin on prevention of late-onset sepsis in infants <1500 g: a pooled analysis of individual patient data from two randomized controlled trials
Authors: Ochoa Theresa , Loli Sebastian , Mendoza Karina , Carcamo Cesar , Bellomo Sicilia , Cam Luis , Castaneda Anne , Campos Miguel , Jacobs Jan , Cossey Veerle , Zegarra Jaime 
Published: September 2020

We previously conducted two randomized controlled trials with bovine lactoferrin (bLF) for the prevention of late-onset sepsis (LOS) in infants with a birth weight <2500 g (Study 1) and <2000 g (Study 2). The aim of this study was to determine the preventative effects of bLF on culture-proven or probable LOS in infants with a birth weight <1500 g from both studies, and to determine the effect of bLF in relation to intake of human milk. Both trial designs had similar inclusion and exclusion criteria, the same dose of bLF [200 mg·(kg body mass)–1·day–1], and used the same control (maltodextrin). We fitted multivariate Cox regression models to estimate the effect of bLF on the risk of development of the composite outcome, adjusting for covariates. We included 335 neonates with a mean birth weight of 1162 ± 244 g; 27.5% were <1000 g. There were 33 first episodes of LOS in the bLF treatment group and 48 in the control group (19.5% vs. 28.9%). bLF had a protective effect on the risk of development of LOS [hazard ratio (HR) = 0.64; %95 CI = 0.41–0.99; p = 0.048]; particularly among infants weighing <1000 g [HR = 0.46; %95 CI = 0.22–0.96; p = 0.039] and infants with a low intake of human milk [HR = 0.40; %95 CI = 0.19–0.84; p = 0.015]. Therefore, bLF supplementation protects infants <1500 g from LOS, particularly those infants not receiving human milk.
Iron-catalyzed cross-coupling of arylboronic acids with unactivated N-heterocycles and quinones under microwave heating
Authors: Start Keegan P. , Wheeler Mikhailey D. , Kozak Christopher M. 
Published: September 2020

The iron-catalyzed direct arylation of a variety of N-heteroarenes, quinones, and hydroquinones with arylboronic acids is investigated under microwave heating. The reaction proceeds at 70 °C under air using K2S2O8 as an oxidant and FeSO4 as a catalyst. Under microwave heating, reaction times decreased 14- to 115-fold. Reaction scope with N-heteroarenes and quinones is comparable with or slightly expanded when compared with previous reports, but the scope of arylboronic acid utility was slightly limited due to previously unobserved arylboronic acid hydroxydeboronation.
Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies
Authors: Park Derek S. , Luddy Kimberly A. , Robertson-Tessi Mark , O'Farrelly Cliona , Gatenby Robert A. , Anderson Alexander R.A. 
Published: September 2020

Abstract
Deaths from cancer are mostly due to metastatic disease that becomes resistant to therapy. A mainstay treatment for many cancers is chemotherapy, for which the dosing strategy is primarily limited by patient toxicity. While this MTD approach builds upon the intuitively appealing principle that maximum therapeutic benefit is achieved by killing the largest possible number of cancer cells, there is increasing evidence that moderation might allow host-specific features to contribute to success. We believe that a “Goldilocks Window” of submaximal chemotherapy will yield improved overall outcomes. This window combines the complex interplay of cancer cell death, immune activity, emergence of chemoresistance, and metastatic dissemination. These multiple activities driven by chemotherapy have tradeoffs that depend on the specific agents used as well as their dosing levels and schedule. Here we present evidence supporting the idea that MTD may not always be the best approach and offer suggestions toward a more personalized treatment regime that integrates insights into patient-specific eco-evolutionary dynamics.
Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers
Authors: Høgdall Dan , O'Rourke Colm J. , Dehlendorff Christian , Larsen Ole F. , Jensen Lars H. , Johansen Astrid Z. , Dang Hien , Factor Valentina M. , Grunnet Mie , Mau-Sørensen Morten , Oliveira Douglas V.N.P. , Linnemann Dorte , Boisen Mogens K. , Wang Xin W. , Johansen Julia S. , Andersen Jesper B. 
Published: September 2020

Abstract

Purpose:
Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity.

Experimental Design:
A total of 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017). Serum CA19-9, IL6, and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL6R and YKL-40 were assessed in vitro, and of IL6R inhibition in vivo.

Results:
High pretreatment levels of CA19-9, IL6, and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL6 provided independent prognostic information, independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL6 and YKL-40 were predictive of very short OS (OS &lt; 6 months), whereas CA19-9 was best to predict OS &gt; 1.5 years. Treatment with anti-IL6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an in vivo transplant model of BTC.

Conclusions:
Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.
Marine Annelida of India: taxonomy and status evaluation and an updated checklist
Authors: Sanitha K. Sivadas  , Russell Carvalho  
Published: September 2020

We present an updated checklist of marine annelids from the Indian subcontinent. Records of annelid species were obtained from published and grey literatures and online databases. Our review of annelid publications was restricted to the Indian continental shelf region. This paper also discusses the taxonomic status of marine annelid species recorded from this region and problems that impede its research. The updated list comprises of 727 species belonging to 334 genera and 72 families. A total of 152 species have their type locality in India including 88 species that are endemic to the region. The current checklist indicates that 25% (183 species) of the records are questionable and require further examination. Our results highlight that marine annelid richness of the Indian sub-continent is underestimated with many of the native undescribed species being most likely concealed under ‘erroneous’ or ‘cosmopolitan’ records. With a combination of factors that include a lack of experts, funding, and failure to update regional literature has resulted in an incomplete state of knowledge for the marine annelid biodiversity from this region. Therefore, there is an urgent need for extensive and intensive sampling to discover new species, conduct detailed re-examinations of doubtful records and, collaborate within the local and international institutes and organizations to improve the regional biodiversity studies.
Single-Cell RNA Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells
Authors: Paik David T. , Tian Lei , Williams Ian M. , Rhee Siyeon , Zhang Hao , Liu Chun , Mishra Ridhima , Wu Sean M. , Red-Horse Kristy , Wu Joseph C. 
Published: September 2020

Background:
Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably imprinted in the transcriptome, the pathways and networks that sustain EC heterogeneity have not been fully delineated.

Methods:
To investigate the transcriptomic basis of EC specificity, we analyzed single-cell RNA sequencing data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We used a number of bioinformatics tools to uncover markers and sources of EC heterogeneity from single-cell RNA sequencing data.

Results:

We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either single-cell RNA sequencing or bulk RNA sequencing, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (eg, liver, brain), whereas others (ie, adipose, heart) have considerable transcriptomic overlap with ECs from other tissues. We identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. Sex was a considerable source of heterogeneity in the endothelial transcriptome and we discovered
Lars2
to be a gene that is highly enriched in ECs from male mice. We found that markers of heart and lung ECs in mice were conserved in human fetal heart and lung ECs. We identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns.

Conclusions:

We used single-cell RNA sequencing data generated by the
Tabula Muris
consortium to uncover transcriptional networks that maintain tissue-specific EC identity and to identify novel angiocrine and functional relationships between tissue-specific ECs.