bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative, super-resolution localization of small RNAs with sRNA-PAINT
Authors: Huang Kun , Demirci Feray , Batish Mona , Treible Wayne , Meyers Blake C , Caplan Jeffrey L 
Published: July 2020

AbstractSmall RNAs are non-coding RNAs that play important roles in the lives of both animals and plants. They are 21- to 24-nt in length and ∼10 nm in size. Their small size and high diversity have made it challenging to develop detection methods that have sufficient resolution and specificity to multiplex and quantify. We created a method, sRNA-PAINT, for the detection of small RNAs with 20 nm resolution by combining the super-resolution method, DNA-based points accumulation in nanoscale topography (DNA-PAINT), and the specificity of locked nucleic acid (LNA) probes for the in situ detection of multiple small RNAs. The method relies on designing probes to target small RNAs that combine DNA oligonucleotides (oligos) for PAINT with LNA-containing oligos for hybridization; therefore, we developed an online tool called ‘Vetting & Analysis of RNA for in situ Hybridization probes’ (VARNISH) for probe design. Our method utilizes advances in DNA-PAINT methodologies, including qPAINT for quantification, and Exchange-PAINT for multiplexing. We demonstrated these capabilities of sRNA-PAINT by detecting and quantifying small RNAs in different cell layers of early developmental stage maize anthers that are important for male sexual reproduction.
CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design
Authors: Jaeckle Kurt A , Ballman Karla V , van den Bent Martin , Giannini Caterina , Galanis Evanthia , Brown Paul D , Jenkins Robert B , Cairncross J Gregory , Wick Wolfgang , Weller Michael , Aldape Kenneth D , Dixon Jesse G , Anderson S Keith , Cerhan Jane H , Wefel Jeffrey S , Klein Martin , Grossman Stuart A , Schiff David , Raizer Jeffrey J , Dhermain Frederick , Nordstrom Donald G , Flynn Patrick J , Vogelbaum Michael A 
Published: July 2020

Abstract

Background
We report the analysis involving patients treated on the initial CODEL design.

Methods
Adults (&gt;18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm.

Results
Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months.

Conclusions
TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.
Improved catalytic activity and stability of cellobiohydrolase (Cel6A) from the Aspergillus fumigatus by rational design
Authors: Dodda Subba Reddy , Sarkar Nibedita , Jain Piyush , Aikat Kaustav , Mukhopadhyay Sudit S 
Published: July 2020

Abstract
Cheap production of glucose is the current challenge for the production of cheap bioethanol. Ideal protein engineering approaches are required for improving the efficiency of the members of the cellulase, the enzyme complex involved in the saccharification process of cellulose. An attempt was made to improve the efficiency of the cellobiohydrolase (Cel6A), the important member of the cellulase isolated from Aspergillus fumigatus (AfCel6A). Structure-based variants of AfCel6A were designed. Amino acids surrounding the catalytic site and conserved residues in the cellulose-binding domain were targeted (N449V, N168G, Y50W and W24YW32Y). I mutant 3 server was used to identify the potential variants based on the free energy values (∆∆G). In silico structural analyses and molecular dynamics simulations evaluated the potentiality of the variants for increasing thermostability and catalytic activity of Cel6A. Further enzyme studies with purified protein identified the N449V is highly thermo stable (60°C) and pH tolerant (pH 5–7). Kinetic studies with Avicel determined that substrate affinity of N449V (Km =0.90 ± 0.02) is higher than the wild type (1.17 ± 0.04) and the catalytic efficiency (Kcat/Km) of N449V is ~2-fold higher than wild type. All these results suggested that our strategy for the development of recombinant enzyme is a right approach for protein engineering.
Does Option Trading Have a Pervasive Impact on Underlying Stock Prices?
Authors: Ni Sophie X , Pearson Neil D , Poteshman Allen M , White Joshua 
Published: July 2020

Abstract
The question of whether and to what extent option trading affects underlying stock prices has been of interest to researchers since exchange-based options trading began in 1973. Recent research presents evidence of an informational channel through which option trading affects stock prices by showing that option market makers’ stock trades to hedge new options positions cause the information reflected in option trading to be impounded into underlying equity prices. This paper provides evidence of a noninformational channel through which option market maker hedge rebalancing affects stock return volatility and the probability of large stock price moves.
PKM2-dependent glycolysis promotes skeletal muscle cell pyroptosis by activating the NLRP3 inflammasome in dermatomyositis/polymyositis
Authors: Liu Di , Xiao Yizhi , Zhou Bin , Gao Siming , Li Liya , Zhao Lijuan , Chen Weilin , Dai Bingying , Li Qiuxiang , Duan Huiqian , Zuo Xiaoxia , Luo Hui , Zhu Honglin 
Published: July 2020

Abstract

Objectives
Muscle cell necrosis is the most common pathological manifestation of idiopathic inflammatory myopathies. Evidence suggests that glycolysis might participate in it. However, the mechanism is unclear. This study aimed to determine the role of glycolysis in the muscle damage that occurs in DM/PM.

Methods
Mass spectrometry was performed on muscle lesions from DM/PM and control subjects. The expression levels of pyruvate kinase isozyme M2 (PKM2), the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis-related genes in muscle tissues or plasma were determined by real-time PCR, western blot analysis, IF and ELISA. In addition, IFNγ was used to stimulate myotubes, and the relationships among PMK2 expression, NLRP3 inflammasome activation and pyroptosis were investigated.

Results
Mass spectrometry and bioinformatics analysis suggested that multiple glycolysis processes, the NLRP3 inflammasome and programmed cell death pathway-related proteins were dysregulated in the muscle tissues of DM/PM. PKM2 and the NLRP3 inflammasome were upregulated and positively correlated in the muscle fibres of DM/PM. Moreover, the pyroptosis-related proteins were increased in muscle tissues of DM/PM and were further increased in PM. The levels of PKM2 in muscle tissues and IL-1β in plasma were high in patients with anti-signal recognition particle autoantibody expression. The pharmacological inhibition of PKM2 in IFNγ-stimulated myotubes attenuated NLRP3 inflammasome activation and subsequently inhibited pyroptosis.

Conclusion
Our study revealed upregulated glycolysis in the lesioned muscle tissues of DM/PM, which activated the NLRP3 inflammasome and leaded to pyroptosis in muscle cells. The levels of PKM2 and IL-1β were high in patients with anti-signal recognition particle autoantibody expression. These proteins might be used as new biomarkers for muscle damage.
The Use of Psychological Patient Reported Outcome Measures to Identify Adolescent Athletes at Risk for Prolonged Recovery Following an ACL Reconstruction
Authors: Ellis Henry B. , Sabatino Meagan , Nwelue Emmanuel , Wagner K. John , Force Erica , Wilson Philip 
Published: July 2020

Background:
Psychological response to injury and the recovery process impact return to play and can put an athlete at risk for prolonged recovery. The purpose of this study was to investigate the psychological changes that occur surrounding an anterior cruciate ligament (ACL) reconstruction utilizing a set of patient reported outcomes measures (PROMs) that focus on psychological factors.

Methods:
Consecutive patients undergoing a primary ACL reconstruction, ages 12 to 18, were recruited. Patients were included if they verbalized a desire to return to the same sport and a baseline Tegner of >6. Functional and psychological PROMs were administered preoperatively, 6 months, and 1 year postoperatively. A Y-Balance Test was utilized to assess for clearance.

Results:
Of the 68 participants, 36 were female (52.9%) and 32 male, with a mean age of 14.5 years. On average, participants were cleared to return to sport 259.1 days postoperatively. Of the measures given preoperatively, only the Athletic Coping Skills Inventory-28 (ACSI)-28 correlated with delayed recovery time (r
s=−0.291, P=0.04). Lower baseline ACSI-28 subscale scores in coachability (r
s=−0.298, P=0.03) and Coping with Adversity (r
s=−0.341, P=0.01) were correlated with delayed recovery. Participants that took longer than average to recover scored significantly lower on the ACSI-28 preoperatively than those with a shorter recovery time (62.04 vs. 54.8, P<0.01). Participants that scored <58 on their preoperative ACSI-28 took 2 months longer to recover than participants who scored ≥58 (9.6 vs. 7.65 mo, P<0.01). At 6 months postoperatively, higher ACSI-28 subscale Concentration (r
s=−0.357, P<0.01) and Peaking Under Pressure (r
s=−0.274, P=0.04) scores correlated with shorter recovery time.

Conclusions:
The ACSI-28 significantly correlated with recovery time following ACL reconstruction. A baseline score of 58 may be a valuable cutoff to identify youth athletes at risk for prolonged recovery.

Level of Evidence:
Level II—prospective study.
Targeting microRNA in hematologic malignancies
Authors: Han Zhen , Rosen Steven T. , Querfeld Christiane 
Published: July 2020

Purpose of review
MiRNAs are critical regulators for gene expression. Numerous studies have revealed how miRNAs contribute to the pathogenesis of hematologic malignancies.

Recent findings
The identification of novel miRNA regulatory factors and pathways crucial for miRNA dysregulation has been linked to hematologic malignancies. miRNA expression profiling has shown their potential to predict outcomes and treatment responses. Recently, targeting miRNA biogenesis or pathways has become a promising therapeutic strategy with recent miRNA-therapeutics being developed.

Summary
We provide a comprehensive overview of the role of miRNAs for diagnosis, prognosis, and therapeutic potential in hematologic malignancies.
A digital health psychological intervention (WebMAP Mobile) for children and adolescents with chronic pain: results of a hybrid effectiveness-implementation stepped-wedge cluster randomized trial
Authors: Palermo Tonya M. , de la Vega Rocio , Murray Caitlin , Law Emily , Zhou Chuan 
Published: July 2020

Abstract
Although psychological treatments benefit youth with chronic pain, treatment is not accessible in most communities. Digital health interventions offer promise for expanding access and reach to this population. Using a stepped-wedge cluster randomized trial design, we evaluated effectiveness and implementation of a digital health delivered psychological intervention for pediatric chronic pain. One hundred forty-three youth, aged 10 to 17 years, with chronic pain and a caregiver were recruited from 8 clinics in the United States. Active intervention included access to the Web-based Management of Adolescent Pain (WebMAP) Mobile app and the WebMAP parent web site to learn pain self-management skills. Effectiveness outcomes included pain intensity, disability, and patient global impression of change, while Reach, Adoption, Implementation, and Maintenance were implementation outcomes. Results showed that youth in both treatment conditions (WebMAP vs Usual Care) had similar changes over time in pain and disability. Youth in the WebMAP condition perceived greater improvement (patient global impression of change) at post-treatment and follow-up (d's = 0.54 and 0.44, P < 0.05) compared with youth receiving usual care. Use of the digital health intervention was modest and variable; approximately 30% of youth and parents completed treatment. Greater engagement (number of completed modules) was associated with significantly greater reductions in pain and disability from pre-treatment to follow-up (d's = −0.57 and −0.38, P < 0.05). Parents, youth, and providers found treatment acceptable; providers had positive attitudes and demonstrated referrals over a maintenance period. Further research is needed to understand how to enhance treatment engagement with digital health interventions and optimize implementation.
Evaluation of Pathologic Response on Overall Survival After Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma
Authors: Sell Naomi M. , Lee Grace C. , Fernández-Del Castillo Carlos , Ferrone Cristina R. , Warshaw Andrew L. , Hong Theodore S. , Blaszkowsky Lawrence S. , Lillemoe Keith D. , Qadan Motaz 
Published: July 2020

Objectives
Single-institution studies have shown improved outcomes among patients with a pathologic complete response (pCR) following neoadjuvant therapy. We sought to evaluate the impact of pCR and near-complete response (nCR) on overall survival (OS) using a large national database.

Methods
The National Cancer Database was queried for patients given a diagnosis of pancreatic cancer from 2004 to 2014. A pCR was defined as no tumor identified in the pancreas after surgical resection. An nCR was defined as a primary tumor less than 1 cm without lymph node metastases. The primary outcome was OS.

Results
A total of 5364 patients underwent neoadjuvant chemotherapy and/or radiation followed by pancreatectomy. Forty-one patients (0.8%) had a pCR, 54 (1%) had an nCR, and the remaining 5266 (98.2%) had an otherwise incomplete response. Patients with pCR had a median OS of 43 months compared with 24 months for nCR and 23 months for incomplete response (P < 0.0001). Only pCR was associated with improved OS on adjusted Cox regression.

Conclusions
For patients given a diagnosis of pancreatic cancer who underwent neoadjuvant treatment and surgical resection, achieving a pCR was associated with improved OS compared with those with residual tumor. An association between nCR and improved survival was not observed.
Pancreatic Neuroendocrine Neoplasms and Gastrointestinal Stromal Tumors
Authors: Milanetto Anna Caterina , Pacciani Sabrina , Fassan Matteo , Pasquali Claudio 
Published: July 2020

Objective
Pancreatic neuroendocrine neoplasms (pNENs) and gastrointestinal stromal tumors (GISTs) represent rare neoplasms. Nonsyndromic cases of pNENs associated with a synchronous GIST were evaluated, and a review of the literature was performed.

Methods
We evaluated clinicopathologic features, postoperative outcome, and follow-up of patients operated on for nonsyndromic synchronous pNENs and GISTs in our unit (2003–2017).

Results
Five (3.2%) of 156 patients with a pNEN had an associated GIST (3 male/2 female; average age, 67 years). They were diagnosed with a pNEN preoperatively and underwent pancreatic surgery. In 4 patients, GISTs were detected intraoperatively. Histology showed 3 G1 and 2 G2 pNENs. All GISTs were low risk (median size, 0.9 cm). Two patients were alive without disease 108 and 132 months after surgery. In the literature, 7 cases were described. They had low-risk GISTs, with a gastric location in 6 cases (median size, 2.85 cm).

Conclusions
Sporadic pNENs coexisting with a GIST have been demonstrated in 12 cases. This association is considered fortuitous, and its true incidence may be underestimated. Surgery should be performed on the GIST during the pancreatic surgery. The prognosis strictly depends on the pancreatic NENs.
The Role of Laparoscopic Cholecystectomy After Severe and/or Necrotic Pancreatitis in the Setting of Modern Minimally Invasive Management of Pancreatic Necrosis
Authors: Ackermann Travis G. , Cashin Paul A. , Alwan Mostafa , Wewelwala Chamila C. , Tan Darius , Vu Anh N. , Bowers Kaye A. , Berry Roger , Croagh Daniel G. 
Published: July 2020

Objectives
The trend toward minimally invasive procedures (MIP) in necrotizing pancreatitis is increasing. The optimal timing and technique of cholecystectomy in severe/necrotizing pancreatitis is unclear. This study aims to determine the role of laparoscopic cholecystectomy after severe/necrotizing pancreatitis in the context of MIP.

Methods
Retrospective analysis of a prospective database was performed for consecutive patients after cholecystectomy for gallstone pancreatitis between January 2011 and January 2018 at Monash Health, Melbourne, Australia.

Results
Three hundred fifty-five patients with gallstone pancreatitis underwent laparoscopic cholecystectomy with 2 conversions. Patients with severe pancreatitis were older (P = 0.002), with a more even sex distribution when compared with mild pancreatitis. Females predominated in the mild pancreatitis group.
Patients with moderate/severe pancreatitis (P = 0.002) and necrosis (P > 0.001) were more likely to have delayed cholecystectomy compared with mild pancreatitis. There was no increase in biliary presentations while awaiting cholecystectomy. Length of stay for patients with severe/necrotizing pancreatitis (P = 0.001) was increased, surgical complications appeared similar.

Conclusions
Laparoscopic cholecystectomy can be performed safely and effectively for pancreatitis, irrespective of severity. The paradigm shift in the management of severe necrotizing pancreatitis away from open necrosectomy toward MIP can be extended to encompass laparoscopic cholecystectomy.
Continuous Video Monitoring
Authors: Abbe JacQualine Renee , O'Keeffe Christian 
Published: July 2020

Background:
Sitters are often used in the inpatient setting as a measure to ensure safety of patients with cognitive and behavioral concerns.

Problem:
Sitters are costly, and evidence is lacking that their presence produces safer outcomes. Continuous video monitoring is a safe alternative; yet, there is a lack of best practices and implementation strategies.

Approach:
A large academic medical center in the Pacific Northwest introduced continuous video monitoring as an adjunct measure to replace sitter use when appropriate. Adoption of the technology was influenced by nurse enculturation, leader standard work (standard parameters used by nurse leaders for process improvement), data tracking management, and patient/family feedback.

Outcomes:
Continuous video monitoring is a bridge for the nursing staff to enhance safety for patients and an additional safety intervention when sitter use is not reasonable.

Conclusion:
Utilizing technology such as continuous video monitoring can relieve sitters to allow for optimal productivity, increased safety, cost reduction, and nurse/family satisfaction.
A Roadmap for Practice-Based Evidence
Authors: Kaiser Jennifer , Wills Nicole , Reilly Therese , Pratt Jessica , Tumbleson Valerie , Niemeyer Marissa , Mindling Glenna 
Published: July 2020

Background:
To ensure successful integration and implementation of evidence into practice, validation of measures and interventions should be performed in the population and setting in which they will be used.

Purpose:
This article provides a method for evaluating the predictive performance of a risk tool using the Hester Davis fall risk tool as an example.

Methods:
A retrospective matched-pairs sample of fallers and nonfallers was created. Psychometric properties were calculated using 2 × 2 contingency tables and compared to data in the original report.

Results:
In this study sample, the risk tool showed minimal ability to distinguish patients at risk for falling from those not at risk.

Conclusions:
Organizations are urged to assess the performance of risk tools in their own patient population. This article provides a practical approach for the validation of evidence into the practice setting.
Time-to-Task Validation in Sequential Simulations as a Component of Nursing Student Competency
Authors: Shinnick Mary Ann 
Published: July 2020

Background
Time goals have not been tested as a component of nursing competence.

Methods
Using a known-groups approach, a multisite study was performed on prelicensure nursing students (novices) and experienced nurses (experts) who participated in 2 simulations of patient deterioration with time goals. Video capture was achieved with an eye tracker.

Results
While all novices did not achieve the time goals in both simulations, there was a significant improvement between the 2 simulations (P = .04). Experts were more successful in achieving the time-to-task goals in both simulations (44% and 95%, respectively). Statistical significance was found between the novice and expert groups in achieving the time goal for both simulations (P < .01).

Conclusions
This study was able to differentiate the expert group as being more proficient in a timed assessment, although the novices showed improvement between 2 simulations. This illustrates an opportunity for skill development among novices in managing patient deterioration amenable to time as an objective assessment.