bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divalent cations promote TALE DNA-binding specificity
Authors: Cuculis Luke , Zhao Chuankai , Abil Zhanar , Zhao Huimin , Shukla Diwakar , Schroeder Charles M 
Published: December 2019

AbstractRecent advances in gene editing have been enabled by programmable nucleases such as transcription activator-like effector nucleases (TALENs) and CRISPR–Cas9. However, several open questions remain regarding the molecular machinery in these systems, including fundamental search and binding behavior as well as role of off-target binding and specificity. In order to achieve efficient and specific cleavage at target sites, a high degree of target site discrimination must be demonstrated for gene editing applications. In this work, we studied the binding affinity and specificity for a series of TALE proteins under a variety of solution conditions using in vitro fluorescence methods and molecular dynamics (MD) simulations. Remarkably, we identified that TALEs demonstrate high sequence specificity only upon addition of small amounts of certain divalent cations (Mg2+, Ca2+). However, under purely monovalent salt conditions (K+, Na+), TALEs bind to specific and non-specific DNA with nearly equal affinity. Divalent cations preferentially bind to DNA over monovalent cations, which attenuates non-specific interactions between TALEs and DNA and further stabilizes specific interactions. Overall, these results uncover new mechanistic insights into the binding action of TALEs and further provide potential avenues for engineering and application of TALE- or TALEN-based systems for genome editing and regulation.
Omics Playground: a comprehensive self-service platform for visualization, analytics and exploration of Big Omics Data
Authors: Akhmedov Murodzhon , Martinelli Axel , Geiger Roger , Kwee Ivo 
Published: December 2019

Abstract
As the cost of sequencing drops rapidly, the amount of ‘omics data increases exponentially, making data visualization and interpretation—‘tertiary‘ analysis a bottleneck. Specialized analytical tools requiring technical expertise are available. However, consolidated and multi-faceted tools that are easy to use for life scientists is highly needed and currently lacking. Here we present Omics Playground, a user-friendly and interactive self-service bioinformatics platform for the in-depth analysis, visualization and interpretation of transcriptomics and proteomics data. It provides a large number of different tools in which special attention has been paid to single cell data. With Omics Playground, life scientists can easily perform complex data analysis and visualization without coding, and significantly reduce the time to discovery.
History and Correlates of Smoking Cessation Behaviors Among Smokers With Serious Mental Illness
Authors: Lubitz Su Fen , Flitter Alex , Wileyto E Paul , Ziedonis Douglas , Stevens Nathaniel , Leone Frank , Mandell David , Kimberly John , Beidas Rinad , Schnoll Robert A 
Published: December 2019

Abstract

Introduction
Individuals with serious mental illness (SMI) smoke at rates two to three times greater than the general population but are less likely to receive treatment. Increasing our understanding of correlates of smoking cessation behaviors in this group can guide intervention development.

Aims and Methods
Baseline data from an ongoing trial involving smokers with SMI (N = 482) were used to describe smoking cessation behaviors (ie, quit attempts, quit motivation, and smoking cessation treatment) and correlates of these behaviors (ie, demographics, attitudinal and systems-related variables).

Results
Forty-three percent of the sample did not report making a quit attempt in the last year, but 44% reported making one to six quit attempts; 43% and 20%, respectively, reported wanting to quit within the next 6 months or the next 30 days. Sixty-one percent used a smoking cessation medication during their quit attempt, while 13% utilized counseling. More quit attempts were associated with lower nicotine dependence and carbon monoxide and greater beliefs about the harms of smoking. Greater quit motivation was associated with lower carbon monoxide, minority race, benefits of cessation counseling, and importance of counseling within the clinic. A greater likelihood of using smoking cessation medications was associated with being female, smoking more cigarettes, and receiving smoking cessation advice. A greater likelihood of using smoking cessation counseling was associated with being male, greater academic achievement, and receiving smoking cessation advice.

Conclusions
Many smokers with SMI are engaged in efforts to quit smoking. Measures of smoking cessation behavior are associated with tobacco use indicators, beliefs about smoking, race and gender, and receiving cessation advice.

Implications
Consideration of factors related to cessation behaviors among smokers with SMI continues to be warranted, due to their high smoking rates compared to the general population. Increasing our understanding of these predictive characteristics can help promote higher engagement in evidence-based smoking cessation treatments among this subpopulation.
Resection of a Symptomatic Dysplastic Cerebellar Gangliocytoma: 2-Dimensional Operative Video
Authors: El Ahmadieh Tarek Y , Plitt Aaron R , Aoun Salah G , Patel Toral 
Published: December 2019

Abstract
Lhermitte–Duclos disease, also known as dysplastic cerebellar gangliocytoma, is a rare benign cerebellar tumor that is typically observed but may occasionally become symptomatic and requires surgical intervention. The condition is caused by a mutation in the phosphatase and tensin homolog (PTEN) gene, which results in dysregulation of the mammalian target of rapamycin pathway. A germline PTEN mutation results in multi-organ involvement and is termed Cowden syndrome. There is a scarcity of surgical videos in the published literature that demonstrate an intraoperative resection of this lesion and illustrate the pathology in Vivo. We present an operative video of a surgical resection of a symptomatic dysplastic cerebellar gangliocytoma in a 44-yr-old male patient who presented with a 3-mo history of progressive headaches and hydrocephalus. The patient underwent an endoscopic third ventriculostomy and, subsequently, a right suboccipital craniotomy for microsurgical resection of the mass. The procedure was performed with the patient in the lateral position. The microscope was positioned at the head of the bed and the stereotaxic system monitor on the patient's left side. The patient tolerated the procedure well and imaging obtained at 18 mo was negative for residual or recurrent disease. The patient gave written consent for video recording as part of the surgery informed consent. No identifiable images or video footage of the face are shown, and institutional review board approval was deemed unnecessary.
Alterations in activin A–myostatin–follistatin system associate with disease activity in inflammatory myopathies
Authors: Vernerová Lucia , Horváthová Veronika , Kropáčková Tereza , Vokurková Martina , Klein Martin , Tomčík Michal , Oreská Sabína , Špiritović Maja , Štorkánová Hana , Heřmánková Barbora , Kubínová Kateřina , Kryštůfková Olga , Mann Heřman , Ukropec Jozef , Ukropcová Barbara , Vencovský Jiří 
Published: December 2019

Abstract

Objectives
The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis.

Methods
A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR.

Results
We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = −0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls.

Conclusion
This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A–myostatin–follistatin system in muscle wasting diseases.
The effect of collaboration with top-funded scholars on scientific production
Authors: Mirnezami Seyed Reza , Beaudry Catherine , Tahmooresnejad Leila 
Published: December 2019

Abstract
The theoretical model developed in this article predicts that collaboration with top-funded scientists positively affects the number of scientific publications of an individual scientist. Having combined data on funding and publication of Quebec scientists, this article empirically tests the theoretical predictions. This article examines numerous definitions of top-funded scientists as those in the top 10 per cent, or top 5 per cent in terms of total funding, funding from the public sector, and funding from the private sector. The results show that collaborating with such top-funded scientists has a positive effect on a scientist’s number of publications, hence confirming our theoretical predictions.
What we know about research policy mix
Authors: Cocos Marta , Lepori Benedetto 
Published: December 2019

AbstractThe research policy (RP) arena has been transforming in recent years, turning into a policy mix encompassing the diversity of policy instruments embedded in, and following different policy rationales and aims. Its complexity defies attempts for complex comparative analysis and eventually, a better understanding of what kind of (mixes of) funding instruments work better than others and in which situations. In this article, we address this gap by developing a conceptual framework that allows us to build the policy mix idea into the analysis of research funding instruments (RFIs), by relying on four dimensions: policy rationales, implementation modalities, policy actors, and the funding instruments interactions. We base our work on a careful literature review, especially drawing on the work of researchers who have developed similar frameworks in other policy areas, bringing it together with that of RP scholars, capturing the issues that are key to analyzing and understanding RFIs.
Dynamics of xylem and phloem sap flow in an outdoor zelkova tree visualized by magnetic resonance imaging
Authors: Terada Yasuhiko , Horikawa Yusuke , Nagata Akiyoshi , Kose Katsumi , Fukuda Kenji 
Published: December 2019

AbstractXylem and phloem sap flows in an intact, young Japanese zelkova tree (Zelkova serrata (Thunb.) Makino) growing outdoors were measured using magnetic resonance imaging (MRI). Two propagator-based sequences were developed for q-space imaging: pulse field gradient (PFG) with spin echo (PFG-SE) and stimulated echo (PFG-STE), which were used for xylem and phloem flow measurements, respectively. The data evaluation methods were improved to image fast xylem flow and slow phloem flow. Measurements were taken every 2–3 h for several consecutive days in August 2016, and diurnal changes in xylem and phloem sap flows in a cross-section of the trunk were quantified at a resolution of 1 mm2. During the day, apparent xylem flow volume exhibited a typical diurnal pattern following a vapor pressure deficit. The velocity mapping of xylem sap flow across the trunk cross section revealed that the greatest flow volume was found in current-year earlywood that had differentiated in April–May. The combined xylem flow in the 1- and 2-year-old annual rings also contributed to one-third of total sap flow. In the phloem, downward sap flow did not exhibit diurnal changes. This novel application of MRI in visualization of xylem and phloem sap flow by MRI is a promising tool for in vivo study of water transport in mature trees.
Novel Clinical Trial Designs to Improve the Efficiency of Research
Authors: Sessler Daniel I. , Myles Paul S. 
Published: December 2019

Abstract

SUMMARY
Large randomized trials provide the highest level of clinical evidence. However, enrolling large numbers of randomized patients across numerous study sites is expensive and often takes years. There will never be enough conventional clinical trials to address the important questions in medicine. Efficient alternatives to conventional randomized trials that preserve protections against bias and confounding are thus of considerable interest. A common feature of novel trial designs is that they are pragmatic and facilitate enrollment of large numbers of patients at modest cost. This article presents trial designs including cluster designs, real-time automated enrollment, and practitioner-preference approaches. Then various adaptive designs that improve trial efficiency are presented. And finally, the article discusses the advantages of embedding randomized trials within registries.
Pediatric Perioperative Mortality in Kenya
Authors: Newton Mark W. , Hurt Savannah E. , McEvoy Matthew D. , Shi Yaping , Shotwell Matthew S. , Kamau John , Nabulindo Susane , Ngumi Zipporah W. W. , Sandberg Warren S. , Sileshi Bantayehu 
Published: December 2019

Abstract

Background
The global surgery access imbalance will have a dramatic impact on the growing population of the world’s children. In regions of the world with pediatric surgery and anesthesia manpower deficits and pediatric surgery–specific infrastructure and supply chain gaps, this expanding population will present new challenges. Perioperative mortality rate is an established indicator of the quality and safety of surgical care. To establish a baseline pediatric perioperative mortality rate and factors associated with mortality in Kenya, the authors designed a prospective cohort study and measured 24-h, 48-h, and 7-day perioperative mortality.

Methods
The authors trained anesthesia providers to electronically collect 132 data elements for pediatric surgical cases in 24 government and nongovernment facilities at primary, secondary, and tertiary hospitals from January 2014 to December 2016. Data assistants tracked all patients to 7 days postoperative, even if they had been discharged. Adjusted analyses were performed to compare mortality among different hospital levels after adjusting for prespecified risk factors.

Results
Of 6,005 cases analyzed, there were 46 (0.8%) 24-h, 62 (1.1%) 48-h, and 77 (1.7%) 7-day cumulative mortalities reported. In the adjusted analysis, factors associated with a statistically significant increase in 7-day mortality were American Society of Anesthesiologists Physical Status of III or more, night or weekend surgery, and not having the Safe Surgery Checklist performed. The 7-day perioperative mortality rate is less in the secondary (1.4%) and tertiary (2.4%) hospitals when compared with the primary (3.7%) hospitals.

Conclusions
The authors have established a baseline pediatric perioperative mortality rate that is greater than 100 times higher than in high-income countries. The authors have identified factors associated with an increased mortality, such as not using the Safe Surgery Checklist. This analysis may be helpful in establishing pediatric surgical care systems in low–middle income countries and develop research pathways addressing interventions that will assist in decreasing mortality rate.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy
Authors: Albright Benjamin B. , Shorter Jade M. , Mastroyannis Spyridon A. , Ko Emily M. , Schreiber Courtney A. , Sonalkar Sarita 
Published: December 2019

OBJECTIVE:To estimate the incidence of gestational trophoblastic neoplasia following complete and partial molar pregnancy after reaching normal human chorionic gonadotropin (hCG) levels to guide evidence-based follow-up recommendations.DATA SOURCES:MEDLINE, EMBASE, Web of Science, POPLINE, Cochrane, and ClinicalTrials.gov were searched from inception to November 2018, using the intersection of “gestational trophoblastic disease,” “molar pregnancy,” and “human chorionic gonadotropin” themes.METHODS OF STUDY SELECTION:Search results were screened to identify cohort studies of molar pregnancy reporting gestational trophoblastic neoplasia development, with at least 6 months of intended normal hCG follow-up.TABULATION, INTEGRATION, AND RESULTS:Two reviewers independently identified articles for inclusion. Data were extracted using a standardized form. For meta-analysis, cumulative incidence of gestational trophoblastic neoplasia, with CIs by the Agresti-Coull method, and pooled risk ratios (RRs) comparing complete and partial mole were calculated. Among the 19 eligible studies that reported adequate data for inclusion in the primary meta-analysis, we found low incidence of gestational trophoblastic neoplasia after normal hCG level following both complete mole (64/18,357, 0.35%, 95% CI 0.27–0.45%), and partial mole (5/14,864, 0.03%, 95% CI 0.01–0.08%). There was a significantly higher risk of gestational trophoblastic neoplasia after complete compared with partial molar pregnancy (RR 4.72, 95% CI 1.81–12.3,P=.002). Among gestational trophoblastic neoplasia cases after normal hCG level following complete mole, 89.6% occurred when the time from evacuation to normalization was 56 days or longer, and 60.7% were diagnosed beyond the commonly recommended 6-month surveillance interval. Sensitivity analyses, including those limiting to studies at low risk of bias, did not significantly affect results. We found an overall incidence of gestational trophoblastic neoplasia of 15.7% for complete mole (1,354/8,611, 95% CI 15.0–16.5%) and 3.95% for partial mole (221/5,593, 95% CI 3.47–4.50%).CONCLUSION:Gestational trophoblastic neoplasia development after normal hCG level following molar pregnancy is rare. Recommendations for frequency and duration of hCG follow-up can be minimized to lessen burden on patients and informed by the type of molar pregnancy and time interval from uterine evacuation to hCG normalization.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42019116414.
Understanding the Radiographic Anatomy of the Proximal Ulna and Avoiding Inadvertent Intraarticular Screw Placement
Authors: Githens Thomas C. , Campbell Sean T. , Salazar Brett , Goodnough L. Henry , DeBaun Malcolm R. , Bishop Julius A. , Gardner Michael J. 
Published: December 2019

Objectives:
To map the proximal ulnar articular margins and ensure safe extraarticular placement of implants.

Methods:
Ten fresh frozen adult elbow cadaver specimens were obtained. Radiopaque wire was applied to the articular margin of the articular facets and the central trochlear ridge of the proximal ulna. Fluoroscopic images were obtained demonstrating the articular facet margins. Radiographic measurements were performed and used to identify relative safe screw zones.

Results:
All specimens demonstrated marked extension of the ulnar and radial facets dorsal to the central trochlear ridge. The dorsal extent of the ulnar facets from the central trochlear ridge averaged 9.7 mm (range, 7.9–13 mm; SD, 1.5 mm) and 6.2 mm (range, 3.4–9.4 mm; SD, 1.9 mm), respectively. The average footprint of the posterior ulnar facet occupied 44% (±4.9%) of the total ulnar height from the dorsal cortex to the trochlear ridge.

Conclusions:
The articular margins of the anterior and posterior facets of the proximal ulna are challenging to identify radiographically. A surgical “at-risk zone” exists within 9.7 mm from the radiographic margin of the central trochlear ridge. Implants placed within this zone have the potential to violate the articular surface.
Function Preservation or Oncological Appropriateness in Spinal Bone Tumors?
Authors: Girolami Marco , Boriani Stefano , Ghermandi Riccardo , Bandiera Stefano , Barbanti-Brodano Giovanni , Terzi Silvia , Tedesco Giuseppe , Evangelisti Gisberto , Pipola Valerio , Ricci Alessandro , Cecchinato Riccardo , Gasbarrini Alessandro 
Published: December 2019

Study Design.
Retrospective review of prospectively collected data.

Objective.
To evaluate (1) if the segmental resection of the content of the spinal canal could provide an Enneking appropriate tumor-free margin for local control of primary bone tumors surrounding and invading the canal and (2) the safety profile of the segmental resection of the neurostructures.

Summary of Background Data.
Treatment outcomes of primary malignant and benign aggressive bone tumors of the spine have been dramatically changed by the application of the musculoskeletal oncologic principles described by Enneking. However, the efficacy of spinal oncology surgery might be limited by unique features of spinal anatomy.

Methods.
Database search was conducted with the following inclusion criteria: en bloc resection, segmental inclusion of the spinal canal content in the surgical specimen, histologically proven diagnosis, minimum follow-up of 2 years. Exclusion criteria were piecemeal excision of the tumor (debulking) and diagnosis other than primary bone tumors (metastasis, or local extension of extraosseous tumors).

Results.
A consecutive cohort of eight patients (three men, five women) was available for review. Two patients died within 3 months from the surgery for systemic disease progression or sequelae of the surgery. En bloc resection with segmental spinal canal content inclusion was able to achieve local control of the disease in four out of remaining six cases (66.7%) at an average follow-up of 68.7 months (range 12–174 mo). Three patients in whom local control was achieved are free from disease at an average follow-up of 98.7 months (range 38–174), and one died for systemic disease progression (after 38 mo). Seven out of 8 patients (87.5%) experienced overall 16 complications.

Conclusion.
En bloc resection including the spinal canal content (spinal amputation) to achieve a tumor-free margin might be considered to perform an Enneking appropriate treatment for motivated patients.

Level of Evidence: 4