bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Trends in the Incidence and Outcomes of Pacemaker Implantation After Transcatheter Aortic Valve Replacement in the United States (2012–2017)
Authors: Kawsara Akram , Sulaiman Samian , Alqahtani Fahad , Eleid Mackram F. , Deshmukh Abhishek J. , Cha Yong‐Mei , Rihal Charanjit S. , Alkhouli Mohamad 
Published: August 2020

Background
Nationwide studies documenting temporal trends in permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR) are limited.

Methods and Results

We selected patients who underwent TAVR between 2012 and 2017 in the National Readmission Database. The primary end point was the 6‐year trend in post‐TAVR PPMI at index hospitalization and at 30, 90, and 180 days after discharge. The secondary end point was the association between PPMI and in‐hospital mortality, stroke, cost, length of stay, and disposition. Among the 89 202 patients who underwent TAVR, 77 405 (86.8%) with no prior pacemaker or defibrillator were included. Patients who required PPMI had a higher prevalence of atrial fibrillation (43.6% versus 38.7%,
P
<0.001) and conduction abnormalities (28.4% versus 15.3%,
P
<0.001). The incidence of PPMI during index admission increased from 8.7% in 2012 to 13.2% in 2015, and then decreased to 9.6% in 2017. The incidence of inpatient PPMI within 30 days after discharge increased from 0.5% in 2012 to 1.25% in 2017 (
P
trend
<0.001). Inpatient PPMI beyond 30 days remained rare (<0.5%) during the study period. After risk adjustment, PPMI was not associated with in‐hospital mortality or stroke but was associated with increased nonhome discharge, longer hospitalization, and higher cost. The incremental expenditure associated with post‐TAVR PPMI during index admission increased from $9.6 million to $72.2 million between 2012 and 2017.

Conclusions
After an upward trend, rates of PPMI after TAVR in the United States stabilized at ~10% in 2016 to 2017, but there was a notable increase in PPMI within 30 days after the index admission. PPMI was not associated with increased in‐hospital morbidity or mortality but led to longer hospitalization, higher cost, and more nonhome discharges.
MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin‐Producing Reparative Macrophages After Myocardial Infarction
Authors: Shirakawa Kohsuke , Endo Jin , Kataoka Masaharu , Katsumata Yoshinori , Anzai Atsushi , Moriyama Hidenori , Kitakata Hiroki , Hiraide Takahiro , Ko Seien , Goto Shinichi , Ichihara Genki , Fukuda Keiichi , Minamino Tohru , Sano Motoaki 
Published: August 2020

Background

We previously reported that osteopontin plays an essential role in accelerating both reparative fibrosis and clearance of dead cells (efferocytosis) during tissue repair after myocardial infarction (MI) and galectin‐3
hi
CD206
+
macrophages is the main source of osteopontin in post‐MI heart. Interleukin‐10– STAT3 (signal transducer and activator of transcription 3)–galectin‐3 axis is essential for
Spp1
(encoding osteopontin) transcriptional activation in cardiac macrophages after MI. Here, we investigated the more detailed mechanism responsible for functional maturation of osteopontin‐producing macrophages.

Methods and Results

In post‐MI hearts,
Spp1
transcriptional activation occurred almost exclusively in MerTK (Mer tyrosine kinase)
+
galectin‐3
hi
macrophages. The induction of MerTK on galectin‐3
hi
macrophages is essential for their functional maturation including efferocytosis and
Spp1
transcriptional activity. MerTK
+
galectin‐3
hi
macrophages showed a strong activation of both STAT3 and ERK (extracellular signal‐regulated kinase). STAT3 inhibition suppressed the differentiation of osteopontin‐producing MerTK
+
galectin‐3
hi
macrophages, however, STAT3 activation was insufficient at inducing
Spp1
transcriptional activity. ERK inhibition suppressed
Spp1
transcriptional activation without affecting MerTK or galectin‐3 expression. Concomitant activation of ERK is required for transcriptional activation of
Spp1
. In
Il‐10
knockout enhanced green fluorescent protein–
Spp1
knock‐in mice subjected to MI, osteopontin‐producing macrophages decreased but did not disappear entirely. Interleukin‐10 and macrophage colony‐stimulating factor synergistically activated STAT3 and ERK and promoted the differentiation of osteopontin‐producing MerTK
+
galectin‐3
hi
macrophages in bone marrow–derived macrophages. Coadministration of anti‐interleukin‐10 plus anti–macrophage colony‐stimulating factor antibodies substantially reduced the number of osteopontin‐producing macrophages by more than anti–interleukin‐10 antibody alone in post‐MI hearts.

Conclusions
Interleukin‐10 and macrophage colony‐stimulating factor act synergistically to activate STAT3 and ERK in cardiac macrophages, which in turn upregulate the expression of galectin‐3 and MerTK, leading to the functional maturation of osteopontin‐producing macrophages.
Following the Leaders? How to Restore Progress in Global Climate Governance
Authors: Busby Joshua W. , Urpelainen Johannes 
Published: August 2020

AbstractThe Paris Agreement is in trouble. Here we assess the potential for climate leaders to bring the global climate regime back on track by developing a strategic understanding of followership. In other words, leaders need to know how to encourage other actors to follow them. We develop a typology of follower types—Enthusiasts, Pliables, Reluctants, and Hard Nuts—distinguished based on motivation and capacity. We identify the scope for a participation cascade based on the distribution of follower types. We argue that achieving a participation cascade may be more likely if leaders appreciate three insights from theories of collective action. First, break down the climate mitigation problem into smaller, more manageable challenges, such as sectoral approaches. Second, prioritize major emitters and areas with high mitigation potential and politically feasible action. Finally, emphasize benefits to potential followers. Together, the strategies can help reduce the number of Hard Nut cases by making the cost/benefit calculus more attractive to prospective followers.
Estimating the Maximum Vertical Velocity at the Leading Edge of a Density Current
Authors: Reif Dylan W. , Bluestein Howard B. , Weckwerth Tammy M. , Wienhoff Zachary B. , Chasteen Manda B. 
Published: August 2020

AbstractThe maximum upward vertical velocity at the leading edge of a density current is commonly <10 m s−1. Studies of the vertical velocity, however, are relatively few, in part owing to the dearth of high-spatiotemporal-resolution observations. During the Plains Elevated Convection At Night (PECAN) field project, a mobile Doppler lidar measured a maximum vertical velocity of 13 m s−1 at the leading edge of a density current created by a mesoscale convective system during the night of 15 July 2015. Two other vertically pointing instruments recorded 8 m s−1 vertical velocities at the leading edge of the density current on the same night. This study describes the structure of the density current and attempts to estimate the maximum vertical velocity at their leading edges using the following properties: the density current depth, the slope of its head, and its perturbation potential temperature. The method is then be applied to estimate the maximum vertical velocity at the leading edge of density currents using idealized numerical simulations conducted in neutral and stable atmospheres with resting base states and in neutral and stable atmospheres with vertical wind shear. After testing this method on idealized simulations, this method is then used to estimate the vertical velocity at the leading edge of density currents documented in several previous studies. It was found that the maximum vertical velocity can be estimated to within 10%–15% of the observed or simulated maximum vertical velocity and indirectly accounts for parameters including environmental wind shear and static stability.
Likelihood of Aortic Valve Preservation During Repair of Acute Type A Aortic Dissection
Authors: Thornhill Rosanne , Shih Wendy , Amen Marvin I. , John Mohan M. , Floridia Rosario , Razzouk Anees J. , Rabkin David G. 
Published: August 2020

Background We sought risk factors for replacement of the aortic valve with or without the root (AVR/root) in the setting of acute type A aortic dissection (ATAD) repair. Methods All ATAD repairs at our institution from January 2005 to June 2018 were reviewed. Baseline characteristics were recorded. For patients with aortic valve preservation, we documented the degree of aortic insufficiency (AI) postoperatively and on subsequent echocardiograms when available. Logistic regression was used to determine the association between preoperative characteristics and the odds ratio of AVR/root. Results 206 patients underwent repair of ATAD. Thirty-four were excluded for no documented AI grading. Forty-six underwent AVR/root during repair of the ATAD (including 40 root replacements). Of 126 that did not undergo AVR/root, 42 (33.33%) had follow-up echocardiograms at a median of 68 months postoperatively, 2 required reintervention for valve insufficiency. An increase in the degree of AI, bicuspid valve morphology, size of the aortic root, and connective tissue disorder was significantly associated with increased risk of AVR/root. Of 130 patients without connective tissue disorder, bicuspid aortic valve, aortic root aneurysm or intimal root tear, the rate of valve preservation was 65/65 (100%), 25/29 (86.2%), and 22/40 (55%) for those presenting with mild, moderate, and severe AI, respectively. Conclusion The degree of preoperative AI, bicuspid valve morphology, size of the aortic root, and connective tissue disorder significantly correlate with the failure of aortic valve preservation in patients with ATAD. The vast majority of tricuspid valves in patients without connective tissue disorder or aortic root pathology can be salvaged.
Laryngeal Langerhans Cell Histiocytosis: A Case Report and Literature Review
Authors: Zhou Allen S. , Li Lei , Carroll Thomas L. 
Published: August 2020

Objective: To describe a case of laryngeal Langerhans cell histiocytosis, discuss its characteristic features and management, and provide a review of the available literature. Methods: A patient presenting to a tertiary care medical center with dyspnea and hoarseness is described. A literature review of laryngeal Langerhans cell histiocytosis cases was performed through a search of articles indexed in the National Institutes of Health PubMed system. Results: We report a case of a 69-year old male, who presented with a laryngeal mass highly suspicious for laryngeal squamous cell carcinoma, was treated with laser excision, and was subsequently found to have laryngeal Langerhans cell histiocytosis upon histological analysis. Including our current case, we found six prior reported cases of laryngeal Langerhans cell histiocytosis in the literature. Of the six cases, four were in adults, while two were in children. Dyspnea is a common presenting complaint present in all cases. Smoking may be a potential risk factor. Conclusions: Laryngeal Langerhans cell histiocytosis is a rare condition and an important consideration in the differential diagnosis of patients presenting with a laryngeal mass and symptoms of dyspnea or hoarseness. Biopsy and histopathological analysis are key to the diagnosis. Surgical excision and radiotherapy are successful treatments used in clinical practice.
Off-Label Drug Use in Pediatric Out-Patient Care: A Multi-Center Observational Study
Authors: AlAzmi Aeshah , Alasmari Zahra , Yousef Consuela , Alenazi Ahmed , AlOtaibi Mohammed , AlSaedi Hani , AlShaikh Adnan , AlObathani Amani , Ahmed Omaima , Goronfolah Loie , Alahmari Mousa 
Published: August 2020

Objective: Prescribing a drug for a child is not an easy task and requires using the best available evidence as a guide, especially when a drug is used off-label. The practice of prescribing a drug for off-label use is fairly widespread worldwide. The FDA does not regulate prescribing patterns or practices of individual practitioners and, therefore, allows off-label use. The main objective of this study is to evaluate off-label prescribing among the pediatric population in the Kingdom of Saudi Arabia (KSA). Method: This is a retrospective, simple random selection observational study of children (≤15 years) who visited pediatric clinics and had at least 1 drug prescribed over a 12-month period (January to December 2018). Results: A total of 865 drugs (mean 1 and SD 0.24) were prescribed to 326 children. Off-label was identified in 39.4% of the drugs with a frequency of 512 (as 1 drug may belong to more than 1 off-label category). The most common reason for off-label prescribing was related to doses that were “higher or lower than the recommended use” (48.6%), and the most frequently identified drug class prescribed for off-label use was anti-infective drugs for systemic use (39.9%). The percentage of off-label drug use was found to be higher in girls and in the age group of 1 month to 2 years ( P = .001) for both variables. In addition, a significant association was found between off label drug use and the total number of drugs prescribed, P < .001. Conclusion: The findings of this study showed a high incidence of off-label prescribing mainly related to dosing and indication. The results of this observational study support the need to establish a unified national pediatric dosing formulary guide to ensure safe drug use in pediatrics.
Low pelvic incidence is a risk factor for intraoperative complications in minimally invasive anterolateral approach for total hip arthroplasty
Authors: Kim Youngwoo , Pour Aidin Eslam , Lazennec Jean Yves 
Published: August 2020

Background: Minimally invasive anterolateral approach (ALA) has gained popularity in recent years as better postoperative functional recovery and lower risk of postoperative dislocation are claimed. However, difficulties for femur exposure and intraoperative complications during femoral canal preparation and component placement have been reported. This study analyses the effect of anatomical factors on difficulties for femoral access and intraoperative complications with a modified minimally invasive ALA. Material and methods: 310 consecutive patients who had primary unilateral total hip arthroplasty (THA) by single surgeon using same approach and technique, and being suitable for EOS were included. All patients underwent pre- and postoperative standing and sitting full-body EOS acquisitions and pelvic and femoral parameters were measured. All intra- and postoperative complications for femoral preparation and implantation were assessed. Intraoperative complications included femoral fractures and difficulties for femoral exposure. Results: 10 patients (3.2%) had intraoperative femoral fractures (2 greater trochanter, 8 calcar). Difficult access to the proximal femur was reported for 10 other patients (3.2%). Patients with intraoperative complications presented a significantly lower pelvic incidence (PI) than patients without intraoperative complications (mean PI: 39.4° vs. 56.9°, p < 0.001). Conclusions: The pelvic incidence can be useful to detect anatomically less favourable patients for THA implantation using ALA.
Health-Related Quality of Life after Hip and Knee Arthroplasty Operations
Authors: Miettinen Hannu J. A. , Mäkirinne-Kallio Ninna , Kröger Heikki , Miettinen Simo S. A. 
Published: August 2020

Background and objective: The aim of this study was to investigate the health-related quality of life before and after a hip and a knee arthroplasty operation using a 15D instrument and to compare these scores to the Finnish control population 15D scores. Methods: The pre- and post-operative data of 15D were prospective collected from the patients undergoing total hip arthroplasty or total knee arthroplasty at the Kuopio University Hospital. Post-operative data were collected at 6 and 12 months after the operation. Results: The mean change of the 15D score after hip arthroplasty was +0.062 and after knee arthroplasty, it was +0.033 at the 12-month follow-up ( p < 0.001). Total hip arthroplasty patients of all ages reached the control population 15D scores at the 12-month follow-up. Of the total knee arthroplasty patients, only patients aged >75 years and males aged 55–64 years did reach control population 15D scores at the 12-month follow-up. Patients experienced a statistically significant improvement in mobility, vision, sleeping, usual activities, discomfort and symptoms, distress, and vitality ( p < 0.05). Conclusions: Successful hip and knee arthroplasty operations improve patients’ health-related quality of life. According to this study, hip arthroplasty improves the health-related quality of life more than knee arthroplasty.
Young adolescents’ interest in a mental health casual video game
Authors: Pine Russell , Sutcliffe Kylie , McCallum Simon , Fleming Theresa 
Published: August 2020

Background Mental distress and disorders among adolescents are well documented. Despite the array of treatments available, many mental health issues remain untreated and often undiagnosed. In an attempt to narrow the treatment gap, researchers have adapted existing mental health interventions into digital formats. Despite their efficacy in trial settings, however, real-world uptake of digital mental health interventions is typically low. Casual video games (CVGs) are popular among adolescents and may be a promising tool to reduce stress, anxiety and depression. Aim We set out to explore young adolescents’ views of CVGs and their opinions of mental health CVG prototypes, to help determine whether this idea warrants further investigation. Methods Pen and paper feedback forms following a brief presentation to 13–15-year-old adolescents in seven high schools (n = 207) followed by more detailed focus groups (n = 42) and workshops (n = 21) with interested students. Findings Across all three methods, participants reported playing CVGs several times a week or day to help relieve stress, feel more relaxed and relieve boredom. Most were also interested in the idea of a mental health CVG. Participants in focus groups and workshops confirmed that playing CVGs was common among themselves and their peers, and that the idea of a CVG with subtle and brief mental health content such as game-linked ‘micro messages’ was appealing. Participants recommended that the game should have an engaging interface and subtle mental health skills and information. Conclusions Findings from this exploratory study suggest that the concept of a mental health CVG appears to be appealing to adolescents. This novel approach should be tested.
A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia
Authors: Tan Yun , Wang Xiaoling , Song Huan , Zhang Yi , Zhang Rongsheng , Li Shufen , Jin Wen , Chen Saijuan , Fang Hai , Chen Zhu , Wang Kankan 
Published: August 2020

Abstract
Transcriptional deregulation initiated by oncogenic fusion proteins plays a vital role in leukemia. The prevailing view is that the oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor-α (PML/RARα), generated by the chromosome translocation t(15;17), functions as a transcriptional repressor in acute promyelocytic leukemia (APL). Here, we provide rich evidence of how PML/RARα drives oncogenesis through both repressive and activating functions, particularly the importance of the newly identified activation role for the leukemogenesis of APL. The activating function of PML/RARα is achieved by recruiting both abundant P300 and HDAC1 and by the formation of super-enhancers. All-trans retinoic acid and arsenic trioxide, 2 widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARα-regulated targets in APL cells. We use a series of in vitro and in vivo experiments to demonstrate that PML/RARα-activated target gene GFI1 is necessary for the maintenance of APL cells and that PML/RARα, likely oligomerized, transactivates GFI1 through chromatin conformation at the super-enhancer region. Finally, we profile GFI1 targets and reveal the interplay between GFI1 and PML/RARα on chromatin in coregulating target genes. Our study provides genomic insight into the dual role of fusion transcription factors in transcriptional deregulation to drive leukemia development, highlighting the importance of globally dissecting regulatory circuits.
Comparative transcriptome combined with metabolome analyses revealed key factors involved in nitric oxide (NO)-regulated cadmium stress adaptation in tall fescue
Authors: Zhu Huihui , Ai Honglian , Hu Zhengrong , Du Dongyun , Sun Jie , Chen Ke , Chen Liang 
Published: August 2020

Abstract
Background
It has been reported that nitric oxide (NO) could ameliorate cadmium (Cd) toxicity in tall fescue; however, the underlying mechanisms of NO mediated Cd detoxification are largely unknown. In this study, we investigated the possible molecular mechanisms of Cd detoxification process by comparative transcriptomic and metabolomic approaches.

Results
The application of Sodium nitroprusside (SNP) as NO donor decreased the Cd content of tall fescue by 11% under Cd stress (T1 treatment), but the Cd content was increased by 24% when treated with Carboxy-PTIO (c-PTIO) together with Nitro-L-arginine methyl ester (L-NAME) (T2 treatment). RNA-seq analysis revealed that 904 (414 up- and 490 down-regulated) and 118 (74 up- and 44 down-regulated) DEGs were identified in the T1 vs Cd (only Cd treatment) and T2 vs Cd comparisons, respectively. Moreover, metabolite profile analysis showed that 99 (65 up- and 34-down- regulated) and 131 (45 up- and 86 down-regulated) metabolites were altered in the T1 vs Cd and T2 vs Cd comparisons, respectively. The integrated analyses of transcriptomic and metabolic data showed that 81 DEGs and 15 differentially expressed metabolites were involved in 20 NO-induced pathways. The dominant pathways were antioxidant activities such as glutathione metabolism, arginine and proline metabolism, secondary metabolites such as flavone and flavonol biosynthesis and phenylpropanoid biosynthesis, ABC transporters, and nitrogen metabolism.

Conclusions
In general, the results revealed that there are three major mechanisms involved in NO-mediated Cd detoxification in tall fescue, including (a) antioxidant capacity enhancement; (b) accumulation of secondary metabolites related to cadmium chelation and sequestration; and (c) regulation of cadmium ion transportation, such as ABC transporter activation. In conclusion, this study provides new insights into the NO-mediated cadmium stress response.