bluuebunny/crossref_metadata_2025_split huggingface dataset:
PmiREN: a comprehensive encyclopedia of plant miRNAs
Authors: Guo Zhonglong , Kuang Zheng , Wang Ying , Zhao Yongxin , Tao Yihan , Cheng Chen , Yang Jing , Lu Xiayang , Hao Chen , Wang Tianxin , Cao Xiaoyan , Wei Jianhua , Li Lei , Yang Xiaozeng 
Published: October 2019

Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that function as diverse endogenous gene regulators at the post-transcriptional level. In the past two decades, as research effort on miRNA identification, function and evolution has soared, so has the demand for miRNA databases. However, the current plant miRNA databases suffer from several typical drawbacks, including a lack of entries for many important species, uneven annotation standards across different species, abundant questionable entries, and limited annotation. To address these issues, we developed a knowledge-based database called Plant miRNA Encyclopedia (PmiREN, http://www.pmiren.com/), which was based on uniform processing of sequenced small RNA libraries using miRDeep-P2, followed by manual curation using newly updated plant miRNA identification criteria, and comprehensive annotation. PmiREN currently contains 16,422 high confidence novel miRNA loci in 88 plant species and 3,966 retrieved from miRBase. For every miRNA entry, information on precursor sequence, precursor secondary structure, expression pattern, clusters and synteny in the genome, potential targets supported by Parallel Analysis of RNA Ends (PARE) sequencing, and references is attached whenever possible. PmiREN is hierarchically accessible and has eight built-in search engines. We believe PmiREN is useful for plant miRNA cataloguing and data mining, therefore a resource for data-driven miRNA research in plants.
Database resources of the National Center for Biotechnology Information
Authors: Sayers Eric W , Beck Jeff , Brister J Rodney , Bolton Evan E , Canese Kathi , Comeau Donald C , Funk Kathryn , Ketter Anne , Kim Sunghwan , Kimchi Avi , Kitts Paul A , Kuznetsov Anatoliy , Lathrop Stacy , Lu Zhiyong , McGarvey Kelly , Madden Thomas L , Murphy Terence D , O’Leary Nuala , Phan Lon , Schneider Valerie A , Thibaud-Nissen Françoise , Trawick Bart W , Pruitt Kim D , Ostell James 
Published: October 2019

Abstract
The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts published in life science journals. The Entrez system provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Custom implementations of the BLAST program provide sequence-based searching of many specialized datasets. New resources released in the past year include a new PubMed interface, a sequence database search and a gene orthologs page. Additional resources that were updated in the past year include PMC, Bookshelf, My Bibliography, Assembly, RefSeq, viral genomes, the prokaryotic genome annotation pipeline, Genome Workbench, dbSNP, BLAST, Primer-BLAST, IgBLAST and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
Human RAD51 paralogue RAD51C fosters repair of alkylated DNA by interacting with the ALKBH3 demethylase
Authors: Mohan Monisha , Akula Deepa , Dhillon Arun , Goyal Arun , Anindya Roy 
Published: October 2019

Abstract
The integrity of our DNA is challenged daily by a variety of chemicals that cause DNA base alkylation. DNA alkylation repair is an essential cellular defence mechanism to prevent the cytotoxicity or mutagenesis from DNA alkylating chemicals. Human oxidative demethylase ALKBH3 is a central component of alkylation repair, especially from single-stranded DNA. However, the molecular mechanism of ALKBH3-mediated damage recognition and repair is less understood. We report that ALKBH3 has a direct protein-protein interaction with human RAD51 paralogue RAD51C. We also provide evidence that RAD51C–ALKBH3 interaction stimulates ALKBH3-mediated repair of methyl-adduct located within 3′-tailed DNA, which serves as a substrate for the RAD51 recombinase. We further show that the lack of RAD51C–ALKBH3 interaction affects ALKBH3 function in vitro and in vivo. Our data provide a molecular mechanism underlying upstream events of alkyl adduct recognition and repair by ALKBH3.
BBCancer: an expression atlas of blood-based biomarkers in the early diagnosis of cancers
Authors: Zuo Zhixiang , Hu Huanjing , Xu Qingxian , Luo Xiaotong , Peng Di , Zhu Kaiyu , Zhao Qi , Xie Yubin , Ren Jian 
Published: October 2019

Abstract
The early detection of cancer holds the key to combat and control the increasing global burden of cancer morbidity and mortality. Blood-based screenings using circulating DNAs (ctDNAs), circulating RNA (ctRNAs), circulating tumor cells (CTCs) and extracellular vesicles (EVs) have shown promising prospects in the early detection of cancer. Recent high-throughput gene expression profiling of blood samples from cancer patients has provided a valuable resource for developing new biomarkers for the early detection of cancer. However, a well-organized online repository for these blood-based high-throughput gene expression data is still not available. Here, we present BBCancer (http://bbcancer.renlab.org/), a web-accessible and comprehensive open resource for providing the expression landscape of six types of RNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), tRNA-derived fragments (tRFRNAs) and Piwi-interacting RNAs (piRNAs) in blood samples, including plasma, CTCs and EVs, from cancer patients with various cancer types. Currently, BBCancer contains expression data of the six RNA types from 5040 normal and tumor blood samples across 15 cancer types. We believe this database will serve as a powerful platform for developing blood biomarkers.
GenBank
Authors: Sayers Eric W , Cavanaugh Mark , Clark Karen , Ostell James , Pruitt Kim D , Karsch-Mizrachi Ilene 
Published: October 2019

Abstract
GenBank® (www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public database that contains over 6.25 trillion base pairs from over 1.6 billion nucleotide sequences for 450 000 formally described species. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. Recent updates include a new version of Genome Workbench that supports GenBank submissions, new submission wizards for viral genomes, enhancements to BankIt and improved handling of taxonomy for sequences from pathogens.
Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: a systematic review
Authors: Cruz Bruna C S , Sarandy Mariáurea M , Messias Anny C , Gonçalves Reggiani V , Ferreira Célia L L F , Peluzio Maria C G 
Published: October 2019

Abstract

Context
Recent evidence suggests that modulation of the gut microbiota may help prevent colorectal cancer.

Objective
The aim of this systematic review was to investigate the role of probiotics and synbiotics in the prevention of colorectal cancer and to clarify potential mechanisms involved.

Data Sources
The PubMed, ScienceDirect, and LILACS databases were searched for studies conducted in humans or animal models and published up to August 15, 2018.

Study Selection
Clinical trials and placebo-controlled experimental studies that evaluated the effects of probiotics and synbiotics in colorectal cancer and cancer associated with inflammatory bowel disease were included. Of 247 articles identified, 31 remained after exclusion criteria were applied. A search of reference lists identified 5 additional studies, for a total of 36 included studies.

Data Extraction
Two authors independently assessed risk of bias of included studies and extracted data. Data were pooled by type of study, ie, preclinical or clinical.

Results
The results showed positive effects of probiotics and synbiotics in preventing colorectal cancer. The main mechanisms identified were alterations in the composition and metabolic activity of the intestinal microbiota; reduction of inflammation; induction of apoptosis and inhibition of tumor growth; modulation of immune responses and cell proliferation; enhanced function of the intestinal barrier; production of compounds with anticarcinogenic activity; and modulation of oxidative stress.

Conclusions
Probiotics or synbiotics may help prevent colorectal cancer, but additional studies in humans are required to better inform clinical practice.
A provincial assessment of readiness for paediatric emergencies: What are the existing resource gaps in Alberta?
Authors: Stys Dana , Landry Kerri , Mitra Tatum , Grant Vincent 
Published: October 2019

Abstract

Objectives
A large proportion of all emergency visits for paediatric patients across Canada are to general emergency departments (EDs). These centres may not be adequately equipped to provide optimal care for high acuity paediatric emergencies. The objective of this study was to determine paediatric readiness for general EDs and urgent care centres (UCCs) across Alberta and provide each centre with an overall weighted Paediatric Readiness Score (WPRS).

Methods
A paediatric readiness assessment consisting of 55-questions normalized on a 100-point scale was used to survey 107 general EDs, UCCs, and tertiary paediatric EDs in Alberta, Canada. It addresses six primary categories, including Coordination of Patient Care, Physician/Nurse Staffing and Training, Quality Improvement Activities, Patient Safety Initiatives, Policies and Procedures, and Equipment and Supplies. Descriptive statistics were used to present the WPRS score among different groups. Linear regression models were used to explore factors associated with the score.

Results
The overall response rate was 59.8%. The median overall WPRS (/100) for all general EDs and UCCs was 48.4 ([interquartile range {IQR}] 17.6). Factors that were correlated with overall score included high paediatric patient volume (24.28, 95% confidence interval [CI]: 10.52 to 38.04) and involvement in a simulation education outreach program (9.38, 95% CI: 1.11 to 17.66).

Conclusion
Based on this survey, the WPRS of EDs and UCCs across Alberta suggest a need to improve readiness to respond to high acuity paediatric emergencies in these settings.
Type 2 Diabetes Affects Joint Pain Severity in People with Localized Osteoarthritis: A Retrospective Study
Authors: Alenazi Aqeel M , Obaidat Sakher M , Alshehri Mohammed M , Alothman Shaima , Gray Corey , Rucker Jason , Waitman Lemuel R , Kluding Patricia M 
Published: October 2019

Abstract

Objective
To examine the association between type 2 diabetes (T2D) and pain severity in people with localized osteoarthritis (OA) and to explore the association between glycemic control, measured by hemoglobin A1c (HbA1c) level, and pain severity in people with localized OA and T2D.

Design
Retrospective study.

Setting
A tertiary medical center.

Subjects
Data from 819 patients (mean age = 65.08±9.77 years, 54.3% women) were used.

Methods
Patients were grouped to localized OA only (N = 671) and localized OA+T2D (N = 148) based on diagnosis codes. An index date was set as the first diagnosis date of localized OA and linked to pain severity, measured by numeric rating scale from 0 to 10. HbA1c values were obtained for patients with T2D within six months of the index date. Multiple linear regression was used.

Results
After controlling for age, gender, body mass index (BMI); diagnoses of depression, hypertension, dyslipidemia; OA locations; and medication list (+/- 90 days of the index date), T2D was significantly associated with increased pain severity (B = 1.07, 95% confidence interval [CI] = 0.25 to 1.88, P = 0.014). For patients with T2D and localized OA with available data for HbA1c (N = 87), the results showed that an increased HbA1c value was significantly associated with higher pain severity (B = 0.36, 95% CI = 0.036 to 0.67, P = 0.029) after controlling for age, gender, BMI, medications, and OA locations.

Conclusion
T2D was associated with higher pain severity in people with localized OA, and poor glycemic control was associated with higher pain severity in people with localized OA+T2D. Clinicians should emphasize that better HbA1c control might help with pain management in people with T2D and OA.
Providing Value in Fracture Care: Academic Versus Private Setting
Authors: Lundy Douglas W. , Jahangir A. Alex 
Published: October 2019

Summary:
Although the science of fracture care transcends the setting, the delivery of value may be dramatically different depending on the practice situation. Compared to our colleagues specializing in total joint arthroplasty, trauma surgeons have a greater challenge demonstrating increased quality relative to the cost of care. Although most orthopedic surgeons are in private practice, their individual practice settings vary significantly. Generally speaking, private groups with dynamic and forward-thinking leadership can seize opportunity to increase value in fracture care, and nimble action can improve value for the patient and the practice. Academic medical centers have synergies to enhance integrated medical care, and the tripartite mission of education, research and patient care lend themselves to increasing value. In either setting, leadership in orthopedic surgery can enhance value in fracture care.
Value Denominator: The Fundamentals of Costing for Orthopaedic Surgeons
Authors: Parikh Harsh R. , O'Hara Nathan , Levy Joseph F. , Cunningham Brian P. 
Published: October 2019

Summary:In any discipline, improving quality and efficiency of services acts as a unifying goal. In health care, the goal of achieving high-value care is the new doctrine for all individual entities: payors, providers, and patients. Value is defined as the ratio of outcomes to costs incurred. Therefore, a strong understanding and interpretation of cost measures is crucial to accurately deriving health care value. Health care costing is not simply limited to the costs of implants or the procedure but the costs required to deliver treatment throughout the episode of care. Consequently, physicians serve a keystone role toward driving change in health care costs and initiate high-value care practices. However, physicians require a better understanding of health care costs and institutional accounting practices. To this effort, it is critical that health care providers begin to close the knowledge gap around health care costing and provide leadership when advocating for high-value patient care. This review is purposed to provide a basic review of fundamental components for health care economics, deciphering health care costing, and preview current strategies that prioritize high-value patient care.
Does Value Matter in Orthopaedic Trauma?: A Survey of Orthopaedic Trauma Association Members
Authors: Gorman Tiffany L. , S. Albersheim Melissa , Parikh Harsh R. , Flagstad Ilexa R. , Okelana A. Bandele , Vang Sandy , Johal Herman , Cunningham Brian P. 
Published: October 2019

Objectives:
With value-based payment models on the horizon, this study was designed to examine the perceptions of value-based care among orthopaedic traumatologists and how they influence their practice.

Design:
Systems-based survey study.

Setting:
Orthopaedic Trauma Association (OTA) research surveys.

Participants:
OTA members.

Main Outcome Measure:
Thirty-eight–question surveys focusing on 5 areas related to value-based care: understanding value, assessing interest, barriers, perceptions around implementing value-based strategies, and policy.

Results:
Of 1106 OTA members, 252 members responded for a response rate of 22.7%. Consideration around cost was not different between hospital, academic, and private practice settings (P = 0.47). Previous reported experience in finance increased the amount surgical decision-making was influenced by cost (P < 0.01), along with reported understanding of implant costs (P < 0.01). Over half of the respondents (59.4%) believed value-based payments are coming to orthopaedic trauma. The vast majority (88.5%) believed bundled payments would be unsuccessful or only partially successful. With respect to barriers, a third of respondents (34.7%) indicated accurate cost data prevented the implementation of programs that track and maximize value, another third (31.5%) attributed it to a limited ability to collect patient-reported outcomes, and the rest (33.8%) were split between lack of institutional interest and access to funding.

Conclusion:
Our study indicated the understanding of value in orthopaedic trauma is limited and practice integration is rare. Reported experience in finance was the only factor associated with increased consideration of value-based care in practice. Our results highlight the need for increased exposure and resources to changing health care policy, specifically for orthopaedic traumatologists.

Level of Evidence:
Level V. See Instructions for Authors for a complete description of levels of evidence.
Variation in Implant Selection for Ankle Fractures: Identifying Cost Drivers
Authors: Okelana A. Bandele , McMillan Logan J. , Kibble Kendra , Parikh Harsh R. , Gorman Catlea , Schaefbauer Heather , Cunningham Brian P. 
Published: October 2019

Background:
Implant selection is the first opportunity for surgeons to control costs of fracture fixation. The current literature has demonstrated surgeons' poor understanding of implant costs. Our study evaluated implant cost variability for surgically treated ankle fractures and distal tibia fractures. Our hypothesis was that significant cost variation exists among providers. The goal was to identify cost drivers and determine whether specialty training is linked to implant selection.

Methods:
A retrospective 2010–2017 chart review was performed for 1281 patients at a Level I trauma center. Patients were excluded for skeletal immaturity, open fractures, polytrauma, and concurrent surgeries. Variables were assessed included age, sex, body mass index, OTA/AO classification, Weber classification, 1-year reoperation status, surgeon specialty, and use of syndesmotic screws, locking plates, and cannulated screws. Construct cost was determined by using electronic medical record implant model numbers cross-referenced with the chargemaster database. Statistical analysis involved intergroup comparative tests, regression analysis, and goodness-of-fit analyses.

Results:
Implant cost was different among OTA patterns (P < 0.01), highest among 43C ($3771) and lowest with 44A ($819). Construct costs of OTA 43 fractures varied from $2568 to 3771, whereas OTA 44 ranged from $819 to $1474. Costs were comparable across Weber patterns (P = 0.15), with Weber B having the highest ($1494). Costs were highest among reconstructive, podiatry, and spine surgeons, with mean costs of $1804, $1404, and $1396, respectively. Traumatologist constructs had the lowest overall price ($987). A total of 433 (33.8%) procedures used locking plates with 512 (40.0%) using at least one cannulated screw. Locking plates averaged a larger total implant cost ($1947) than nonlocking plates ($1313) but had a comparable reoperation rate (18.5% vs. 17.7%, P = 0.81). Use of a cannulated screw presented a higher total cost ($2008 vs. $1435) with comparable reoperation rates (17.4% vs. 18.8%, P = 0.72). A total of 401 (31.5%) patients received syndesmotic fixation and a significantly higher reoperation rate (17.0% vs. 11.0%, P < 0.01). Overall, 199 patients underwent elective hardware removal, 23 were infected, 7 required revision, and 3 were identified with a nonunion.

Conclusions:
Our study demonstrated significant variability in implant costs for ankle fracture fixation and identified the key cost drivers as locking plates and cannulated screws. Surgical management of ankle fractures could be an ideal setting to pilot economic alignment between physicians and hospitals to drive value.

Level of Evidence:
Level III. Retrospective Cohort.
Treatment Failures of Direct Oral Anticoagulants
Authors: Kajy Marvin , Mathew Anil , Ramappa Preeti 
Published: October 2019

Background:
Use of direct oral anticoagulants (DOACs) has increased over the years, because they have become a safe and effective alternative to the Vitamin-K antagonists in various clinical scenarios. With their increased use, reports have emerged describing their failure.

Study Question:
What are the patient characteristics and clinical settings in which DOAC treatment failure manifests?

Data Sources:
We searched published reports in Google Scholar, PubMed, MEDLINE, and Embase from the introduction of DOACs in any therapy until March 2019.

Study Design:
Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. Primary endpoints were new thrombus formation, failure of resolution of an existing thrombus, or discovery of subtherapeutic drug level. Other endpoints were time to treatment failure, manifestations of treatment failure, and new treatment after DOAC failure.

Results:
Our search yielded 51 manuscripts, describing 79 patients who exhibited DOAC failure. The most common treatment failures were in patients with antiphospholipid syndrome (44.3%), atrial fibrillation (30.4%), and deep venous thrombosis (6.3%). There was a trend toward higher failure rate for rivaroxaban (65.8%) followed by dabigatran (27.8%), apixaban (7.6%), and then edoxaban (1.3%). Each agent had different median failure times. Most common manifestations of treatment failure were stroke/transient ischemic attack (20.3%), pulmonary embolism (19.0%), and deep venous thrombosis (19.0%). More than half of patients were transitioned to a Vitamin-K antagonist after DOAC failure (55.7%).

Conclusions:
Our analysis illustrates that DOACs may fail in the setting of Food and Drug Administration and non–Food and Drug Administration- approved indications. In clinical practice, it may be best to choose between available anticoagulant drugs on a case-by-case basis.
Role of CRF receptor 1 antagonism in the bed nucleus of the stria terminalis of male rats after intermittent social defeat stress
Authors: Vasconcelos Mailton , Stein Dirson J. , Gallas-Lopes Matheus , Landau Luane , Behrens Luiza , Albrechet-Souza Lucas , Miczek Klaus A. , de Almeida Rosa Maria M. 
Published: October 2019

AbstractWe recently demonstrated that the experience of brief episodes of social defeat caused impairments in social behaviors. Moreover, we provided evidence that the antagonism of corticotropin-releasing factor binding protein (CRFBP) in the bed nucleus of the stria terminalis (BNST) restored social approach in stressed animals. This study aimed to test the relation between corticotropin-releasing factor receptor type 1 (CRFR1) located in the BNST and the establishment of social stress-disrupted behaviors in rats submitted to social defeat in the resident-intruder paradigm. Animals were tested for sweet solution preference, subjected to the elevated-plus maze (EPM), and to the social interaction three-chamber test. Social behavior was tested after BNST drug infusions. The drug used in this study was a CRF receptor 1 antagonist, CP376395 (CP), administered in two doses: 50 ng/0.20 μL/side, and 500 ng/0.20 μL/side. Saline solution was used as vehicle and administered 0.20 μL/side. Socially stressed animals (n = 11) did not differ compared to control animals (n = 11) in the EPM. Stressed animals displayed impaired social behavior, represented by a decrease in time spent in the interaction zone. The lower dose (CP 50 ng/0.20 μL/side) administered intra-BNST restored social behaviors in stressed animals. On the other hand, the higher dose of the CRFR1 antagonist (CP 500 ng/0.20 μL/side) induced social avoidance in rats without a history of agonistic confrontations. These findings implicate BNST CRFR1 signaling in the modulation of social behaviors in rats given the choice to explore an unfamiliar conspecific.