bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of remote monitoring on patient-reported outcomes in European heart failure patients with an implantable cardioverter-defibrillator: primary results of the REMOTE-CIED randomized trial
Authors: Versteeg Henneke , Timmermans Ivy , Widdershoven Jos , Kimman Geert-Jan , Prevot Sébastien , Rauwolf Thomas , Scholten Marcoen F , Zitron Edgar , Mabo Philippe , Denollet Johan , Pedersen Susanne S , Meine Mathias 
Published: April 2019

AbstractAimsThe European REMOTE-CIED study is the first randomized trial primarily designed to evaluate the effect of remote patient monitoring (RPM) on patient-reported outcomes in the first 2 years after implantation of an implantable cardioverter-defibrillator (ICD).Methods and resultsThe sample consisted of 595 European heart failure patients implanted with an ICD compatible with the Boston Scientific LATITUDE® RPM system. Patients were randomized to RPM plus a yearly in-clinic ICD check-up vs. 3–6-month in-clinic check-ups alone. At five points during the 2-year follow-up, patients completed questionnaires including the Kansas City Cardiomyopathy Questionnaire and Florida Patient Acceptance Survey (FPAS) to assess their heart failure-specific health status and ICD acceptance, respectively. Information on clinical status was obtained from patients’ medical records. Linear regression models were used to compare scores between groups over time. Intention-to-treat and per-protocol analyses showed no significant group differences in patients’ health status and ICD acceptance (subscale) scores (all Ps > 0.05). Exploratory subgroup analyses indicated a temporary improvement in device acceptance (FPAS total score) at 6-month follow-up for secondary prophylactic in-clinic patients only (P < 0.001). No other significant subgroup differences were observed.ConclusionLarge clinical trials have indicated that RPM can safely and effectively replace most in-clinic check-ups of ICD patients. The REMOTE-CIED trial results show that patient-reported health status and ICD acceptance do not differ between patients on RPM and patients receiving in-clinic check-ups alone in the first 2 years after ICD implantation.ClinicalTrials.gov Identifier: NCT01691586.
Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project
Authors: Di Carlo Antonio , Bellino Leonardo , Consoli Domenico , Mori Fabio , Zaninelli Augusto , Baldereschi Marzia , Cattarinussi Alessandro , D’Alfonso Maria Grazia , Gradia Chiara , Sgherzi Bruno , Pracucci Giovanni , Piccardi Benedetta , Polizzi Biancamaria , Inzitari Domenico ,   National Research Program: Progetto FAI. La Fibrillazione Atriale in Italia, Aliprandi M L , Bonsangue E , Locatelli P , Saurgnani P , Senziani L G , Tarantini D , Rota Rita Paola , Boninsegni R , Feltrin T , Lancia E , Latella F , Monici G , Portera F , Ceccherini S , Borello G , Contartese A , D’Amico A , D’Urzo G , Grillo G C , Mellea F , Ramondino C 
Published: April 2019

Abstract

Aims
To estimate prevalence of atrial fibrillation (AF) in a representative sample of the Italian elderly population, projecting figures for Italy and the European Union.

Methods and results
A cross-sectional examination of all subjects aged 65+ years from three general practices in Northern, Central, and Southern Italy started in 2016. Participants were administered a systematic and an opportunistic screening, followed by clinical and electrocardiogram confirmation. The study sample included 6016 subjects. Excluding 235 non-eligible, among the remaining 5781 participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Prevalence of AF was 7.3% [95% confidence intervals (CI) 6.6–8.1], higher in men and with advancing age (6.6% from systematic plus 0.7% from opportunistic screening). Using prevalence figures, Italian elderly having AF in 2016 were estimated at ∼1 081 000 (95% CI 786 000–1 482 000). Considering stable prevalence, this number will increase by 75% to ∼1 892 000 in 2060 (95% CI 1 378 000–2 579 000). European Union elderly having AF in 2016 were estimated at ∼7 617 000 (95% CI 5 530 000–10 460 000), increasing by 89% to ∼14 401 000 in 2060 (95% CI 10 489 000–19 647 000). In 2016, subjects aged 80+ years represented 53.5% of cases in Italy and 51.2% in the European Union; in 2060, 69.6% and 65.2%, respectively.

Conclusions
Our findings indicate a high burden of AF in coming decades, especially among the oldest-old, who carry the higher AF-related risk of stroke and medical complications.
Modulation of Adaptive Cognitive Control by Prefrontal High-Definition Transcranial Direct Current Stimulation in Older Adults
Authors: Gbadeyan Oyetunde , Steinhauser Marco , Hunold Alexander , Martin Andrew K , Haueisen Jens , Meinzer Marcus 
Published: April 2019

Abstract

Objective
Adaptive cognitive control frequently declines in advanced age. Because high-definition transcranial direct current stimulation (HD-tDCS) of the right dorsolateral prefrontal cortex (DLPFC) improved cognitive control in young adults, we investigated if this montage can also improve cognitive control in older individuals.

Method
In a double-blind, sham HD-tDCS controlled, cross-over design, 36 older participants received right DLPFC HD-tDCS during a visual flanker task. Conflict adaptation (CA) effects on response time (RT) and error rates (ER) assessed adaptive cognitive control. Biophysical modeling assessed the magnitude and distribution of induced current in older adults.

Results
Active HD-tDCS enhanced CA in older adults. However, this positive behavioral effect was limited to CA in ER. Similar to results obtained in healthy young adults, current modeling analysis demonstrated focal current delivery to the DLPFC with sufficient magnitude of the induced current to modulate neural function in older adults.

Discussion
This study confirms the effectiveness of HD-tDCS to modulate adaptive cognitive control in advanced age.
Duphold: scalable, depth-based annotation and curation of high-confidence structural variant calls
Authors: Pedersen Brent S , Quinlan Aaron R 
Published: April 2019

Abstract
Most structural variant (SV) detection methods use clusters of discordant read-pair and split-read alignments to identify variants yet do not integrate depth of sequence coverage as an additional means to support or refute putative events. Here, we present "duphold," a new method to efficiently annotate SV calls with sequence depth information that can add (or remove) confidence to SVs that are predicted to affect copy number. Duphold indicates not only the change in depth across the event but also the presence of a rapid change in depth relative to the regions surrounding the break-points. It uses a unique algorithm that allows the run time to be nearly independent of the number of variants. This performance is important for large, jointly called projects with many samples, each of which must be evaluated at thousands of sites. We show that filtering on duphold annotations can greatly improve the specificity of SV calls. Duphold can annotate SV predictions made from both short-read and long-read sequencing datasets. It is available under the MIT license at https://github.com/brentp/duphold.
Recent advances in understanding the effects of climate change on the world’s oceans
Authors: Hollowed Anne B , Barange Manuel , Garçon Véronique , Ito Shin-ichi , Link Jason S , Aricò Salvatore , Batchelder Harold , Brown Robin , Griffis Roger , Wawrzynski Wojciech 
Published: April 2019

Abstract
In June 2018, >600 scientists from over 50 countries attended the Fourth International Symposium on the Effects of Climate Change on the World’s Oceans (ECCWO-4). ECCWO-4 provided a forum for scientists to share information, build understanding, and advance responses to climate impacts on oceans and the many people, businesses and communities that depend on them. Seven Key Messages emerging from the symposium and relevant information from recently published literature are summarized. Recent scientific advances are improving our ability to understand, project, and assess the consequences of different levels of 21st century climate change for ocean ecosystems and ocean dependent communities. Outcomes of the symposium highlighted the need for on-going engagement with stakeholders, communities, and managers when considering the trade-offs associated with tactical and strategic opportunities for adaptation to climate change. Science informed adaptation frameworks that engage the public in their development are needed for effective management of marine resources in a changing climate. The summary provides a brief overview of the advances in climate-ocean science emerging from the symposium and provides context for the contributed papers within the broader socio-ecological advances of the discipline.
Pharmacokinetics of adjusted-dose 8-hourly lopinavir/ritonavir in HIV-infected children co-treated with rifampicin
Authors: Rabie Helena , Rawizza Holly , Zuidewind Peter , Winckler Jana , Zar Heather , Van Rie Annelies , Wiesner Lubbe , McIlleron Helen 
Published: April 2019

AbstractObjectivesTo evaluate the proportion of children with lopinavir Cmin ≥1 mg/L when receiving a novel 8-hourly lopinavir/ritonavir dosing strategy during rifampicin co-treatment.MethodsHIV-infected children on lopinavir/ritonavir and rifampicin were enrolled in a prospective pharmacokinetic study. Children were switched from standard-of-care lopinavir/ritonavir-4:1 with additional ritonavir (1:1 ratio) twice daily to 8-hourly lopinavir/ritonavir-4:1 using weight-banded dosing. Rifampicin was dosed at 10–20 mg/kg/day. After 2 weeks, plasma samples were collected ∼2, 4, 6, 8 and 10 h after the morning lopinavir/ritonavir-4:1 dose, ALT was obtained to assess safety and treatment was switched back to standard of care. ClinicalTrials.gov registration number: NCT01637558.ResultsWe recruited 11 children in two weight bands: 5 (45%) were 10–13.9 kg and received 20–24 mg/kg/dose of lopinavir and 6 (55%) children weighed 6–9.9 kg and received 20–23 mg/kg/dose of lopinavir. The median age was 15 months (IQR = 12.6–28.8 months). The median (IQR) lopinavir Cmin was 3.0 (0.1–5.5) mg/L. Seven (63.6%) of the 11 children had Cmin values ≥1 mg/L. Children with a lopinavir mg/kg dose below the median 21.5 were more likely to have Cmin <1 mg/L (P = 0.02). There was a strong positive correlation between lopinavir and ritonavir concentrations. No associations were found between lopinavir AUC2–10 and age, sex, weight, nutritional status or mg/kg/dose of lopinavir.ConclusionsThese data do not support the use of 8-hourly lopinavir/ritonavir at studied doses. Evaluation of higher doses is needed to optimize treatment outcomes of TB and HIV in young children.
Unravelling ceftazidime/avibactam resistance of KPC-28, a KPC-2 variant lacking carbapenemase activity
Authors: Oueslati Saoussen , Iorga Bogdan I , Tlili Linda , Exilie Cynthia , Zavala Agustin , Dortet Laurent , Jousset Agnès B , Bernabeu Sandrine , Bonnin Rémy A , Naas Thierry 
Published: April 2019

AbstractBackgroundKPC-like carbapenemases have spread worldwide with more than 30 variants identified that differ by single or double amino-acid substitutions.ObjectivesTo describe the steady-state kinetic parameters of KPC-28, which differs from KPC-2 by a H274Y substitution and the deletion of two amino acids (Δ242-GT-243).MethodsThe blaKPC-2, blaKPC-3, blaKPC-14 and blaKPC-28 genes were cloned into a pTOPO vector for susceptibility testing or into pET41b for overexpression, purification and subsequent kinetic parameter (Km, kcat) determination. Molecular docking experiments were performed to explore the role of the amino-acid changes in the carbapenemase activity.ResultsSusceptibility testing revealed that Escherichia coli producing KPC-28 displayed MICs that were lower for carbapenems and higher for ceftazidime and ceftazidime/avibactam as compared with KPC-2. The catalytic efficiencies of KPC-28 and KPC-14 for imipenem were 700-fold and 200-fold lower, respectively, than those of KPC-2, suggesting that Δ242-GT-243 in KPC-28 and KPC-14 is responsible for reduced carbapenem hydrolysis. Similarly, the H274Y substitution resulted in KPC-28 in a 50-fold increase in ceftazidime hydrolysis that was strongly reversed by clavulanate.ConclusionsWe have shown that KPC-28 lacks carbapenemase activity, has increased ceftazidime hydrolytic activity and is strongly inhibited by clavulanate. KPC-28-producing E. coli isolates display an avibactam-resistant ESBL profile, which may be wrongly identified by molecular and immunochromatographic assays as the presence of a carbapenemase. Accordingly, confirmation of carbapenem hydrolysis will be mandatory with assays based solely on blaKPC gene or gene product detection.
Not just a cargo receptor for large cargoes; an emerging role of TANGO1 as an organizer of ER exit sites
Authors: Saito Kota , Maeda Miharu 
Published: April 2019

Abstract
Proteins synthesized within the endoplasmic reticulum (ER) are exported from ER exit sites via coat protein complex II (COPII)-coated vesicles. Although the mechanisms of COPII-vesicle formation at the ER exit sites are highly conserved among species, vertebrate cells secrete a wide range of materials, including collagens and chylomicrons, which form bulky structures within the ER that are too large to fit into conventional carriers. Transport ANd Golgi Organization 1 (TANGO1) was initially identified as a cargo receptor for collagens but has been recently rediscovered as an organizer of ER exit sites. We would like to review recent advances in the mechanism of large cargo secretion and organization of ER exit sites through the function of TANGO1.
Survival Differences Between Males and Females Diagnosed With Childhood Cancer
Authors: Williams Lindsay A , Spector Logan G 
Published: April 2019

Abstract

Background
Males have worse survival for childhood cancer, but whether this disparity exists among all childhood cancer types is undescribed.

Methods
We estimated sex differences in survival for 18 cancers among children (0–19 years) in Surveillance, Epidemiology, and End Results 18 (2000–2014). We used Kaplan-Meier survival curves (log-rank P values) to characterize sex differences in survival and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between sex and death for each cancer type. We used an inverse odds weighting method to determine whether the association between sex and death was mediated by stage of disease for solid tumors.

Results
Males had worse overall survival and a higher risk of death for acute lymphoblastic leukemia (HR = 1.24, 95% CI = 1.12 to 1.37), ependymoma (HR = 1.36, 95% CI = 1.05 to 1.77), neuroblastoma (HR = 1.28, 95% CI = 1.09 to 1.51), osteosarcoma (HR = 1.29, 95% CI = 1.08 to 1.53), thyroid carcinoma (HR = 3.25, 95% CI = 1.45 to 7.33), and malignant melanoma (HR = 1.97, 95% CI = 1.33 to 2.92) (all log-rank P values < .02). The association between sex and death was mediated by stage of disease for neuroblastoma (indirect HR = 1.12, 95% CI = 1.05 to 1.19), thyroid carcinoma (indirect HR = 1.24, 95% CI = 1.03 to 1.48), and malignant melanoma (indirect HR = 1.28, 95% CI = 1.10 to 1.49). For these six tumors, if male survival had been as good as female survival, 21% of male deaths and 13% of total deaths after these cancer diagnoses could have been avoided.

Conclusions
Consideration of molecular tumor and clinical data may help identify mechanisms underlying the male excess in death after childhood cancer for the aforementioned cancers.
The fate of planetesimal discs in young open clusters: implications for 1I/’Oumuamua, the Kuiper belt, the Oort cloud, and more
Authors: Hands T O , Dehnen W , Gration A , Stadel J , Moore B 
Published: April 2019

ABSTRACT
We perform N-body simulations of the early phases of open cluster evolution including a large population of planetesimals, initially arranged in Kuiper-belt like discs around each star. Using a new, fourth-order, and time-reversible N-body code on Graphics Processing Units (GPUs), we evolve the whole system under the stellar gravity, i.e. treating planetesimals as test particles, and consider two types of initial cluster models, similar to IC348 and the Hyades, respectively. In both cases, planetesimals can be dynamically excited, transferred between stars, or liberated to become free-floating (such as A/2017 U1 or ’Oumuamua) during the early cluster evolution. We find that planetesimals captured from another star are not necessarily dynamically distinct from those native to a star. After an encounter, both native and captured planetesimals can exhibit aligned periastrons, qualitatively similar to that seen in the Solar system and commonly thought to be the signature of Planet 9. We discuss the implications of our results for both our Solar system and exoplanetary systems.
CmTCP20 Plays a Key Role in Nitrate and Auxin Signaling-Regulated Lateral Root Development in Chrysanthemum
Authors: Fan Hong-Mei , Sun Cui-Hui , Wen Li-Zhu , Liu Bo-Wen , Ren Hong , Sun Xia , Ma Fang-Fang , Zheng Cheng-Shu 
Published: April 2019

Abstract
Lateral root (LR) formation and development play a vital role in plant development by permitting the establishment of branched root systems. It is well known that nutrient availability controls LR development. Moreover, LR development is fine-tuned by a myriad of hormonal signals. Many transcription factors (TFs) participate in LR development. Here, we discuss the TFs involved in the nitrate and auxin signaling pathways and how these function in the regulation of LR formation and development in chrysanthemum. AtTCP20 is a plant-specific TF, which can modulate LR development in response to nitrate. The roles of CmTCP20 in LR development were identified by overexpression in chrysanthemum and heterologous expression in Arabidopsis. Overexpression of CmTCP20 significantly increased the number and average length of LRs compared with the wild type in chrysanthemum and Arabidopsis. We also found that CmTCP20 positively influenced auxin accumulation in the LRs at least partly by improving auxin biosynthesis, transport and response, thereby promoting LR development. Moreover, we found that CmTCP20 interacts with an auxin response factor, CmARF8, which also can be induced by nitrate and combined to proximal sites in the upstream promoter region of CmCYCB1;1 to positively regulate the cell cycle. The CmTCP20-CmARF8 heterodimer links nitrate and auxin signaling and converts cell-cycle signals to regulate LR initiation and growth.
Gibberellins Play a Role in Regulating Tomato Fruit Ripening
Authors: Li Hu , Wu Han , Qi Qi , Li Huihui , Li Zhifei , Chen Shen , Ding Qiangqiang , Wang Quanzhi , Yan Zhiming , Gai Ying , Jiang Xiangning , Ding Jing , Gu Tingting , Hou Xilin , Richard McAvoy , Zhao Yunde , Li Yi 
Published: April 2019

AbstractAlthough exogenous applications of gibberellins (GAs) delay tomato ripening, the regulatory mechanisms of GAs in the process have never been well recognized. Here, we report that the concentration of endogenous GAs is declined before the increase of ethylene production in mature-green to breaker stage fruits. We further demonstrate that reductions in GA levels via overexpression of a GA catabolism gene SlGA2ox1 specifically in fruit tissues lead to early ripening. Consistently, we have also observed that application of a GA biosynthetic inhibitor, prohexadione-calcium, at the mature-green stage accelerates fruit ripening, while exogenous GA3 application delays the process. Furthermore, we demonstrate that ethylene biosynthetic gene expressions and ethylene production are activated prematurely in GA-deficient fruits but delayed/reduced in exogenous GA3-treated WT fruits. We also show that the GA deficiency-mediated activation of ethylene biosynthesis is due to the activation of the ripening regulator genes RIN, NOR and CNR. In conclusion, our results demonstrate that GAs play a negative role in tomato fruit ripening.
Genome-Wide Analysis of Phospholipase D Gene Family and Profiling of Phospholipids under Abiotic Stresses in Brassica napus
Authors: Lu Shaoping , Fadlalla Tarig , Tang Shan , Li Long , Ali Usman , Li Qing , Guo Liang 
Published: April 2019

Abstract
Oil crop Brassica napus is subjected to environmental stresses such as drought, cold and salt. Phospholipase Ds (PLDs) have vital roles in regulation of plant growth, development and stress tolerance. In this study, 32 BnaPLD genes were identified and classified into six subgroups depending on the conserved protein structures. High similarity in gene and protein structures exists between BnaPLDs and AtPLDs. Gene expression analysis showed that BnaPLDα1s and BnaPLDδs had higher expression than other PLDs. BnaPLDα1 and BnaPLDδ were significantly induced by abiotic stresses including dehydration, NaCl, abscisic acid (ABA) and 4ï¿½C. Lipidomic analysis showed that the content of main membrane phospholipids decreased gradually under stresses, except phosphatidylglycerol increased under the treatment of ABA and phosphatidylethanolamine increased under 4ï¿½C. Correspondingly, their product of phosphatidic acid increased often with a transient peak at 8 h. The plant height of mutants of PLDα1 was significantly reduced. Agronomic traits such as yield, seed number, silique number and branches were significantly impaired in PLDα1 mutants. These results indicate that there is a large family of PLD genes in B. napus, especially BnaPLDα1s and BnaPLDδs may play important roles in membrane lipids remodeling and maintaining of the growth and stress tolerance of B. napus.
Sperm Entry into the Egg Cell Induces the Progression of Karyogamy in Rice Zygotes
Authors: Ohnishi Yukinosuke , Kokubu Iwao , Kinoshita Tetsu , Okamoto Takashi 
Published: April 2019

Abstract
Karyogamy is a prerequisite event for plant embryogenesis, in which dynamic changes in nuclear architecture and the establishment of appropriate gene expression patterns must occur. However, the precise role of the male and female gametes in the progression of karyogamy still remains elusive. Here, we show that the sperm cell possesses the unique property to drive steady and swift nuclear fusion. When we fertilized egg cells with sperm cells in vitro, the immediate fusion of the male and female nuclei in the zygote progressed. This rapid nuclear fusion did not occur when two egg cells were artificially fused. However, the nuclear fusion of two egg nuclei could be accelerated by additional sperm entry or the exogenous application of calcium, suggesting that possible increase of cytosolic Ca2+ level via sperm entry into the egg cell efficiently can facilitate karyogamy. In contrast to zygotes, the egg–egg fusion cells failed to proliferate beyond an early developmental stage. Our transcriptional analyses also revealed the rapid activation of zygotic genes in zygotes, whereas there was no expression in fused cells without the male contribution. Thus, the male sperm cell has the ability to cause immediate karyogamy and to establish appropriate gene expression patterns in the zygote.
Fillings and fittings of unit cotangent bundles of odd-dimensional spheres
Authors: Kwon Myeonggi , Zehmisch Kai 
Published: April 2019

AbstractWe introduce the concept of fittings to symplectic fillings of the unit cotangent bundle of odd-dimensional spheres. Assuming symplectic asphericity we show that all fittings are diffeomorphic to the respective unit co-disc bundle.