bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimally Invasive Middle Fossa Keyhole Craniectomy for Repair of Superior Semicircular Canal Dehiscence
Authors: Trieu Vanessa , Pelargos Panayiotis E. , Spasic Marko , Chung Lawrance K. , Voth Brittany , Ung Nolan , Gopen Quinton , Yang Isaac 
Published: April 2017

Abstract

BACKGROUND: Superior semicircular canal dehiscence (SSCD) presents with varying degrees of auditory and vestibular dysfunction. The condition is confirmed on high-resolution computed tomography (CT) imaging, and symptoms are often improved by surgical repair. Although a classic middle fossa craniotomy has been used with good results, recent advances in technique have allowed for modification of the traditional approach into a smaller skin incision and a minimally invasive middle fossa keyhole craniectomy roughly 1.7 cm in diameter.

OBJECTIVE: To delineate this novel approach and describe the technique for accurate localization of the dehiscence using preoperative measurements and intraoperative image guidance, thereby minimizing the need for a larger skin incision and craniotomy.

METHODS: Patients were independently diagnosed with SSCD by the senior authors. Once relevant imaging was acquired, the novel keyhole technique was performed. Patients’ vestibular and auditory symptoms before and after the procedure were assessed. Outcomes from a series of patients treated with this keyhole approach were tabulated and reported.

RESULTS: Twelve cases from 11 patients were included in this series. Auditory symptoms had high rates of resolution with pulsatile tinnitus, internal amplification of sounds, and autophony being resolved in a majority of cases. Only 2 cases reported hearing decline. Sound/pressure induced vertigo and disequilibrium also demonstrated high rates of resolution. No complications were reported.

CONCLUSION: The minimally invasive middle fossa keyhole craniectomy is a novel approach for the repair of SSCD. This approach may contribute to resolved auditory and vestibular symptoms with low morbidity and quick recovery.
Trial Design and Endpoint Evaluation in Clinical Studies Addressing Chronic Back Pain
Authors: Staats Peter S. 
Published: April 2017

Study Design.
A review of the literature evaluating clinical trials of chronic back pain.

Objective.
To assist physicians in assessing the quality of clinical trial data to make the most informed treatment decisions.

Summary of Background Data.
Chronic pain is a tremendous public health issue, affecting close to 100 million adults in the United States, and costs the American people billions of dollars. One traditional treatment approach, the long-term use of opiate medications, has recently come under intense scrutiny for problems with complications, diversion, abuse, addiction, and lack of efficacy.
1
In addition, the Centers for Disease Control and Prevention has recognized that overprescribing opiates has enabled an overdose crisis, and written guidelines that are intended to limit their use. It is for this reason that physicians must have a comprehensive understanding of the range of drug-free alternative therapies available and have the tools needed to rigorously evaluate the chronic pain literature so they can make appropriate treatment decisions.

Methods.
An evaluation of how clinical trials are designed and ranked, outcome measures, and costs for a variety of therapies is necessary to determine which treatment option is the most efficacious for an individual patient.

Results.
Clinical trial data demonstrate that spinal cord stimulation (SCS) is a safe and effective treatment option for many types of chronic pain, including back pain. The last 10 years has brought tremendous advances in the field of neuromodulation. Today, several treatment modalities exist for SCS requiring the physician to be able to critically evaluate and interpret the literature and determine which modality has the strongest evidence. When evaluating clinical trial data of patients with chronic back pain, emphasis must be placed on well designed, randomized controlled trials with long-term follow-up producing level I evidence. These data are obtained in a rigorous manner and are likely to have less bias when compared with lower level studies.

Conclusion.
The level I studies performed to date have provided evidence that treatment with SCS results in sustainable pain reduction and improvements in scores measuring quality of life and patient functioning in those patients with chronic intractable back pain.

Level of Evidence: 5
A Contemporary Assessment of Acute Mechanical Ventilation in Beijing: Description, Costs, and Outcomes
Authors: Ye Yanping , Zhu Bo , Jiang Li , Jiang Qi , Wang Meiping , Hua Lin , Xi Xiuming 
Published: April 2017

Objective:
To evaluate the contemporary practice, outcomes, and costs related to mechanical ventilation among ICUs in China.

Design:
A prospective observational cohort study.

Setting:
Fourteen ICUs among 13 hospitals in Beijing, China.

Patients:
Seven hundred ninety-three patients who received at least 24 hours of mechanical ventilation within the first 48 hours of ICU stay.

Intervention:
None.

Measurements and results:
The mean age was 64 years. Sixty-three percent were male. New acute respiratory failure accounted for 85.5% of mechanical ventilation cases. Only 4.7% of the patients received mechanical ventilation for acute exacerbation of chronic obstructive pulmonary disease. The most widely used ventilation mode was the combination of synchronized intermittent mandatory ventilation and pressure support (43.6%). Use of lung-protective ventilation is widespread with tidal volumes of 7.1 mL/kg (2.1 mL/kg). The ICU/hospital mortality was 27.6%/29.3%, respectively (8.5%/9.7% for surgical patients and 41.3%/43.2% for medical patients, respectively). The mean level of ICU/hospital cost per patient was $15,271 (18,940)/$22,946 (25,575), respectively. The mean daily ICU cost per patient was $1,212.

Conclusion:
For the first time, we obtained a preliminary epidemiology data of mechanical ventilation in Beijing, China, through the study. Compared with the other nations, our patients are older, predominantly male, and treated according to prevailing international guidelines yet at a relatively high cost and high mortality. The expanding elderly population predicts increase demand for mechanical ventilation that must be met by continuous improvement in quality and efficiency of critical care services.
Do Concussive Symptoms Really Resolve in Young Children?
Authors: Bernard Coco O. , Ponsford Jennie L. , McKinlay Audrey , McKenzie Dean , Krieser David 
Published: April 2017

Objectives:
To examine the frequency and nature of postconcussive symptoms (PCSs) and behavioral outcomes in young children following mild traumatic brain injury (mTBI) or concussion.

Setting:
Emergency department.

Participants:
Children aged 2 to 12 years presenting with either a concussion or minor bodily injury (control).

Outcome Measurement:
Parent ratings of PCS were obtained within 72 hours of injury, at 1 week, and 1, 2, and 3 months postinjury using a comprehensive PCS checklist. Preinjury behavior was examined at baseline using the Clinical Assessment of Behavior, which was readministered 1 and 3 months postinjury.

Results:
PCS burden following mTBI peaked in the acute phase postinjury but reduced significantly from 1 week to 1 month postinjury. Parents of children with mTBI reported more persistent PCSs up to 3 months postinjury than trauma controls, characterized mostly by behavioral and sleep-related symptoms. Subtle increases in problematic behaviors were observed from baseline (preinjury) to 1 month postinjury and persisted at 3 months postinjury; however, scores were not classified as clinically “at risk.”

Conclusions:
A significant minority of young children experienced persistent PCS and problematic behavior following mTBI. Care must be taken when assessing PCS in younger children as method of PCS assessment may influence parental reporting.
Impact of Telephone-Based Problem-Solving Treatment on the Use of Medical and Psychological Services in the Military
Authors: Richardson John S. , Fann Jesse R. , Bell Kathleen R. , Temkin Nancy 
Published: April 2017

Objective:
To explore the impact of problem-solving treatment (PST) for mild traumatic brain injury in active duty service members on the use of medical and psychological services.

Participants:
Service members who had a mild traumatic brain injury during their last deployment and enrolled in the CONcussion Treatment After Combat Trauma (CONTACT) study.

Design:
Secondary analysis of a randomized clinical trial. Participants were assigned to telephone-based PST, or e-mailed or mailed education only over the course of 6 months.

Main Measure:
Self-reported health service utilization from months 4 through 6 and 10 through 12 after initiation of treatment, using the Cornell Service Index.

Results:
In months 4 to 6, participants receiving PST had 6.17 times the odds of an emergency department visit or hospitalization than those receiving education only (95% confidence interval = 1.92–19.8; P value = .0023). These estimates, however, were not significant using a conservative Bonferroni correction (P value threshold < .0014). There were no other significant differences for other medical or psychological services received in months 4 to 6 or 10 to 12.

Conclusion:
Telephone-based PST was designed to complement clinical care, and this study showed that it may increase emergency department utilization. Future evaluations of PST with more accurate and complete measures of health service utilization are needed.
Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study
Authors: Baker-Sparr Christina , Hart Tessa , Bergquist Thomas , Bogner Jennifer , Dreer Laura , Juengst Shannon , Mellick David , O'Neil-Pirozzi Therese M. , Sander Angelle M. , Whiteneck Gale G. 
Published: April 2017

Objectives:
To characterize Internet and social media use among adults with moderate to severe traumatic brain injury (TBI) and to compare demographic and socioeconomic factors associated with Internet use between those with and without TBI.

Setting:
Ten Traumatic Brain Injury Model Systems centers.

Participants:
Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems National Database and eligible for follow-up from April 1, 2014, to March 31, 2015.

Design:
Prospective cross-sectional observational cohort study.

Main Measures:
Internet usage survey.

Results:
The proportion of Internet users with TBI was high (74%) but significantly lower than those in the general population (84%). Smartphones were the most prevalent means of Internet access for persons with TBI. The majority of Internet users with TBI had a profile account on a social networking site (79%), with more than half of the sample reporting multiplatform use of 2 or more social networking sites.

Conclusion:
Despite the prevalence of Internet use among persons with TBI, technological disparities remain in comparison with the general population. The extent of social media use among persons with TBI demonstrates the potential of these platforms for social engagement and other purposes. However, further research examining the quality of online activities and identifying potential risk factors of problematic use is recommended.
Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model
Authors: Villarnovo Dania , McCleary-Wheeler Angela L. , Richards Kristy L. 
Published: April 2017

Purpose of review
Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model.

Recent findings
The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies. Research in this field has focused on filling in the gaps to make the canine lymphoma model more robust. These advances have included work on biomarkers, detection of minimal residual disease, expansion of genomic and proteomic data, and immunotherapy.

Summary
Incorporating pet dogs into the drug development pipeline can improve the efficiency and predictability of preclinical models and decrease the time and cost required for a therapeutic target to be translated into clinical benefit.
US antibiotic stewardship and penicillin allergy
Authors: Wada Kara J. , Calhoun Karen H. 
Published: April 2017

Purpose of review
The purpose of this review is to improve otolaryngologists’ antibiotic stewardship by detailing current approaches to penicillin allergy.

Recent findings
Although up to 15% of hospitalized patients in the United States have a penicillin allergy recorded on their charts, fewer than 10% of these have a true penicillin allergy.

Summary
Using a combination of a detailed allergy history, skin testing and graded-dose administration, many patients whose charts say ‘penicillin-allergic’ can safely be treated with penicillin and cross-reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves money.
NetREX: Network Rewiring using EXpression - Towards Context Specific Regulatory Networks
Authors: Wang Yijie , Cho Dong-Yeon , Lee Hangnoh , Fear Justin , Oliver Brian , Przytycka Teresa M 
Published: April 2017

AbstractUnderstanding gene regulation is a fundamental step towards understanding of how cells function and respond to environmental cues and perturbations. An important step in this direction is the ability to infer the transcription factor (TF)-gene regulatory network (GRN). However gene regulatory networks are typically constructed disregarding the fact that regulatory programs are conditioned on tissue type, developmental stage, sex, and other factors. Due to lack of the biological context specificity, these context-agnostic networks may not provide insight for revealing the precise actions of genes for a specific biological system under concern. Collecting multitude of features required for a reliable construction of GRNs such as physical features (TF binding, chromatin accessibility) and functional features (correlation of expression or chromatin patterns) for every context of interest is costly. Therefore we need methods that is able to utilize the knowledge about a context-agnostic network (or a network constructed in a related context) for construction of a context specific regulatory network.To address this challenge we developed a computational approach that utilizes expression data obtained in a specific biological context such as a particular development stage, sex, tissue type and a GRN constructed in a different but related context (alternatively an incomplete or a noisy network for the same context) to construct a context specific GRN. Our method, NetREX, is inspired by network component analysis (NCA) that estimates TF activities and their influences on target genes given predetermined topology of a TF-gene network. To predict a network under a different condition, NetREX removes the restriction that the topology of the TF-gene network is fixed and allows for adding and removing edges to that network. To solve the corresponding optimization problem, which is non-convex and non-smooth, we provide a general mathematical framework allowing use of the recently proposed Proximal Alternative Linearized Maximization technique and prove that our formulation has the properties required for convergence.We tested our NetREX on simulated data and subsequently applied it to gene expression data in adult females from 99 hemizygotic lines of theDrosophiladeletion (DrosDel) panel. The networks predicted by NetREX showed higher biological consistency than alternative approaches. In addition, we used the list of recently identified targets of the Doublesex (DSX) transcription factor to demonstrate the predictive power of our method.
Evaluation of pre-analytical factors affecting plasma DNA analysis
Authors: Markus Havell , Contente-Cuomo Tania , Liang Winnie S. , Borad Mitesh J. , Sivakumar Shivan , Gollins Simon , Tran Nhan L. , Dhruv Harshil D. , Berens Michael E. , Bryce Alan , Sekulic Aleksandar , Ribas Antoni , Trent Jeffrey M. , LoRusso Patricia M. , Murtaza Muhammed 
Published: April 2017

AbstractPre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci (mean amplicon size: 71 bp and 471 bp respectively). Using this assay, we compared performance of 7 cfDNA extraction kits and found cfDNA yield and fragment size varies significantly between them. We also compared 3 blood collection protocols used to collect plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA BCT tubes at ambient temperature processed within 24 hours and 72 hours of collection). To assess whether cell-stabilizing preservative in BCT tubes introduced noise in cfDNA, we performed digital targeted sequencing. We found no significant differences in cfDNA yield, fragment size and background sequencing noise between these protocols. In 219 clinical samples tested for quality using the ddPCR assay, cfDNA fragment size was significantly shorter in plasma samples immediately processed for ctDNA analysis compared to archived samples, suggesting background DNA contributed by lysed peripheral blood cells. In summary, we describe a multiplexed ddPCR approach that enables cfDNA quality assessment and could inform the design of future circulating tumor DNA studies.Gene namesNone
Highly efficient DNA-free gene disruption in the agricultural pestCeratitis capitataby CRISPR-Cas9 RNPs
Authors: Meccariello Angela , Monti Simona Maria , Romanelli Alessandra , Colonna Rita , Primo Pasquale , Inghilterra Maria Grazia , Del Corsano Giuseppe , Ramaglia Antonio , Iazzetti Giovanni , Chiarore Antonia , Patti Francesco , Heinze Svenia D. , Salvemini Marco , Lindsay Helen , Chiavacci Elena , Burger Alexa , Robinson Mark D. , Mosimann Christian , Bopp Daniel , Saccone Giuseppe 
Published: April 2017

ABSTRACTThe Mediterranean fruitflyCeratitis capitata(medfly) is an invasive agricultural pest of high economical impact and has become an emerging model for developing new genetic control strategies as alternative to insecticides. Here, we report the successful adaptation of CRISPR-Cas9-based gene disruption in the medfly by injectingin vitropre-assembled, solubilized Cas9 ribonucleoprotein complexes (RNPs) loaded with gene-specific sgRNAs into early embryos. When targeting the eye pigmentation genewhite eye(we), we observed a high rate of somatic mosaicism in surviving G0 adults. Germline transmission of mutatedwealleles by G0 animals was on average above 70%, with individual cases achieving a transmission rate of nearly 100%. We further recovered large deletions in thewegene when two sites were simultaneously targeted by two sgRNAs. CRISPR-Cas9 targeting of theCeratitisortholog of theDrosophilasegmentationpairedgene (Ccprd) caused segmental malformations in late embryos and in hatched larvae. Mutant phenotypes correlate with repair by non-homologous end joining (NHEJ) lesions in the two targeted genes. This simple and highly effective Cas9 RNP-based gene editing to introduce mutations inCeratitis capitatawill significantly advance the design and development of new effective strategies for pest control management.
Autogenous cross-regulation ofQuakingmRNA processing and translation balancesQuakingfunctions in splicing and translation
Authors: Fagg W. Samuel , Ares Manuel 
Published: April 2017

AbstractQuaking RNA binding protein (RBP) isoforms arise from a singleQuakinggene, and bind the same RNA motif to regulate splicing, stability, decay, and localization of a large set of RNAs. However, the mechanisms by which the expression of this single gene is controlled to distribute appropriate amounts of eachQuakingisoform to regulate such disparate gene expression processes are unknown. Here we explore the separate mechanisms that regulate expression of two isoforms, Quaking-5 (Qk5) and Quaking-6 (Qk6), in mouse muscle cells. We first demonstrate that Qk5 and Qk6 proteins have distinct functions in splicing and translation respectively, enforced primarily through differential subcellular localization. Using isoform-specific depletion, we find both Qk5 and Qk6 act throughcisandtranspost-transcriptional regulatory mechanisms on their own and each other’s transcripts, creating a network of auto- and cross-regulatory controls. Qk5 has a major role in nuclear RNA stability and splicing, whereas Qk6 acts through translational regulation. In different cell types the cross-regulatory influences discovered here generate a spectrum of Qk5/Qk6 ratios subject to additional cell type and developmental controls. These unexpectedly complex feedback loops underscore the importance of the balance of Qk isoforms, especially where they are key regulators of development and cancer.
ConsensusDriver improves upon individual algorithms for predicting driver alterations in different cancer types and individual patients – a toolbox for precision oncology
Authors: Bertrand Denis , Drissler Sibyl , Chia Burton , Koh Jia Yu , Chenhao Li , Suphavilai Chayaporn , Tan Iain Beehuat , Nagarajan Niranjan 
Published: April 2017

AbstractBackgroundIn recent years, several large-scale cancer genomics studies have helped generate detailed molecular profiling datasets for many cancer types and thousands of patients. These datasets provide a unique resource for studying cancer driver prediction methods and their utility for precision oncology, both to predict driver genetic alterations in patient subgroups (e.g. defined by histology or clinical phenotype) or even individual patients.MethodsWe performed the most comprehensive assessment to date of 18 driver gene prediction methods, on more than 3,400 tumour samples, from 15 cancer types, to determine their suitability in guiding precision medicine efforts. These methods have diverse approaches, which can be classified into five categories:functionalimpact on proteins in general (FI) or specific tocancer (FIC),cohort-basedanalysis for recurrent mutations (CBA),mutations withexpressioncorrelation (MEC) and methods that use geneinteractionnetwork-basedanalysis (INA).ResultsThe performance of driver prediction methods varies considerably, with concordance with a gold-standard varying from 9% to 68%. FI methods show relatively poor performance (concordance <22%) while CBA methods provide conservative results, but require large sample sizes for high sensitivity. INA methods, through the integration of genomic and transcriptomic data, and FIC methods, by training cancer-specific models, provide the best trade-off between sensitivity and specificity. As the methods were found to predict different subsets of drivers, we propose a novel consensus-based approach, ConsensusDriver, which significantly improves the quality of predictions (20% increase in sensitivity). This tool can be applied to predict driver alterations in patient subgroups (e.g. defined by histology or clinical phenotype) or even individual patients.ConclusionExisting cancer driver prediction methods are based on very different assumptions and each of them can only detect a particular subset of driver events. Consensus-based methods, like ConsensusDriver, are thus a promising approach to harness the strengths of different driver prediction paradigms.